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Adults with high cholesterol taking statins may have a significantly higher risk of developing glaucoma than those not taking the cholesterol-lowering drugs, an observational study of a large research database found.

The study, published in Ophthalmology Glaucoma, analyzed electronic health records of 79,742 adults with hyperlipidemia in the All of Us Research Program database from 2017 to 2022. The repository is maintained by the National Institutes of Health and provides data for research into precision medicine.

The 6365 statin users in the study population had a 47% greater unadjusted prevalence of glaucoma than nonusers of the drugs (P < .001) and a 13% greater prevalence in models that adjusted for potential confounding variables (P = .02). The researchers also found statin users had significantly higher levels of low-density lipoprotein cholesterol (LDL-C), but even patients with optimal levels of LDL-C had higher rates of glaucoma.

 

‘A Little Unusual’

Drawing any clinically relevant conclusions from this latest study would be premature, said Victoria Tseng, MD, PhD, an assistant professor at UCLA Stein Eye Institute and Doheny Eye Centers UCLA, and the senior author of the study. “I certainly would not be telling my patients on statins to stop their statins.”

Tseng acknowledged her group’s finding runs counter to previous studies that found statins may help prevent glaucoma or at least have no effect on the eye disease, although the association between cholesterol and glaucoma has been well established.

A 2019 analysis of nearly 137,000 participants in three population studies found no connection between statin use and the risk for primary open-angle glaucoma. A 2012 study of more than 500,000 people with high cholesterol found statin use was associated with a significant reduction in the risk for open-angle glaucoma.

“It’s a little unusual that we found the opposite,” Tseng said in an interview.

One explanation is the observational nature of the AoU analysis Tseng’s group conducted. “We don’t know what these people look like or how well the data were collected, so we’re going off of what’s there in the database,” she said.

Another explanation could be the nature of hyperlipidemia itself, she said. “There have definitely been studies that suggest increased cholesterol levels are associated with an increased risk of glaucoma. Presumably, you’re not going to be taking a statin unless your cholesterol is a little worse.”

While the study analysis attempted to control for cholesterol levels, Tseng noted, “there could be some residual confounding from that.”

Statin users in the study had an average LDL-C level of 144.9 mg/dL vs 136.3 mg/dL in the population not taking any cholesterol medication (P < .001). Statin users with optimal LDL-C, defined as less than 100 mg/dL, had a 39% greater adjusted prevalence of glaucoma (P = .02), while those with high LDL-C (160-189 mg/dL) had a 37% greater adjusted prevalence (P = .005).

Age was another factor in the risk for glaucoma, the study found. Statin users aged 60-69 years had an adjusted rate of glaucoma 28% greater than that for nonusers (P = .05).

Laboratory studies may help clarify the relationships between statins and glaucoma, Tseng said. That could include putting statins directly on the optic nerve of laboratory mice and further investigating how statins affect the mechanisms that influence eye pressure, a key driver of glaucoma. From a population study perspective, a randomized trial of glaucoma patients comparing the effect of statins and other cholesterol-lowering medications with nonuse may provide answers.

 

Database Strengths and Limitations

The study “adds to the somewhat mixed literature on the potential association between statins and glaucoma,” Sophia Wang, MD, MS, a glaucoma specialist at Stanford Byers Eye Institute in Palo Alto, California, said in an interview.

The AoU research cohort is a “notable strength” of the new paper, added Wang, who has used the AoU database to study the relationship between blood pressure, blood pressure medications, and glaucoma.

“The population is especially large and diverse, with a large proportion of participants from backgrounds that are traditionally underrepresented in research,” she said. And The inclusion of both medical records and survey data means the health information on the cohort is detailed and longitudinal.

“The authors make excellent use here of the data by including in their analyses results of laboratory investigations — LDL-C, notably — which wouldn’t be readily available in other types of datasets such as claims datasets,” she said.

However, the database has limitations as well, including its reliance on coding, which is prone to errors, to determine glaucoma diagnosis and missing information on eye examinations. In addition, the study used one LDL-C measurement rather than multiple measurements, Wang pointed out, “and we know that LDL-C can vary over time.”

The study was funded by Research to Prevent Blindness. Tseng and Wang reported no relevant financial relationships to disclose.

A version of this article first appeared on Medscape.com.

Adults with high cholesterol taking statins may have a significantly higher risk of developing glaucoma than those not taking the cholesterol-lowering drugs, an observational study of a large research database found.

The study, published in Ophthalmology Glaucoma, analyzed electronic health records of 79,742 adults with hyperlipidemia in the All of Us Research Program database from 2017 to 2022. The repository is maintained by the National Institutes of Health and provides data for research into precision medicine.

The 6365 statin users in the study population had a 47% greater unadjusted prevalence of glaucoma than nonusers of the drugs (P < .001) and a 13% greater prevalence in models that adjusted for potential confounding variables (P = .02). The researchers also found statin users had significantly higher levels of low-density lipoprotein cholesterol (LDL-C), but even patients with optimal levels of LDL-C had higher rates of glaucoma.

 

‘A Little Unusual’

Drawing any clinically relevant conclusions from this latest study would be premature, said Victoria Tseng, MD, PhD, an assistant professor at UCLA Stein Eye Institute and Doheny Eye Centers UCLA, and the senior author of the study. “I certainly would not be telling my patients on statins to stop their statins.”

Tseng acknowledged her group’s finding runs counter to previous studies that found statins may help prevent glaucoma or at least have no effect on the eye disease, although the association between cholesterol and glaucoma has been well established.

A 2019 analysis of nearly 137,000 participants in three population studies found no connection between statin use and the risk for primary open-angle glaucoma. A 2012 study of more than 500,000 people with high cholesterol found statin use was associated with a significant reduction in the risk for open-angle glaucoma.

“It’s a little unusual that we found the opposite,” Tseng said in an interview.

One explanation is the observational nature of the AoU analysis Tseng’s group conducted. “We don’t know what these people look like or how well the data were collected, so we’re going off of what’s there in the database,” she said.

Another explanation could be the nature of hyperlipidemia itself, she said. “There have definitely been studies that suggest increased cholesterol levels are associated with an increased risk of glaucoma. Presumably, you’re not going to be taking a statin unless your cholesterol is a little worse.”

While the study analysis attempted to control for cholesterol levels, Tseng noted, “there could be some residual confounding from that.”

Statin users in the study had an average LDL-C level of 144.9 mg/dL vs 136.3 mg/dL in the population not taking any cholesterol medication (P < .001). Statin users with optimal LDL-C, defined as less than 100 mg/dL, had a 39% greater adjusted prevalence of glaucoma (P = .02), while those with high LDL-C (160-189 mg/dL) had a 37% greater adjusted prevalence (P = .005).

Age was another factor in the risk for glaucoma, the study found. Statin users aged 60-69 years had an adjusted rate of glaucoma 28% greater than that for nonusers (P = .05).

Laboratory studies may help clarify the relationships between statins and glaucoma, Tseng said. That could include putting statins directly on the optic nerve of laboratory mice and further investigating how statins affect the mechanisms that influence eye pressure, a key driver of glaucoma. From a population study perspective, a randomized trial of glaucoma patients comparing the effect of statins and other cholesterol-lowering medications with nonuse may provide answers.

 

Database Strengths and Limitations

The study “adds to the somewhat mixed literature on the potential association between statins and glaucoma,” Sophia Wang, MD, MS, a glaucoma specialist at Stanford Byers Eye Institute in Palo Alto, California, said in an interview.

The AoU research cohort is a “notable strength” of the new paper, added Wang, who has used the AoU database to study the relationship between blood pressure, blood pressure medications, and glaucoma.

“The population is especially large and diverse, with a large proportion of participants from backgrounds that are traditionally underrepresented in research,” she said. And The inclusion of both medical records and survey data means the health information on the cohort is detailed and longitudinal.

“The authors make excellent use here of the data by including in their analyses results of laboratory investigations — LDL-C, notably — which wouldn’t be readily available in other types of datasets such as claims datasets,” she said.

However, the database has limitations as well, including its reliance on coding, which is prone to errors, to determine glaucoma diagnosis and missing information on eye examinations. In addition, the study used one LDL-C measurement rather than multiple measurements, Wang pointed out, “and we know that LDL-C can vary over time.”

The study was funded by Research to Prevent Blindness. Tseng and Wang reported no relevant financial relationships to disclose.

A version of this article first appeared on Medscape.com.

Adults with high cholesterol taking statins may have a significantly higher risk of developing glaucoma than those not taking the cholesterol-lowering drugs, an observational study of a large research database found.

The study, published in Ophthalmology Glaucoma, analyzed electronic health records of 79,742 adults with hyperlipidemia in the All of Us Research Program database from 2017 to 2022. The repository is maintained by the National Institutes of Health and provides data for research into precision medicine.

The 6365 statin users in the study population had a 47% greater unadjusted prevalence of glaucoma than nonusers of the drugs (P < .001) and a 13% greater prevalence in models that adjusted for potential confounding variables (P = .02). The researchers also found statin users had significantly higher levels of low-density lipoprotein cholesterol (LDL-C), but even patients with optimal levels of LDL-C had higher rates of glaucoma.

 

‘A Little Unusual’

Drawing any clinically relevant conclusions from this latest study would be premature, said Victoria Tseng, MD, PhD, an assistant professor at UCLA Stein Eye Institute and Doheny Eye Centers UCLA, and the senior author of the study. “I certainly would not be telling my patients on statins to stop their statins.”

Tseng acknowledged her group’s finding runs counter to previous studies that found statins may help prevent glaucoma or at least have no effect on the eye disease, although the association between cholesterol and glaucoma has been well established.

A 2019 analysis of nearly 137,000 participants in three population studies found no connection between statin use and the risk for primary open-angle glaucoma. A 2012 study of more than 500,000 people with high cholesterol found statin use was associated with a significant reduction in the risk for open-angle glaucoma.

“It’s a little unusual that we found the opposite,” Tseng said in an interview.

One explanation is the observational nature of the AoU analysis Tseng’s group conducted. “We don’t know what these people look like or how well the data were collected, so we’re going off of what’s there in the database,” she said.

Another explanation could be the nature of hyperlipidemia itself, she said. “There have definitely been studies that suggest increased cholesterol levels are associated with an increased risk of glaucoma. Presumably, you’re not going to be taking a statin unless your cholesterol is a little worse.”

While the study analysis attempted to control for cholesterol levels, Tseng noted, “there could be some residual confounding from that.”

Statin users in the study had an average LDL-C level of 144.9 mg/dL vs 136.3 mg/dL in the population not taking any cholesterol medication (P < .001). Statin users with optimal LDL-C, defined as less than 100 mg/dL, had a 39% greater adjusted prevalence of glaucoma (P = .02), while those with high LDL-C (160-189 mg/dL) had a 37% greater adjusted prevalence (P = .005).

Age was another factor in the risk for glaucoma, the study found. Statin users aged 60-69 years had an adjusted rate of glaucoma 28% greater than that for nonusers (P = .05).

Laboratory studies may help clarify the relationships between statins and glaucoma, Tseng said. That could include putting statins directly on the optic nerve of laboratory mice and further investigating how statins affect the mechanisms that influence eye pressure, a key driver of glaucoma. From a population study perspective, a randomized trial of glaucoma patients comparing the effect of statins and other cholesterol-lowering medications with nonuse may provide answers.

 

Database Strengths and Limitations

The study “adds to the somewhat mixed literature on the potential association between statins and glaucoma,” Sophia Wang, MD, MS, a glaucoma specialist at Stanford Byers Eye Institute in Palo Alto, California, said in an interview.

The AoU research cohort is a “notable strength” of the new paper, added Wang, who has used the AoU database to study the relationship between blood pressure, blood pressure medications, and glaucoma.

“The population is especially large and diverse, with a large proportion of participants from backgrounds that are traditionally underrepresented in research,” she said. And The inclusion of both medical records and survey data means the health information on the cohort is detailed and longitudinal.

“The authors make excellent use here of the data by including in their analyses results of laboratory investigations — LDL-C, notably — which wouldn’t be readily available in other types of datasets such as claims datasets,” she said.

However, the database has limitations as well, including its reliance on coding, which is prone to errors, to determine glaucoma diagnosis and missing information on eye examinations. In addition, the study used one LDL-C measurement rather than multiple measurements, Wang pointed out, “and we know that LDL-C can vary over time.”

The study was funded by Research to Prevent Blindness. Tseng and Wang reported no relevant financial relationships to disclose.

A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity. 

Michelle L. O’Donoghue, MD, MPH: I’m here at the American Heart Association Scientific Sessions. It’s a very exciting meeting, but one of the interesting topics that we’re going to be talking about is lipoprotein(a) [Lp(a)] . It’s definitely one of the hottest sessions of the meeting.

Joining me to discuss this topic is Dr Steve Nicholls, who is arguably one of the leading experts in the world on lipids. He’s a professor of medicine at Monash University in Australia. Welcome. Thanks, Steve. 

Stephen J. Nicholls, MBBS, PhD: Thanks for having me. 

O’Donoghue: There are two phase 2 studies that we’ll circle back to that are being presented here at the American Heart Association meeting. These are for novel therapeutics that lower Lp(a). Perhaps taking a step back, we know that there’s a large body of evidence to support the concept that Lp(a) plays a causal role in heart disease and atherogenesis, but to date we haven’t had any effective therapies to really lower it.

Thinking about the therapeutics specifically that are on the horizon, perhaps we could start there. Which one is furthest along in development, and how does that look in terms of its ability to lower Lp(a)?

 

Pelacarsen, an ASO

Nicholls: Most of the therapies are injectable. Most of them are nucleic acid–based therapies, and the one that’s most advanced is an agent called pelacarsen. Pelacarsen is an antisense oligonucleotide (ASO), and it has gone all the way through its early phase 2 studies. It has a fully enrolled cardiovascular outcome trial.

We’re all eagerly awaiting the results of that study sometime in the next year or so. That will be the first large-scale clinical trial that will give us some clinical validation to ask the question of whether substantive lowering of Lp(a) will lower cardiovascular risk, with an agent that in early studies looks like it lowers Lp(a) about 80%.

O’Donoghue: Which is tremendous, because again, we really don’t have any effective therapies right now. I guess one of the big questions is, how much do we need to lower Lp(a) for that to translate into meaningful clinical benefit? What’s your sense there? 

Nicholls: Well, we simply don’t know. We’ve tried to look to genetics to try and give us some sort of sense in terms of what that looks like. Lp(a) is a little tricky because the assays and the numbers that get spit out can be tricky in terms of trying to compare apples and apples in different studies. 

We think that it’s probably at least a 50- to 75-mg/dL lowering of Lp(a) using the old units. We think that pelacarsen would hit that, and so our hope is that that would translate to a 15%-20% reduction in major cardiovascular events, but again, we’ve never asked this question before. 

We have data from PCSK9 inhibitor trials showing that lesser reductions in Lp(a) of 25%-30% with both evolocumab and alirocumab contributed to the clinical benefit that we saw in those studies. Those agents were really good at lowering low-density lipoprotein (LDL) cholesterol, but Lp(a) lowering seemed to matter. One would be very hopeful that if a 25%-30% lowering of Lp(a) is useful, then an 80% or greater lowering of Lp(a) should be really useful. 

 

The siRNAs

O’Donoghue: In addition to the ASO pelacarsen that you mentioned, there are several therapeutics in the pipeline, including three small interfering (si) RNAs that are at least in phase 2 and phase 3 testing at this point in time. There’s olpasiran, which in phase 2 testing led to more than a 95% reduction in Lp(a), and then lepodisiran , which has now moved into phase 3  testing, albeit we haven’t seen yet the phase 2  results. 

What is your sense of lepodisiran and its efficacy? 

Nicholls: What’s been really quite striking about the siRNAs is the even more profound degree of lowering of Lp(a) that we’re seeing. We’re seeing 90% and greater lowering of Lp(a) in all of those programs. We’re seeing some differences between the programs in terms of the durability of that effect. 

I think it would be fair to say that with zerlasiran we’re starting to see perhaps that lowering effect starts to taper off a little bit more quickly than the other two. I think that may have some implications in terms of what dosing regimens may look like in the future. 

Even so, we’re talking about therapies that may be dosed 3- to 6-monthly, or even with the potential for being less frequent than that with lepodisiran. Again, I think the phase 2 data will be really important in terms of giving us more information.

O’Donoghue: For the lepodisiran results, I was really quite struck that even though it was small numbers, single dose administered, it really looked like the duration of effect persisted at the higher doses up to about a year. 

Nicholls: It looks pretty promising. We’ve launched the ACCLAIM study, the large cardiovascular outcome trial of lepodisiran, with a 6-monthly regimen. We are hopeful that more information may be able to give us the opportunity for even less frequent administration. 

That has really important implications for patients where adherence is a particular issue. They may just simply want to come into the clinic. You know, once or twice a year, very much like we’re seeing with inclisiran, and that may be a really effective approach for many patients. 

O’Donoghue: You alluded to the zerlasiran results, which were presented here at the American Heart Association meeting, and that even though it led to a robust reduction in Lp(a), it looked like the durability component was maybe a little bit shorter than for some of the other siRNAs that are currently being evaluated.

What’s your sense of that? 

Nicholls: It probably is. The implications clinically, at least in an outcome trial when they ultimately get to that point, probably aren’t that important. They’ll probably just have slightly more frequent administration. That may become a bigger issue when it gets out into the clinic.

The nice thing is that if all of these agents appear to be effective, are well tolerated, and get out to the clinic, then clinicians and patients are going to have a lot of choice. 

O’Donoghue: I think more competition is always good news for the field, ultimately. I think to your point, especially for a drug that might be self-administered, ultimately, whether it’s once a month or once every 3 months, it doesn’t probably make much difference. I think different choices are needed for different patients. 

Perhaps that’s a perfect segue to talk about the oral Lp(a) inhibitor that is also being developed. You presented these results for muvalaplin. 

 

Muvalaplin, an Oral Small Molecule

Nicholls: In terms of frequency of administration, we’re talking about a daily oral therapeutic. For patients who don’t want an injectable and are happy to take a tablet every day, muvalaplin has the potential to be a really good option for them. 

Muvalaplin is an oral small-molecule inhibitor. It essentially prevents apolipoprotein(a) [apo(a)] from binding to apolipoprotein B (apo B). We presented phase 1 data  at the European Society of Cardiology meeting last year, showing probably Lp(a) lowering on the order of about 65%. Here, we’re going to show that that’s a little bit more. It looks like it’s probably at least 70% lowering using a standard Lp(a) assay. Using an assay that looks specifically at intact Lp(a) particles, it’s probably well in excess of 80%.

Those are really good results. The safety and tolerability with muvalaplin look really good. Again, we’ll need to see that agent move forward into a large outcome trial and we’ve yet to hear about that, at least for now. 

O’Donoghue: It’s an interesting challenge that you faced in terms of the assay because, as you say, it really disrupts the apo(a) from binding to the apo B particle, and hence, a traditional assay that just measures apo(a), regardless of whether or not it’s bound to an apo B particle, may be a conservative estimate.

Nicholls: It may, in particular, because we know that apo(a) ultimately then binds to the drug. That assay is measuring what we think is nonfunctional apo(a) in addition to functional apo(a). It’s measuring functional apo(a) that’s still on an actual Lp(a) particle, but if it’s bound to muvalaplin, we think to some degree that’s probably unfair to count that. That’s why trying to develop other assays to try and understand the full effect of the drug is really important in terms of trying to understand how we develop that and move that forward.

O’Donoghue: Is there any evidence yet that the apo(a) particle that is not bound to apo B is in fact nonfunctional as you described it? 

Nicholls: We think that’s likely to be the case, but I think there continues to be research in that space to try and settle that question once and for all. 

O’Donoghue: Again, I think it’s a really exciting time in this field. Right now, we have three ongoing phase 3 trials. We have the pelacarsen trial that is still in follow-up, and fingers crossed, maybe will report out next year. Olpasiran is also in phase 3 testing, completed enrollment, and also is in the follow-up period. We also have lepodisiran, the ACCLAIM trial, as you mentioned. For people who are perhaps watching and looking to enroll their patients, this trial is still ongoing right now in terms of enrollment. 

Nicholls: It is, and what’s nice about the ACCLAIM study is that it includes both primary and secondary prevention patients. For the first time in a big outcome trial, patients with high Lp(a) levels but who have yet to have a clinical event can actually get into a clinical trial.

I’m sure, like you, my clinic is full of patients with high Lp(a) who are really desperate to get into these trials. Many of those primary prevention patients just simply haven’t qualified, so that’s really good news. 

The step beyond that, if we’re talking about even less frequent administration, is gene editing. We’re seeing those studies with CRISPR move forward to try to evaluate whether a single gene-editing approach at Lp(a) will be all that you need, which is even a more amazing concept, but that’s a study that needs more work. 

O’Donoghue: An exciting space though, for sure. As a final thought, you mentioned the patients in your clinic who you have identified as having high Lp(a). What are you doing right now in your practice for managing those patients? I think there are many practitioners out there who struggle with whether they should really measure their patients’ Lp(a), and whether they want to know that information.

Nicholls: Yeah, it’s really hard. The answer is yes, we do want to know it. We know it’s a great risk enhancer. We know that a patient with a high Lp(a) is somebody whom I want to more intensively treat their other risk factors. I’m aiming for a lower LDL. I’m being much tighter with blood pressure control.

I think there’s some argument from observational data at least that aspirin remains a consideration, particularly in patients where you think there’s a particularly high risk associated with that high Lp(a). I think there are things we absolutely can do today, but we can’t do anything if you don’t know the numbers.

It starts with testing, and then we can move on to what we can do today, and then hopefully in the not-too-distant future, we’ll have specific therapies that really enable for us to address Lp(a) quite definitively. 

O’Donoghue: Thanks again for taking the time. This was a very helpful discussion.

 

Michelle O’Donoghue is a cardiologist at Brigham and Women’s Hospital and senior investigator with the TIMI Study Group. A strong believer in evidence-based medicine, she relishes discussions about the published literature. A native Canadian, Michelle loves spending time outdoors with her family but admits with shame that she’s never strapped on hockey skates. Dr O’Donoghue, Senior Investigator, TIMI Study Group; Associate Professor of Medicine, Harvard Medical School; Associate Physician, Brigham and Women’s Hospital, Boston, Massachusetts, disclosed ties to Janssen; Novartis; CVS Minute Clinic; Merck & Co.; GlaxoSmithKline; Eisai Inc.; AstraZeneca Pharmaceuticals LP; Janssen Pharmaceuticals; Medicines Company; and Amgen. The opinions expressed in this article do not necessarily reflect the views and opinions of Brigham and Women’s Hospital. Stephen J. Nicholls, MBBS, PhD, Director, Victorian Heart Institute, Monash University; Director, Victorian Heart Hospital, Monash Health, Melbourne, Australia, has disclosed ties with Akcea Therapeutics; Amgen; AstraZeneca; Boehringer Ingelheim; CSL Behring; Eli Lilly and Company; Esperion Therapeutics; Kowa Pharmaceuticals; Merck; Novo Nordisk; Pfizer; Sanofi Regeneron; Daichii Sankyo; Vaxxinity; Cyclarity; CSL Sequirus; Takeda; Anthera Pharmaceuticals; Cerenis Therapeutics; Infraredx; New Amsterdam Pharma; Novartis; and Resverlogix.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity. 

Michelle L. O’Donoghue, MD, MPH: I’m here at the American Heart Association Scientific Sessions. It’s a very exciting meeting, but one of the interesting topics that we’re going to be talking about is lipoprotein(a) [Lp(a)] . It’s definitely one of the hottest sessions of the meeting.

Joining me to discuss this topic is Dr Steve Nicholls, who is arguably one of the leading experts in the world on lipids. He’s a professor of medicine at Monash University in Australia. Welcome. Thanks, Steve. 

Stephen J. Nicholls, MBBS, PhD: Thanks for having me. 

O’Donoghue: There are two phase 2 studies that we’ll circle back to that are being presented here at the American Heart Association meeting. These are for novel therapeutics that lower Lp(a). Perhaps taking a step back, we know that there’s a large body of evidence to support the concept that Lp(a) plays a causal role in heart disease and atherogenesis, but to date we haven’t had any effective therapies to really lower it.

Thinking about the therapeutics specifically that are on the horizon, perhaps we could start there. Which one is furthest along in development, and how does that look in terms of its ability to lower Lp(a)?

 

Pelacarsen, an ASO

Nicholls: Most of the therapies are injectable. Most of them are nucleic acid–based therapies, and the one that’s most advanced is an agent called pelacarsen. Pelacarsen is an antisense oligonucleotide (ASO), and it has gone all the way through its early phase 2 studies. It has a fully enrolled cardiovascular outcome trial.

We’re all eagerly awaiting the results of that study sometime in the next year or so. That will be the first large-scale clinical trial that will give us some clinical validation to ask the question of whether substantive lowering of Lp(a) will lower cardiovascular risk, with an agent that in early studies looks like it lowers Lp(a) about 80%.

O’Donoghue: Which is tremendous, because again, we really don’t have any effective therapies right now. I guess one of the big questions is, how much do we need to lower Lp(a) for that to translate into meaningful clinical benefit? What’s your sense there? 

Nicholls: Well, we simply don’t know. We’ve tried to look to genetics to try and give us some sort of sense in terms of what that looks like. Lp(a) is a little tricky because the assays and the numbers that get spit out can be tricky in terms of trying to compare apples and apples in different studies. 

We think that it’s probably at least a 50- to 75-mg/dL lowering of Lp(a) using the old units. We think that pelacarsen would hit that, and so our hope is that that would translate to a 15%-20% reduction in major cardiovascular events, but again, we’ve never asked this question before. 

We have data from PCSK9 inhibitor trials showing that lesser reductions in Lp(a) of 25%-30% with both evolocumab and alirocumab contributed to the clinical benefit that we saw in those studies. Those agents were really good at lowering low-density lipoprotein (LDL) cholesterol, but Lp(a) lowering seemed to matter. One would be very hopeful that if a 25%-30% lowering of Lp(a) is useful, then an 80% or greater lowering of Lp(a) should be really useful. 

 

The siRNAs

O’Donoghue: In addition to the ASO pelacarsen that you mentioned, there are several therapeutics in the pipeline, including three small interfering (si) RNAs that are at least in phase 2 and phase 3 testing at this point in time. There’s olpasiran, which in phase 2 testing led to more than a 95% reduction in Lp(a), and then lepodisiran , which has now moved into phase 3  testing, albeit we haven’t seen yet the phase 2  results. 

What is your sense of lepodisiran and its efficacy? 

Nicholls: What’s been really quite striking about the siRNAs is the even more profound degree of lowering of Lp(a) that we’re seeing. We’re seeing 90% and greater lowering of Lp(a) in all of those programs. We’re seeing some differences between the programs in terms of the durability of that effect. 

I think it would be fair to say that with zerlasiran we’re starting to see perhaps that lowering effect starts to taper off a little bit more quickly than the other two. I think that may have some implications in terms of what dosing regimens may look like in the future. 

Even so, we’re talking about therapies that may be dosed 3- to 6-monthly, or even with the potential for being less frequent than that with lepodisiran. Again, I think the phase 2 data will be really important in terms of giving us more information.

O’Donoghue: For the lepodisiran results, I was really quite struck that even though it was small numbers, single dose administered, it really looked like the duration of effect persisted at the higher doses up to about a year. 

Nicholls: It looks pretty promising. We’ve launched the ACCLAIM study, the large cardiovascular outcome trial of lepodisiran, with a 6-monthly regimen. We are hopeful that more information may be able to give us the opportunity for even less frequent administration. 

That has really important implications for patients where adherence is a particular issue. They may just simply want to come into the clinic. You know, once or twice a year, very much like we’re seeing with inclisiran, and that may be a really effective approach for many patients. 

O’Donoghue: You alluded to the zerlasiran results, which were presented here at the American Heart Association meeting, and that even though it led to a robust reduction in Lp(a), it looked like the durability component was maybe a little bit shorter than for some of the other siRNAs that are currently being evaluated.

What’s your sense of that? 

Nicholls: It probably is. The implications clinically, at least in an outcome trial when they ultimately get to that point, probably aren’t that important. They’ll probably just have slightly more frequent administration. That may become a bigger issue when it gets out into the clinic.

The nice thing is that if all of these agents appear to be effective, are well tolerated, and get out to the clinic, then clinicians and patients are going to have a lot of choice. 

O’Donoghue: I think more competition is always good news for the field, ultimately. I think to your point, especially for a drug that might be self-administered, ultimately, whether it’s once a month or once every 3 months, it doesn’t probably make much difference. I think different choices are needed for different patients. 

Perhaps that’s a perfect segue to talk about the oral Lp(a) inhibitor that is also being developed. You presented these results for muvalaplin. 

 

Muvalaplin, an Oral Small Molecule

Nicholls: In terms of frequency of administration, we’re talking about a daily oral therapeutic. For patients who don’t want an injectable and are happy to take a tablet every day, muvalaplin has the potential to be a really good option for them. 

Muvalaplin is an oral small-molecule inhibitor. It essentially prevents apolipoprotein(a) [apo(a)] from binding to apolipoprotein B (apo B). We presented phase 1 data  at the European Society of Cardiology meeting last year, showing probably Lp(a) lowering on the order of about 65%. Here, we’re going to show that that’s a little bit more. It looks like it’s probably at least 70% lowering using a standard Lp(a) assay. Using an assay that looks specifically at intact Lp(a) particles, it’s probably well in excess of 80%.

Those are really good results. The safety and tolerability with muvalaplin look really good. Again, we’ll need to see that agent move forward into a large outcome trial and we’ve yet to hear about that, at least for now. 

O’Donoghue: It’s an interesting challenge that you faced in terms of the assay because, as you say, it really disrupts the apo(a) from binding to the apo B particle, and hence, a traditional assay that just measures apo(a), regardless of whether or not it’s bound to an apo B particle, may be a conservative estimate.

Nicholls: It may, in particular, because we know that apo(a) ultimately then binds to the drug. That assay is measuring what we think is nonfunctional apo(a) in addition to functional apo(a). It’s measuring functional apo(a) that’s still on an actual Lp(a) particle, but if it’s bound to muvalaplin, we think to some degree that’s probably unfair to count that. That’s why trying to develop other assays to try and understand the full effect of the drug is really important in terms of trying to understand how we develop that and move that forward.

O’Donoghue: Is there any evidence yet that the apo(a) particle that is not bound to apo B is in fact nonfunctional as you described it? 

Nicholls: We think that’s likely to be the case, but I think there continues to be research in that space to try and settle that question once and for all. 

O’Donoghue: Again, I think it’s a really exciting time in this field. Right now, we have three ongoing phase 3 trials. We have the pelacarsen trial that is still in follow-up, and fingers crossed, maybe will report out next year. Olpasiran is also in phase 3 testing, completed enrollment, and also is in the follow-up period. We also have lepodisiran, the ACCLAIM trial, as you mentioned. For people who are perhaps watching and looking to enroll their patients, this trial is still ongoing right now in terms of enrollment. 

Nicholls: It is, and what’s nice about the ACCLAIM study is that it includes both primary and secondary prevention patients. For the first time in a big outcome trial, patients with high Lp(a) levels but who have yet to have a clinical event can actually get into a clinical trial.

I’m sure, like you, my clinic is full of patients with high Lp(a) who are really desperate to get into these trials. Many of those primary prevention patients just simply haven’t qualified, so that’s really good news. 

The step beyond that, if we’re talking about even less frequent administration, is gene editing. We’re seeing those studies with CRISPR move forward to try to evaluate whether a single gene-editing approach at Lp(a) will be all that you need, which is even a more amazing concept, but that’s a study that needs more work. 

O’Donoghue: An exciting space though, for sure. As a final thought, you mentioned the patients in your clinic who you have identified as having high Lp(a). What are you doing right now in your practice for managing those patients? I think there are many practitioners out there who struggle with whether they should really measure their patients’ Lp(a), and whether they want to know that information.

Nicholls: Yeah, it’s really hard. The answer is yes, we do want to know it. We know it’s a great risk enhancer. We know that a patient with a high Lp(a) is somebody whom I want to more intensively treat their other risk factors. I’m aiming for a lower LDL. I’m being much tighter with blood pressure control.

I think there’s some argument from observational data at least that aspirin remains a consideration, particularly in patients where you think there’s a particularly high risk associated with that high Lp(a). I think there are things we absolutely can do today, but we can’t do anything if you don’t know the numbers.

It starts with testing, and then we can move on to what we can do today, and then hopefully in the not-too-distant future, we’ll have specific therapies that really enable for us to address Lp(a) quite definitively. 

O’Donoghue: Thanks again for taking the time. This was a very helpful discussion.

 

Michelle O’Donoghue is a cardiologist at Brigham and Women’s Hospital and senior investigator with the TIMI Study Group. A strong believer in evidence-based medicine, she relishes discussions about the published literature. A native Canadian, Michelle loves spending time outdoors with her family but admits with shame that she’s never strapped on hockey skates. Dr O’Donoghue, Senior Investigator, TIMI Study Group; Associate Professor of Medicine, Harvard Medical School; Associate Physician, Brigham and Women’s Hospital, Boston, Massachusetts, disclosed ties to Janssen; Novartis; CVS Minute Clinic; Merck & Co.; GlaxoSmithKline; Eisai Inc.; AstraZeneca Pharmaceuticals LP; Janssen Pharmaceuticals; Medicines Company; and Amgen. The opinions expressed in this article do not necessarily reflect the views and opinions of Brigham and Women’s Hospital. Stephen J. Nicholls, MBBS, PhD, Director, Victorian Heart Institute, Monash University; Director, Victorian Heart Hospital, Monash Health, Melbourne, Australia, has disclosed ties with Akcea Therapeutics; Amgen; AstraZeneca; Boehringer Ingelheim; CSL Behring; Eli Lilly and Company; Esperion Therapeutics; Kowa Pharmaceuticals; Merck; Novo Nordisk; Pfizer; Sanofi Regeneron; Daichii Sankyo; Vaxxinity; Cyclarity; CSL Sequirus; Takeda; Anthera Pharmaceuticals; Cerenis Therapeutics; Infraredx; New Amsterdam Pharma; Novartis; and Resverlogix.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity. 

Michelle L. O’Donoghue, MD, MPH: I’m here at the American Heart Association Scientific Sessions. It’s a very exciting meeting, but one of the interesting topics that we’re going to be talking about is lipoprotein(a) [Lp(a)] . It’s definitely one of the hottest sessions of the meeting.

Joining me to discuss this topic is Dr Steve Nicholls, who is arguably one of the leading experts in the world on lipids. He’s a professor of medicine at Monash University in Australia. Welcome. Thanks, Steve. 

Stephen J. Nicholls, MBBS, PhD: Thanks for having me. 

O’Donoghue: There are two phase 2 studies that we’ll circle back to that are being presented here at the American Heart Association meeting. These are for novel therapeutics that lower Lp(a). Perhaps taking a step back, we know that there’s a large body of evidence to support the concept that Lp(a) plays a causal role in heart disease and atherogenesis, but to date we haven’t had any effective therapies to really lower it.

Thinking about the therapeutics specifically that are on the horizon, perhaps we could start there. Which one is furthest along in development, and how does that look in terms of its ability to lower Lp(a)?

 

Pelacarsen, an ASO

Nicholls: Most of the therapies are injectable. Most of them are nucleic acid–based therapies, and the one that’s most advanced is an agent called pelacarsen. Pelacarsen is an antisense oligonucleotide (ASO), and it has gone all the way through its early phase 2 studies. It has a fully enrolled cardiovascular outcome trial.

We’re all eagerly awaiting the results of that study sometime in the next year or so. That will be the first large-scale clinical trial that will give us some clinical validation to ask the question of whether substantive lowering of Lp(a) will lower cardiovascular risk, with an agent that in early studies looks like it lowers Lp(a) about 80%.

O’Donoghue: Which is tremendous, because again, we really don’t have any effective therapies right now. I guess one of the big questions is, how much do we need to lower Lp(a) for that to translate into meaningful clinical benefit? What’s your sense there? 

Nicholls: Well, we simply don’t know. We’ve tried to look to genetics to try and give us some sort of sense in terms of what that looks like. Lp(a) is a little tricky because the assays and the numbers that get spit out can be tricky in terms of trying to compare apples and apples in different studies. 

We think that it’s probably at least a 50- to 75-mg/dL lowering of Lp(a) using the old units. We think that pelacarsen would hit that, and so our hope is that that would translate to a 15%-20% reduction in major cardiovascular events, but again, we’ve never asked this question before. 

We have data from PCSK9 inhibitor trials showing that lesser reductions in Lp(a) of 25%-30% with both evolocumab and alirocumab contributed to the clinical benefit that we saw in those studies. Those agents were really good at lowering low-density lipoprotein (LDL) cholesterol, but Lp(a) lowering seemed to matter. One would be very hopeful that if a 25%-30% lowering of Lp(a) is useful, then an 80% or greater lowering of Lp(a) should be really useful. 

 

The siRNAs

O’Donoghue: In addition to the ASO pelacarsen that you mentioned, there are several therapeutics in the pipeline, including three small interfering (si) RNAs that are at least in phase 2 and phase 3 testing at this point in time. There’s olpasiran, which in phase 2 testing led to more than a 95% reduction in Lp(a), and then lepodisiran , which has now moved into phase 3  testing, albeit we haven’t seen yet the phase 2  results. 

What is your sense of lepodisiran and its efficacy? 

Nicholls: What’s been really quite striking about the siRNAs is the even more profound degree of lowering of Lp(a) that we’re seeing. We’re seeing 90% and greater lowering of Lp(a) in all of those programs. We’re seeing some differences between the programs in terms of the durability of that effect. 

I think it would be fair to say that with zerlasiran we’re starting to see perhaps that lowering effect starts to taper off a little bit more quickly than the other two. I think that may have some implications in terms of what dosing regimens may look like in the future. 

Even so, we’re talking about therapies that may be dosed 3- to 6-monthly, or even with the potential for being less frequent than that with lepodisiran. Again, I think the phase 2 data will be really important in terms of giving us more information.

O’Donoghue: For the lepodisiran results, I was really quite struck that even though it was small numbers, single dose administered, it really looked like the duration of effect persisted at the higher doses up to about a year. 

Nicholls: It looks pretty promising. We’ve launched the ACCLAIM study, the large cardiovascular outcome trial of lepodisiran, with a 6-monthly regimen. We are hopeful that more information may be able to give us the opportunity for even less frequent administration. 

That has really important implications for patients where adherence is a particular issue. They may just simply want to come into the clinic. You know, once or twice a year, very much like we’re seeing with inclisiran, and that may be a really effective approach for many patients. 

O’Donoghue: You alluded to the zerlasiran results, which were presented here at the American Heart Association meeting, and that even though it led to a robust reduction in Lp(a), it looked like the durability component was maybe a little bit shorter than for some of the other siRNAs that are currently being evaluated.

What’s your sense of that? 

Nicholls: It probably is. The implications clinically, at least in an outcome trial when they ultimately get to that point, probably aren’t that important. They’ll probably just have slightly more frequent administration. That may become a bigger issue when it gets out into the clinic.

The nice thing is that if all of these agents appear to be effective, are well tolerated, and get out to the clinic, then clinicians and patients are going to have a lot of choice. 

O’Donoghue: I think more competition is always good news for the field, ultimately. I think to your point, especially for a drug that might be self-administered, ultimately, whether it’s once a month or once every 3 months, it doesn’t probably make much difference. I think different choices are needed for different patients. 

Perhaps that’s a perfect segue to talk about the oral Lp(a) inhibitor that is also being developed. You presented these results for muvalaplin. 

 

Muvalaplin, an Oral Small Molecule

Nicholls: In terms of frequency of administration, we’re talking about a daily oral therapeutic. For patients who don’t want an injectable and are happy to take a tablet every day, muvalaplin has the potential to be a really good option for them. 

Muvalaplin is an oral small-molecule inhibitor. It essentially prevents apolipoprotein(a) [apo(a)] from binding to apolipoprotein B (apo B). We presented phase 1 data  at the European Society of Cardiology meeting last year, showing probably Lp(a) lowering on the order of about 65%. Here, we’re going to show that that’s a little bit more. It looks like it’s probably at least 70% lowering using a standard Lp(a) assay. Using an assay that looks specifically at intact Lp(a) particles, it’s probably well in excess of 80%.

Those are really good results. The safety and tolerability with muvalaplin look really good. Again, we’ll need to see that agent move forward into a large outcome trial and we’ve yet to hear about that, at least for now. 

O’Donoghue: It’s an interesting challenge that you faced in terms of the assay because, as you say, it really disrupts the apo(a) from binding to the apo B particle, and hence, a traditional assay that just measures apo(a), regardless of whether or not it’s bound to an apo B particle, may be a conservative estimate.

Nicholls: It may, in particular, because we know that apo(a) ultimately then binds to the drug. That assay is measuring what we think is nonfunctional apo(a) in addition to functional apo(a). It’s measuring functional apo(a) that’s still on an actual Lp(a) particle, but if it’s bound to muvalaplin, we think to some degree that’s probably unfair to count that. That’s why trying to develop other assays to try and understand the full effect of the drug is really important in terms of trying to understand how we develop that and move that forward.

O’Donoghue: Is there any evidence yet that the apo(a) particle that is not bound to apo B is in fact nonfunctional as you described it? 

Nicholls: We think that’s likely to be the case, but I think there continues to be research in that space to try and settle that question once and for all. 

O’Donoghue: Again, I think it’s a really exciting time in this field. Right now, we have three ongoing phase 3 trials. We have the pelacarsen trial that is still in follow-up, and fingers crossed, maybe will report out next year. Olpasiran is also in phase 3 testing, completed enrollment, and also is in the follow-up period. We also have lepodisiran, the ACCLAIM trial, as you mentioned. For people who are perhaps watching and looking to enroll their patients, this trial is still ongoing right now in terms of enrollment. 

Nicholls: It is, and what’s nice about the ACCLAIM study is that it includes both primary and secondary prevention patients. For the first time in a big outcome trial, patients with high Lp(a) levels but who have yet to have a clinical event can actually get into a clinical trial.

I’m sure, like you, my clinic is full of patients with high Lp(a) who are really desperate to get into these trials. Many of those primary prevention patients just simply haven’t qualified, so that’s really good news. 

The step beyond that, if we’re talking about even less frequent administration, is gene editing. We’re seeing those studies with CRISPR move forward to try to evaluate whether a single gene-editing approach at Lp(a) will be all that you need, which is even a more amazing concept, but that’s a study that needs more work. 

O’Donoghue: An exciting space though, for sure. As a final thought, you mentioned the patients in your clinic who you have identified as having high Lp(a). What are you doing right now in your practice for managing those patients? I think there are many practitioners out there who struggle with whether they should really measure their patients’ Lp(a), and whether they want to know that information.

Nicholls: Yeah, it’s really hard. The answer is yes, we do want to know it. We know it’s a great risk enhancer. We know that a patient with a high Lp(a) is somebody whom I want to more intensively treat their other risk factors. I’m aiming for a lower LDL. I’m being much tighter with blood pressure control.

I think there’s some argument from observational data at least that aspirin remains a consideration, particularly in patients where you think there’s a particularly high risk associated with that high Lp(a). I think there are things we absolutely can do today, but we can’t do anything if you don’t know the numbers.

It starts with testing, and then we can move on to what we can do today, and then hopefully in the not-too-distant future, we’ll have specific therapies that really enable for us to address Lp(a) quite definitively. 

O’Donoghue: Thanks again for taking the time. This was a very helpful discussion.

 

Michelle O’Donoghue is a cardiologist at Brigham and Women’s Hospital and senior investigator with the TIMI Study Group. A strong believer in evidence-based medicine, she relishes discussions about the published literature. A native Canadian, Michelle loves spending time outdoors with her family but admits with shame that she’s never strapped on hockey skates. Dr O’Donoghue, Senior Investigator, TIMI Study Group; Associate Professor of Medicine, Harvard Medical School; Associate Physician, Brigham and Women’s Hospital, Boston, Massachusetts, disclosed ties to Janssen; Novartis; CVS Minute Clinic; Merck & Co.; GlaxoSmithKline; Eisai Inc.; AstraZeneca Pharmaceuticals LP; Janssen Pharmaceuticals; Medicines Company; and Amgen. The opinions expressed in this article do not necessarily reflect the views and opinions of Brigham and Women’s Hospital. Stephen J. Nicholls, MBBS, PhD, Director, Victorian Heart Institute, Monash University; Director, Victorian Heart Hospital, Monash Health, Melbourne, Australia, has disclosed ties with Akcea Therapeutics; Amgen; AstraZeneca; Boehringer Ingelheim; CSL Behring; Eli Lilly and Company; Esperion Therapeutics; Kowa Pharmaceuticals; Merck; Novo Nordisk; Pfizer; Sanofi Regeneron; Daichii Sankyo; Vaxxinity; Cyclarity; CSL Sequirus; Takeda; Anthera Pharmaceuticals; Cerenis Therapeutics; Infraredx; New Amsterdam Pharma; Novartis; and Resverlogix.

A version of this article appeared on Medscape.com.

An electronic nudge explaining the cardiovascular benefits of the influenza vaccine increased vaccination rates, particularly among people who had previously had a heart attack, showed the NUDGE FLU series of clinical trials.

Influenza has the potential to be a dangerous infection on its own, but it increases the risk for cardiovascular events among people with a history of heart attack, said the study’s lead author, Ankeet Bhatt, MD, a cardiologist at Kaiser Permanente San Francisco Medical Center, San Francisco.

“Yearly influenza vaccines help prevent influenza infection and, in patients with a heart attack, are potentially cardioprotective,” he said during his presentation at the American Heart Association (AHA) Scientific Sessions 2024 in Chicago. The NUDGE FLU results were simultaneously published online in JAMA Cardiology.

In Denmark, where the trials were conducted, about 80% of older adults get flu shots, but only about 40% of younger adults with chronic diseases do, Bhatt reported. In the United States, about 45% of adults and 55% of children received at least one dose of the flu vaccine in the 2023/24 flu season, according to the US Centers for Disease Control and Prevention (CDC).

 

The NUDGE FLU Trials

Bhatt and his colleagues conducted three related clinical trials during the 2022/23 and 2023/24 flu seasons: NUDGE-FLU and NUDGE-FLU-2 targeted older adults, whereas NUDGE-FLU-CHRONIC targeted younger adults with chronic diseases. Nearly 2 million people were involved in the three trials.

Participants were randomized to receive one of a series of different behavioral-science-informed letters, delivered through a government-run electronic communication system, or no reminder.

People who received any of the nudges had higher rates of vaccination; among heart attack survivors, there was a 1.8% improvement and among adults without a history of heart attack, there was a 1.3% improvement. But a nudge that explained the potential cardiovascular benefits of flu shots was even more effective, leading to a 3.9% increase among people with a history of heart attack and a 2% increase among those with no heart attack history.

“A simple sentence resulted in a durable improvement in the vaccination rate,” said Bhatt.

The effect was even greater among those who had not been vaccinated in the previous flu season. Among heart attack survivors, nearly 14% more people got the vaccine compared with just 1.5% more survivors who were previously vaccinated. And it was most effective among younger adults who had experienced a recent heart attack, resulting in a 26% increase.

“The impact was larger in patients with a history of acute myocardial infarction, in those who were vaccine-hesitant, and in younger people” — all groups with the most to gain from vaccination in terms of cardiovascular protection — Bhatt reported.

About 25% of people in the United States are unsure about whether to get a flu shot, said Orly Vardeny, PharmD, professor of medicine at the University of Minnesota Medical School in Minneapolis, who was not involved in the study. The fact that previously unvaccinated people were convinced by the nudges is reassuring. “That’s the group where this intervention is most likely to move the needle,” she said.

Around half of all people hospitalized for flu in the United States have cardiovascular disease, CDC data showed, so “even a small increase in the number of patients who get vaccinated has substantial public health benefits,” Vardeny said.

The NUDGE FLU series showed that nudges like this should be employed as a simple tool to improve vaccination rates, but the system would be much more difficult to implement in the United States, Bhatt said.

Denmark has a national health service and a preexisting government electronic communication system, whereas the US system is privately run and more fractured. It would be possible to make it work, he pointed out, but would take some effort.

A version of this article first appeared on Medscape.com.

An electronic nudge explaining the cardiovascular benefits of the influenza vaccine increased vaccination rates, particularly among people who had previously had a heart attack, showed the NUDGE FLU series of clinical trials.

Influenza has the potential to be a dangerous infection on its own, but it increases the risk for cardiovascular events among people with a history of heart attack, said the study’s lead author, Ankeet Bhatt, MD, a cardiologist at Kaiser Permanente San Francisco Medical Center, San Francisco.

“Yearly influenza vaccines help prevent influenza infection and, in patients with a heart attack, are potentially cardioprotective,” he said during his presentation at the American Heart Association (AHA) Scientific Sessions 2024 in Chicago. The NUDGE FLU results were simultaneously published online in JAMA Cardiology.

In Denmark, where the trials were conducted, about 80% of older adults get flu shots, but only about 40% of younger adults with chronic diseases do, Bhatt reported. In the United States, about 45% of adults and 55% of children received at least one dose of the flu vaccine in the 2023/24 flu season, according to the US Centers for Disease Control and Prevention (CDC).

 

The NUDGE FLU Trials

Bhatt and his colleagues conducted three related clinical trials during the 2022/23 and 2023/24 flu seasons: NUDGE-FLU and NUDGE-FLU-2 targeted older adults, whereas NUDGE-FLU-CHRONIC targeted younger adults with chronic diseases. Nearly 2 million people were involved in the three trials.

Participants were randomized to receive one of a series of different behavioral-science-informed letters, delivered through a government-run electronic communication system, or no reminder.

People who received any of the nudges had higher rates of vaccination; among heart attack survivors, there was a 1.8% improvement and among adults without a history of heart attack, there was a 1.3% improvement. But a nudge that explained the potential cardiovascular benefits of flu shots was even more effective, leading to a 3.9% increase among people with a history of heart attack and a 2% increase among those with no heart attack history.

“A simple sentence resulted in a durable improvement in the vaccination rate,” said Bhatt.

The effect was even greater among those who had not been vaccinated in the previous flu season. Among heart attack survivors, nearly 14% more people got the vaccine compared with just 1.5% more survivors who were previously vaccinated. And it was most effective among younger adults who had experienced a recent heart attack, resulting in a 26% increase.

“The impact was larger in patients with a history of acute myocardial infarction, in those who were vaccine-hesitant, and in younger people” — all groups with the most to gain from vaccination in terms of cardiovascular protection — Bhatt reported.

About 25% of people in the United States are unsure about whether to get a flu shot, said Orly Vardeny, PharmD, professor of medicine at the University of Minnesota Medical School in Minneapolis, who was not involved in the study. The fact that previously unvaccinated people were convinced by the nudges is reassuring. “That’s the group where this intervention is most likely to move the needle,” she said.

Around half of all people hospitalized for flu in the United States have cardiovascular disease, CDC data showed, so “even a small increase in the number of patients who get vaccinated has substantial public health benefits,” Vardeny said.

The NUDGE FLU series showed that nudges like this should be employed as a simple tool to improve vaccination rates, but the system would be much more difficult to implement in the United States, Bhatt said.

Denmark has a national health service and a preexisting government electronic communication system, whereas the US system is privately run and more fractured. It would be possible to make it work, he pointed out, but would take some effort.

A version of this article first appeared on Medscape.com.

An electronic nudge explaining the cardiovascular benefits of the influenza vaccine increased vaccination rates, particularly among people who had previously had a heart attack, showed the NUDGE FLU series of clinical trials.

Influenza has the potential to be a dangerous infection on its own, but it increases the risk for cardiovascular events among people with a history of heart attack, said the study’s lead author, Ankeet Bhatt, MD, a cardiologist at Kaiser Permanente San Francisco Medical Center, San Francisco.

“Yearly influenza vaccines help prevent influenza infection and, in patients with a heart attack, are potentially cardioprotective,” he said during his presentation at the American Heart Association (AHA) Scientific Sessions 2024 in Chicago. The NUDGE FLU results were simultaneously published online in JAMA Cardiology.

In Denmark, where the trials were conducted, about 80% of older adults get flu shots, but only about 40% of younger adults with chronic diseases do, Bhatt reported. In the United States, about 45% of adults and 55% of children received at least one dose of the flu vaccine in the 2023/24 flu season, according to the US Centers for Disease Control and Prevention (CDC).

 

The NUDGE FLU Trials

Bhatt and his colleagues conducted three related clinical trials during the 2022/23 and 2023/24 flu seasons: NUDGE-FLU and NUDGE-FLU-2 targeted older adults, whereas NUDGE-FLU-CHRONIC targeted younger adults with chronic diseases. Nearly 2 million people were involved in the three trials.

Participants were randomized to receive one of a series of different behavioral-science-informed letters, delivered through a government-run electronic communication system, or no reminder.

People who received any of the nudges had higher rates of vaccination; among heart attack survivors, there was a 1.8% improvement and among adults without a history of heart attack, there was a 1.3% improvement. But a nudge that explained the potential cardiovascular benefits of flu shots was even more effective, leading to a 3.9% increase among people with a history of heart attack and a 2% increase among those with no heart attack history.

“A simple sentence resulted in a durable improvement in the vaccination rate,” said Bhatt.

The effect was even greater among those who had not been vaccinated in the previous flu season. Among heart attack survivors, nearly 14% more people got the vaccine compared with just 1.5% more survivors who were previously vaccinated. And it was most effective among younger adults who had experienced a recent heart attack, resulting in a 26% increase.

“The impact was larger in patients with a history of acute myocardial infarction, in those who were vaccine-hesitant, and in younger people” — all groups with the most to gain from vaccination in terms of cardiovascular protection — Bhatt reported.

About 25% of people in the United States are unsure about whether to get a flu shot, said Orly Vardeny, PharmD, professor of medicine at the University of Minnesota Medical School in Minneapolis, who was not involved in the study. The fact that previously unvaccinated people were convinced by the nudges is reassuring. “That’s the group where this intervention is most likely to move the needle,” she said.

Around half of all people hospitalized for flu in the United States have cardiovascular disease, CDC data showed, so “even a small increase in the number of patients who get vaccinated has substantial public health benefits,” Vardeny said.

The NUDGE FLU series showed that nudges like this should be employed as a simple tool to improve vaccination rates, but the system would be much more difficult to implement in the United States, Bhatt said.

Denmark has a national health service and a preexisting government electronic communication system, whereas the US system is privately run and more fractured. It would be possible to make it work, he pointed out, but would take some effort.

A version of this article first appeared on Medscape.com.

Vaccines recommended by the Advisory Committee on Immunization Practices (ACIP) offer important protection against severe illness for pregnant people and their babies.¹ However, vaccination coverage estimates among pregnant people remain suboptimal.^2-5 Additionally, some measures indicate that vaccine hesitancy among pregnant people is increasing; for example, 17.5% of surveyed pregnant women reported being very hesitant about influenza vaccination during pregnancy in 2019-2020, compared with 24.7% in 2022-2023.⁶As fall and winter virus season continues, consider opportunities for you and your staff to help communicate the importance of prenatal vaccination to pregnant patients in your care. Explore updated provider toolkits and prenatal vaccination patient education resources, including fact sheets, social media assets, posters, and short videos on respiratory syncytial virus (RSV), Tdap, COVID-19, influenza, and hepatitis B.

In an interview, CDC’s Haben Debessai, MD, an adjunct instructor in obstetrics and gynecology at Emory School of Medicine, Atlanta, Georgia, contextualizes the data to help healthcare professionals communicate effectively with their pregnant patients. 

 

What can practitioners communicate to patients about why it is important to get vaccinated during their pregnancy?

When communicating with their patients, practitioners can consider opportunities to discuss how vaccines work during pregnancy, emphasizing that prenatal vaccinations are beneficial for both the pregnant person and the fetus. It can be helpful to educate patients on how a pregnant person’s immune system can develop antibodies that will then pass to the fetus during the pregnancy and confer protection during the infant’s early months of life — when they are highly susceptible to illnesses that can be severe, such as RSV-associated lower respiratory tract infections. It can also be useful to discuss pregnancy’s impact on the immune system, which contributes to pregnant people being at higher risk for severe illness from infections like COVID-19 and flu, if contracted. The outcomes of severe illness can be dire for both the pregnant person and their pregnancy, which is why vaccination is the best mitigation option. It can also be beneficial to share with patients that some vaccines, like RSV and Tdap, are specifically for neonatal benefit, which could help patients understand why some vaccines are recommended at a specific gestational age and in each pregnancy or subsequent pregnancies. 

What is known about pregnant populations that experience disparities in vaccination coverage? 

While vaccination coverage among pregnant people is suboptimal, coverage estimates are often lowest among Black pregnant people, some of whom report experiencing mistreatment and discrimination during pregnancy and delivery.⁷ It is important to recognize that there are many intersecting factors that may impact vaccination coverage. Systemic and structural factors may prohibit some patient populations from accessing vaccinations (eg, transportation barriers, difficulty accessing adequate healthcare for those on government assistance, language barriers). To be responsive to the intersectional lived realities of each of these communities, the medical and public health community continually strives to increase trustworthiness, which can lead to increased uptake of vaccinations in these populations. 

What vaccines are available and recommended for pregnant people?

Four vaccines are routinely recommended during pregnancy: Tdap, COVID-19, influenza (seasonal), and RSV (seasonal). CDC recommends getting a Tdap vaccine between the 27th and 36th week of each pregnancy, preferably during the earlier part of this time period. CDC recommends that everyone 6 months or older in the United States, including pregnant people, stay up to date on COVID-19 vaccines. A COVID-19 vaccine can be given during any trimester of pregnancy. CDC recommends an annual flu vaccine during each flu season (fall/winter) for everyone 6 months or older in the United States, including pregnant people. A flu vaccine can be given during any trimester of pregnancy. For individuals who will be between 32 and 36 weeks pregnant during September through January, CDC recommends getting an RSV vaccine. RSV season and timing of vaccination may vary depending on geography. If a pregnant patient does not get the RSV vaccine during their pregnancy, CDC recommends that their baby receive an RSV monoclonal antibody (nirsevimab) to provide additional protection during the infant’s first RSV season, if they are younger than 8 months. At this time, pregnant people who received an RSV vaccine during a previous pregnancy (last year) are not recommended to receive another RSV vaccine during pregnancy. The current recommendation is for babies born during subsequent pregnancies to receive nirsevimab. Some pregnant people may also need other vaccines, such as hepatitis B. 

How can practitioners approach conversations about vaccination during pregnancy amid increasing vaccine hesitancy?

Many pregnant people who do get vaccinated describe their provider’s recommendation as an important motivator toward vaccination.^8-11 Communications research suggests that practitioners can further increase trustworthiness by openly discussing potential side effects of prenatal vaccinations and providing patients with a rationale for why each vaccine is recommended. Practitioners can also utilize opportunities to communicate that the risk for severe illness from whooping cough, COVID-19, flu, and RSV in pregnancy and among neonates in the first few months of life is often higher than the risk for an adverse reaction from receiving ACIP-recommended vaccines. Finally, practitioners can consider sharing tested and refined patient education resources at least one appointment prior to the recommended administration of each vaccine, providing individuals with time to process the information they need to facilitate their vaccine decision-making process.

Some patients may be more comfortable with older, well-known prenatal vaccinations but have skepticism about newer vaccines like COVID-19 and RSV. How can practitioners respond to these concerns?

As pregnant people navigate the challenges of making health decisions that could impact their developing baby, practitioners can build trust through empathetically responding to safety concerns and questions, particularly with respect to newly authorized vaccines. Vaccine confidence may be strengthened by communicating to patients that all recommended vaccinations, including those that have been newly authorized, have been rigorously tested prior to being recommended for pregnant people. Additionally, in my clinical practice, I see that patients are often more comfortable accepting vaccines when the benefit for the baby is clearly communicated. I have been pleasantly surprised that most patients I have counseled on the new maternal RSV vaccine have been receptive, making statements like, “If this will help protect my baby from getting sick, then yes, I will get it.”

As you and your staff care for pregnant patients during fall and winter virus season, remember that a provider recommendation remains one of the strongest known predictors of vaccination uptake.¹² As a trusted source of information about prenatal vaccination, consider further incorporating patient education resources to help communicate how prenatal vaccination helps pregnant people share important protection against severe illnesses with their babies. 

Haben Debessai, MD, is a Gilstrap Fellow at the CDC Foundation. Debessai also serves as an Emory Obstetrics/Gynecology Adjunct Instructor at Grady Health System in Atlanta, Georgia. She disclosed no relevant conflicts of interest.

References

1. ACOG Committee Opinion No. 741: Maternal Immunization. Obstet Gynecol. 2018;131:e214-e217. doi:10.1097/AOG.0000000000002662

2. Centers for Disease Control and Prevention. Flu, Tdap, and COVID-19 vaccination coverage among pregnant women – United States, April 2024. 2024 Sep 23. 3. Centers for Disease Control and Prevention. Respiratory syncytial virus (rsv) vaccination coverage, pregnant persons. 2024 Nov 19. 4. Centers for Disease Control and Prevention. COVID-19 vaccination coverage, pregnant persons. 2024 Nov 19. 5. Centers for Disease Control and Prevention. Influenza vaccination coverage, pregnant persons. 2024 Nov 19.6. Razzaghi H et al. IMMWR Morb Mortal Wkly Rep. 2023;72:1065-1071. Published 2023 Sep 29. doi: 10.15585/mmwr.mm7239a4

7. Mohamoud YA et al. MMWR Morb Mortal Wkly Rep 2023;72:961-967. doi: https://dx.doi.org/10.15585/mmwr.mm7235e1.

8. Kiefer MK et al. Am J Obstet Gynecol MFM. 2022;4:100603. doi: 10.1016/j.ajogmf.2022.100603

9. Spires B et al. Obstet Gynecol Clin North Am. 2023;50:401-419. doi: 10.1016/j.ogc.2023.02.013

10. Wales DP et al. Public Health. 2020;179:38-44. doi: 10.1016/j.puhe.2019.10.001

11. Zimmerman M et al. J Natl Med Assoc. 2023;115:362-376. doi:10.1016/j.jnma.2023.04.003

12. Castillo E et al. Best Pract Res Clin Obstet Gynaecol. 2021;76:83-95. doi:10.1016/j.bpobgyn.2021.03.008

Vaccines recommended by the Advisory Committee on Immunization Practices (ACIP) offer important protection against severe illness for pregnant people and their babies.¹ However, vaccination coverage estimates among pregnant people remain suboptimal.^2-5 Additionally, some measures indicate that vaccine hesitancy among pregnant people is increasing; for example, 17.5% of surveyed pregnant women reported being very hesitant about influenza vaccination during pregnancy in 2019-2020, compared with 24.7% in 2022-2023.⁶As fall and winter virus season continues, consider opportunities for you and your staff to help communicate the importance of prenatal vaccination to pregnant patients in your care. Explore updated provider toolkits and prenatal vaccination patient education resources, including fact sheets, social media assets, posters, and short videos on respiratory syncytial virus (RSV), Tdap, COVID-19, influenza, and hepatitis B.

In an interview, CDC’s Haben Debessai, MD, an adjunct instructor in obstetrics and gynecology at Emory School of Medicine, Atlanta, Georgia, contextualizes the data to help healthcare professionals communicate effectively with their pregnant patients. 

 

What can practitioners communicate to patients about why it is important to get vaccinated during their pregnancy?

When communicating with their patients, practitioners can consider opportunities to discuss how vaccines work during pregnancy, emphasizing that prenatal vaccinations are beneficial for both the pregnant person and the fetus. It can be helpful to educate patients on how a pregnant person’s immune system can develop antibodies that will then pass to the fetus during the pregnancy and confer protection during the infant’s early months of life — when they are highly susceptible to illnesses that can be severe, such as RSV-associated lower respiratory tract infections. It can also be useful to discuss pregnancy’s impact on the immune system, which contributes to pregnant people being at higher risk for severe illness from infections like COVID-19 and flu, if contracted. The outcomes of severe illness can be dire for both the pregnant person and their pregnancy, which is why vaccination is the best mitigation option. It can also be beneficial to share with patients that some vaccines, like RSV and Tdap, are specifically for neonatal benefit, which could help patients understand why some vaccines are recommended at a specific gestational age and in each pregnancy or subsequent pregnancies. 

What is known about pregnant populations that experience disparities in vaccination coverage? 

While vaccination coverage among pregnant people is suboptimal, coverage estimates are often lowest among Black pregnant people, some of whom report experiencing mistreatment and discrimination during pregnancy and delivery.⁷ It is important to recognize that there are many intersecting factors that may impact vaccination coverage. Systemic and structural factors may prohibit some patient populations from accessing vaccinations (eg, transportation barriers, difficulty accessing adequate healthcare for those on government assistance, language barriers). To be responsive to the intersectional lived realities of each of these communities, the medical and public health community continually strives to increase trustworthiness, which can lead to increased uptake of vaccinations in these populations. 

What vaccines are available and recommended for pregnant people?

Four vaccines are routinely recommended during pregnancy: Tdap, COVID-19, influenza (seasonal), and RSV (seasonal). CDC recommends getting a Tdap vaccine between the 27th and 36th week of each pregnancy, preferably during the earlier part of this time period. CDC recommends that everyone 6 months or older in the United States, including pregnant people, stay up to date on COVID-19 vaccines. A COVID-19 vaccine can be given during any trimester of pregnancy. CDC recommends an annual flu vaccine during each flu season (fall/winter) for everyone 6 months or older in the United States, including pregnant people. A flu vaccine can be given during any trimester of pregnancy. For individuals who will be between 32 and 36 weeks pregnant during September through January, CDC recommends getting an RSV vaccine. RSV season and timing of vaccination may vary depending on geography. If a pregnant patient does not get the RSV vaccine during their pregnancy, CDC recommends that their baby receive an RSV monoclonal antibody (nirsevimab) to provide additional protection during the infant’s first RSV season, if they are younger than 8 months. At this time, pregnant people who received an RSV vaccine during a previous pregnancy (last year) are not recommended to receive another RSV vaccine during pregnancy. The current recommendation is for babies born during subsequent pregnancies to receive nirsevimab. Some pregnant people may also need other vaccines, such as hepatitis B. 

How can practitioners approach conversations about vaccination during pregnancy amid increasing vaccine hesitancy?

Many pregnant people who do get vaccinated describe their provider’s recommendation as an important motivator toward vaccination.^8-11 Communications research suggests that practitioners can further increase trustworthiness by openly discussing potential side effects of prenatal vaccinations and providing patients with a rationale for why each vaccine is recommended. Practitioners can also utilize opportunities to communicate that the risk for severe illness from whooping cough, COVID-19, flu, and RSV in pregnancy and among neonates in the first few months of life is often higher than the risk for an adverse reaction from receiving ACIP-recommended vaccines. Finally, practitioners can consider sharing tested and refined patient education resources at least one appointment prior to the recommended administration of each vaccine, providing individuals with time to process the information they need to facilitate their vaccine decision-making process.

Some patients may be more comfortable with older, well-known prenatal vaccinations but have skepticism about newer vaccines like COVID-19 and RSV. How can practitioners respond to these concerns?

As pregnant people navigate the challenges of making health decisions that could impact their developing baby, practitioners can build trust through empathetically responding to safety concerns and questions, particularly with respect to newly authorized vaccines. Vaccine confidence may be strengthened by communicating to patients that all recommended vaccinations, including those that have been newly authorized, have been rigorously tested prior to being recommended for pregnant people. Additionally, in my clinical practice, I see that patients are often more comfortable accepting vaccines when the benefit for the baby is clearly communicated. I have been pleasantly surprised that most patients I have counseled on the new maternal RSV vaccine have been receptive, making statements like, “If this will help protect my baby from getting sick, then yes, I will get it.”

As you and your staff care for pregnant patients during fall and winter virus season, remember that a provider recommendation remains one of the strongest known predictors of vaccination uptake.¹² As a trusted source of information about prenatal vaccination, consider further incorporating patient education resources to help communicate how prenatal vaccination helps pregnant people share important protection against severe illnesses with their babies. 

Haben Debessai, MD, is a Gilstrap Fellow at the CDC Foundation. Debessai also serves as an Emory Obstetrics/Gynecology Adjunct Instructor at Grady Health System in Atlanta, Georgia. She disclosed no relevant conflicts of interest.

References

1. ACOG Committee Opinion No. 741: Maternal Immunization. Obstet Gynecol. 2018;131:e214-e217. doi:10.1097/AOG.0000000000002662

2. Centers for Disease Control and Prevention. Flu, Tdap, and COVID-19 vaccination coverage among pregnant women – United States, April 2024. 2024 Sep 23. 3. Centers for Disease Control and Prevention. Respiratory syncytial virus (rsv) vaccination coverage, pregnant persons. 2024 Nov 19. 4. Centers for Disease Control and Prevention. COVID-19 vaccination coverage, pregnant persons. 2024 Nov 19. 5. Centers for Disease Control and Prevention. Influenza vaccination coverage, pregnant persons. 2024 Nov 19.6. Razzaghi H et al. IMMWR Morb Mortal Wkly Rep. 2023;72:1065-1071. Published 2023 Sep 29. doi: 10.15585/mmwr.mm7239a4

7. Mohamoud YA et al. MMWR Morb Mortal Wkly Rep 2023;72:961-967. doi: https://dx.doi.org/10.15585/mmwr.mm7235e1.

8. Kiefer MK et al. Am J Obstet Gynecol MFM. 2022;4:100603. doi: 10.1016/j.ajogmf.2022.100603

9. Spires B et al. Obstet Gynecol Clin North Am. 2023;50:401-419. doi: 10.1016/j.ogc.2023.02.013

10. Wales DP et al. Public Health. 2020;179:38-44. doi: 10.1016/j.puhe.2019.10.001

11. Zimmerman M et al. J Natl Med Assoc. 2023;115:362-376. doi:10.1016/j.jnma.2023.04.003

12. Castillo E et al. Best Pract Res Clin Obstet Gynaecol. 2021;76:83-95. doi:10.1016/j.bpobgyn.2021.03.008

Vaccines recommended by the Advisory Committee on Immunization Practices (ACIP) offer important protection against severe illness for pregnant people and their babies.¹ However, vaccination coverage estimates among pregnant people remain suboptimal.^2-5 Additionally, some measures indicate that vaccine hesitancy among pregnant people is increasing; for example, 17.5% of surveyed pregnant women reported being very hesitant about influenza vaccination during pregnancy in 2019-2020, compared with 24.7% in 2022-2023.⁶As fall and winter virus season continues, consider opportunities for you and your staff to help communicate the importance of prenatal vaccination to pregnant patients in your care. Explore updated provider toolkits and prenatal vaccination patient education resources, including fact sheets, social media assets, posters, and short videos on respiratory syncytial virus (RSV), Tdap, COVID-19, influenza, and hepatitis B.

In an interview, CDC’s Haben Debessai, MD, an adjunct instructor in obstetrics and gynecology at Emory School of Medicine, Atlanta, Georgia, contextualizes the data to help healthcare professionals communicate effectively with their pregnant patients. 

 

What can practitioners communicate to patients about why it is important to get vaccinated during their pregnancy?

When communicating with their patients, practitioners can consider opportunities to discuss how vaccines work during pregnancy, emphasizing that prenatal vaccinations are beneficial for both the pregnant person and the fetus. It can be helpful to educate patients on how a pregnant person’s immune system can develop antibodies that will then pass to the fetus during the pregnancy and confer protection during the infant’s early months of life — when they are highly susceptible to illnesses that can be severe, such as RSV-associated lower respiratory tract infections. It can also be useful to discuss pregnancy’s impact on the immune system, which contributes to pregnant people being at higher risk for severe illness from infections like COVID-19 and flu, if contracted. The outcomes of severe illness can be dire for both the pregnant person and their pregnancy, which is why vaccination is the best mitigation option. It can also be beneficial to share with patients that some vaccines, like RSV and Tdap, are specifically for neonatal benefit, which could help patients understand why some vaccines are recommended at a specific gestational age and in each pregnancy or subsequent pregnancies. 

What is known about pregnant populations that experience disparities in vaccination coverage? 

While vaccination coverage among pregnant people is suboptimal, coverage estimates are often lowest among Black pregnant people, some of whom report experiencing mistreatment and discrimination during pregnancy and delivery.⁷ It is important to recognize that there are many intersecting factors that may impact vaccination coverage. Systemic and structural factors may prohibit some patient populations from accessing vaccinations (eg, transportation barriers, difficulty accessing adequate healthcare for those on government assistance, language barriers). To be responsive to the intersectional lived realities of each of these communities, the medical and public health community continually strives to increase trustworthiness, which can lead to increased uptake of vaccinations in these populations. 

What vaccines are available and recommended for pregnant people?

Four vaccines are routinely recommended during pregnancy: Tdap, COVID-19, influenza (seasonal), and RSV (seasonal). CDC recommends getting a Tdap vaccine between the 27th and 36th week of each pregnancy, preferably during the earlier part of this time period. CDC recommends that everyone 6 months or older in the United States, including pregnant people, stay up to date on COVID-19 vaccines. A COVID-19 vaccine can be given during any trimester of pregnancy. CDC recommends an annual flu vaccine during each flu season (fall/winter) for everyone 6 months or older in the United States, including pregnant people. A flu vaccine can be given during any trimester of pregnancy. For individuals who will be between 32 and 36 weeks pregnant during September through January, CDC recommends getting an RSV vaccine. RSV season and timing of vaccination may vary depending on geography. If a pregnant patient does not get the RSV vaccine during their pregnancy, CDC recommends that their baby receive an RSV monoclonal antibody (nirsevimab) to provide additional protection during the infant’s first RSV season, if they are younger than 8 months. At this time, pregnant people who received an RSV vaccine during a previous pregnancy (last year) are not recommended to receive another RSV vaccine during pregnancy. The current recommendation is for babies born during subsequent pregnancies to receive nirsevimab. Some pregnant people may also need other vaccines, such as hepatitis B. 

How can practitioners approach conversations about vaccination during pregnancy amid increasing vaccine hesitancy?

Many pregnant people who do get vaccinated describe their provider’s recommendation as an important motivator toward vaccination.^8-11 Communications research suggests that practitioners can further increase trustworthiness by openly discussing potential side effects of prenatal vaccinations and providing patients with a rationale for why each vaccine is recommended. Practitioners can also utilize opportunities to communicate that the risk for severe illness from whooping cough, COVID-19, flu, and RSV in pregnancy and among neonates in the first few months of life is often higher than the risk for an adverse reaction from receiving ACIP-recommended vaccines. Finally, practitioners can consider sharing tested and refined patient education resources at least one appointment prior to the recommended administration of each vaccine, providing individuals with time to process the information they need to facilitate their vaccine decision-making process.

Some patients may be more comfortable with older, well-known prenatal vaccinations but have skepticism about newer vaccines like COVID-19 and RSV. How can practitioners respond to these concerns?

As pregnant people navigate the challenges of making health decisions that could impact their developing baby, practitioners can build trust through empathetically responding to safety concerns and questions, particularly with respect to newly authorized vaccines. Vaccine confidence may be strengthened by communicating to patients that all recommended vaccinations, including those that have been newly authorized, have been rigorously tested prior to being recommended for pregnant people. Additionally, in my clinical practice, I see that patients are often more comfortable accepting vaccines when the benefit for the baby is clearly communicated. I have been pleasantly surprised that most patients I have counseled on the new maternal RSV vaccine have been receptive, making statements like, “If this will help protect my baby from getting sick, then yes, I will get it.”

As you and your staff care for pregnant patients during fall and winter virus season, remember that a provider recommendation remains one of the strongest known predictors of vaccination uptake.¹² As a trusted source of information about prenatal vaccination, consider further incorporating patient education resources to help communicate how prenatal vaccination helps pregnant people share important protection against severe illnesses with their babies. 

Haben Debessai, MD, is a Gilstrap Fellow at the CDC Foundation. Debessai also serves as an Emory Obstetrics/Gynecology Adjunct Instructor at Grady Health System in Atlanta, Georgia. She disclosed no relevant conflicts of interest.

References

1. ACOG Committee Opinion No. 741: Maternal Immunization. Obstet Gynecol. 2018;131:e214-e217. doi:10.1097/AOG.0000000000002662

2. Centers for Disease Control and Prevention. Flu, Tdap, and COVID-19 vaccination coverage among pregnant women – United States, April 2024. 2024 Sep 23. 3. Centers for Disease Control and Prevention. Respiratory syncytial virus (rsv) vaccination coverage, pregnant persons. 2024 Nov 19. 4. Centers for Disease Control and Prevention. COVID-19 vaccination coverage, pregnant persons. 2024 Nov 19. 5. Centers for Disease Control and Prevention. Influenza vaccination coverage, pregnant persons. 2024 Nov 19.6. Razzaghi H et al. IMMWR Morb Mortal Wkly Rep. 2023;72:1065-1071. Published 2023 Sep 29. doi: 10.15585/mmwr.mm7239a4

7. Mohamoud YA et al. MMWR Morb Mortal Wkly Rep 2023;72:961-967. doi: https://dx.doi.org/10.15585/mmwr.mm7235e1.

8. Kiefer MK et al. Am J Obstet Gynecol MFM. 2022;4:100603. doi: 10.1016/j.ajogmf.2022.100603

9. Spires B et al. Obstet Gynecol Clin North Am. 2023;50:401-419. doi: 10.1016/j.ogc.2023.02.013

10. Wales DP et al. Public Health. 2020;179:38-44. doi: 10.1016/j.puhe.2019.10.001

11. Zimmerman M et al. J Natl Med Assoc. 2023;115:362-376. doi:10.1016/j.jnma.2023.04.003

12. Castillo E et al. Best Pract Res Clin Obstet Gynaecol. 2021;76:83-95. doi:10.1016/j.bpobgyn.2021.03.008

This transcript has been edited for clarity. 

Matthew F. Watto, MD: I’m Dr Matthew Frank Watto, here with my great friend and America’s primary care physician, Dr Paul Nelson Williams. 

We had a great discussion with Kidney Boy, Dr Joel Topf, everyone’s favorite nephrologist, and he taught us how to manage blood pressure in chronic kidney disease (CKD).

When should I start freaking out about a patient’s kidney function? 

Paul N. Williams, MD: Dr Topf focuses more on albuminuria than we are used to doing. It’s probably one of the most important prognostic indicators of how a patient is going to do from a renal standpoint.

Historically, I’ve tended to focus on the estimated glomerular filtration rate (eGFR), and the lower that number gets, the more I sweat, but albuminuria is probably equally, if not more, important as a way of prognosticating whether a patient is going to progress to dialysis or transplant. He directed us towards this nifty little calculator, kidneyfailurerisk.com, where you plug in the patient’s age, eGFR, and degree of albuminuria, and it spits out their risk of progressing to hemodialysis or renal transplantation over the next 5 years. It’s a nice way to concretely explain to patients their risk for progression.

Instead of telling the patient, “You are high risk,” Dr Topf will say, “Your risk is 6% of needing dialysis in the next 5 years.” You can even use these thresholds to gauge when to refer a patient. If someone has a 5-year risk between 3% and 5% or higher, that patient should probably be seeing a nephrologist.

If their 2-year risk is greater than 20%, that patient probably should be evaluated for transplantation. This gives us have more concrete numbers to work with rather than just saying, “Your kidneys aren’t working as well as we would like and you should see a kidney doctor.” Patients have a better sense of how serious things might be. 

Watto: It’s just easier for them to understand. Dr Topf made the point that we used to have a heat map based on the stage of CKD that would tell you how high a patient’s risk was compared with other people. But patients don’t really understand relative risk, so Dr Topf tells them their absolute risk for ending up on dialysis over the next 2-5 years. 

Patients come in and they are worried because they looked at their lab results and see that their creatinine level is red, or their eGFR is low. They think, It says I have stage 3a CKD. 

We should probably have the stages of CKD start at stage 3, which should be called stage 1 so it doesn’t sound as bad. Patients think they are halfway to dialysis; they are already at stage 3 and didn’t even know their kidneys were a problem. 

Dr Topf said that cystatin C (something I only recently started ordering) can be obtained, and sometimes you can recategorize the patient, especially those with an eGFR between 45 and 60. The cystatin C can predict their renal function better than the creatinine-based equations. If you are using the creatinine equation, he recommends using the 2021 equations.

Another nice thing about cystatin C is that it isn’t tripped up in younger patients with a lot of muscle mass. You just have to watch out for inflammation, which can throw the test off. For example, when a patient is in the intensive care unit, it’s probably not that helpful, but for your outpatients, cystatin C works well. 

Williams: I’ve been using it a fair amount in my patients with more muscle mass. And some patients have been taking creatine as a supplement, and that can alter the numbers as well. This is a nice way to get them out of CKD stage 2 or 3 and back where they belong, with normal healthy functioning kidneys.

Watto: Now, Paul, if we find a patient with more advanced CKD — let’s say stage 4, whether by cystatin C or serum creatinine, and their eGFR is less than 30 — should we start peeling off the angiotensin-converting enzyme ACE inhibitor or the angiotensin receptor blocker (ARB)? Those drugs can raise potassium. What should we do here? 

Williams: That’s the temptation, Matt, and I feel like that was the old orthodoxy, back in residency. It didn’t take much for us to start taking off ACE inhibitors or ARBs once the kidney function started to drop, but it turns out you may be doing more harm than good.

Some data have shown that if you peel off those medications, you actually increase mortality and cardiovascular risk. So, in general, if you can keep them going, the patient will be better off. Hang onto the ACE inhibitors or ARBs as long as you are able to, because they confer a fair amount of benefit.

Watto: As long as the potassium isn’t in red on your lab’s range. It might go up to 5.2 or 5.4, but as long as it’s stable, that should be OK. You probably wouldn’t initiate an ACE inhibitor or ARB or spironolactone with a potassium level above 5, but if it’s below 5 when you start and it goes up slightly after you start the drug, that could be acceptable. 

Another thing we talked about was when a patient progresses to CKD and ends up on dialysis, how helpful are those intradialysis blood pressures in predicting cardiovascular outcomes? 

Williams: For someone who’s performing the dialysis, probably really helpful. In the outpatient setting to predict cardiovascular risk, probably less so. Dr Topf makes the point that the readings are done either shortly after or right when the patient is about to have a large-bore catheter inserted into their arm. And then they have liters of fluid drained out of them. So those numbers are going to have huge amounts of variability. You would not base the patient’s blood pressure treatment solely on those numbers. But regardless of what the numbers are, or even regardless of your office numbers, hopefully you’re working with a nephrologist to make sure that you’re actually in concert and not fighting each other with the blood pressure medications.

Watto: Dr Topf said that a lot of the hypertension in dialysis is because of too much volume. If you can get the volume down, you might be able to peel off blood pressure medications instead of adding more. But some patients have issues with cramping; it’s uncomfortable and not everyone tolerates it. 

I was really surprised to learn that beta blockers, specifically atenolol, have some evidence of improving cardiovascular outcomes in patients on dialysis. Dr Topf speculated that this was because they are largely dying of cardiovascular disease, so maybe that’s why, but that’s one of the places, the only places I can think of aside from thyroid disease, where atenolol really shines. 

If you want to hear this fantastic episode and all the great pearls, then click on this link. 

Matthew F. Watto, MD, Clinical Assistant Professor, Department of Medicine, Perelman School of Medicine at University of Pennsylvania; Internist, Department of Medicine, Hospital Medicine Section, Pennsylvania Hospital, Philadelphia, Pennsylvania, disclosed no relevant financial relationships. Paul N. Williams, MD, has disclosed ties with The Curbsiders.

This transcript has been edited for clarity. 

Matthew F. Watto, MD: I’m Dr Matthew Frank Watto, here with my great friend and America’s primary care physician, Dr Paul Nelson Williams. 

We had a great discussion with Kidney Boy, Dr Joel Topf, everyone’s favorite nephrologist, and he taught us how to manage blood pressure in chronic kidney disease (CKD).

When should I start freaking out about a patient’s kidney function? 

Paul N. Williams, MD: Dr Topf focuses more on albuminuria than we are used to doing. It’s probably one of the most important prognostic indicators of how a patient is going to do from a renal standpoint.

Historically, I’ve tended to focus on the estimated glomerular filtration rate (eGFR), and the lower that number gets, the more I sweat, but albuminuria is probably equally, if not more, important as a way of prognosticating whether a patient is going to progress to dialysis or transplant. He directed us towards this nifty little calculator, kidneyfailurerisk.com, where you plug in the patient’s age, eGFR, and degree of albuminuria, and it spits out their risk of progressing to hemodialysis or renal transplantation over the next 5 years. It’s a nice way to concretely explain to patients their risk for progression.

Instead of telling the patient, “You are high risk,” Dr Topf will say, “Your risk is 6% of needing dialysis in the next 5 years.” You can even use these thresholds to gauge when to refer a patient. If someone has a 5-year risk between 3% and 5% or higher, that patient should probably be seeing a nephrologist.

If their 2-year risk is greater than 20%, that patient probably should be evaluated for transplantation. This gives us have more concrete numbers to work with rather than just saying, “Your kidneys aren’t working as well as we would like and you should see a kidney doctor.” Patients have a better sense of how serious things might be. 

Watto: It’s just easier for them to understand. Dr Topf made the point that we used to have a heat map based on the stage of CKD that would tell you how high a patient’s risk was compared with other people. But patients don’t really understand relative risk, so Dr Topf tells them their absolute risk for ending up on dialysis over the next 2-5 years. 

Patients come in and they are worried because they looked at their lab results and see that their creatinine level is red, or their eGFR is low. They think, It says I have stage 3a CKD. 

We should probably have the stages of CKD start at stage 3, which should be called stage 1 so it doesn’t sound as bad. Patients think they are halfway to dialysis; they are already at stage 3 and didn’t even know their kidneys were a problem. 

Dr Topf said that cystatin C (something I only recently started ordering) can be obtained, and sometimes you can recategorize the patient, especially those with an eGFR between 45 and 60. The cystatin C can predict their renal function better than the creatinine-based equations. If you are using the creatinine equation, he recommends using the 2021 equations.

Another nice thing about cystatin C is that it isn’t tripped up in younger patients with a lot of muscle mass. You just have to watch out for inflammation, which can throw the test off. For example, when a patient is in the intensive care unit, it’s probably not that helpful, but for your outpatients, cystatin C works well. 

Williams: I’ve been using it a fair amount in my patients with more muscle mass. And some patients have been taking creatine as a supplement, and that can alter the numbers as well. This is a nice way to get them out of CKD stage 2 or 3 and back where they belong, with normal healthy functioning kidneys.

Watto: Now, Paul, if we find a patient with more advanced CKD — let’s say stage 4, whether by cystatin C or serum creatinine, and their eGFR is less than 30 — should we start peeling off the angiotensin-converting enzyme ACE inhibitor or the angiotensin receptor blocker (ARB)? Those drugs can raise potassium. What should we do here? 

Williams: That’s the temptation, Matt, and I feel like that was the old orthodoxy, back in residency. It didn’t take much for us to start taking off ACE inhibitors or ARBs once the kidney function started to drop, but it turns out you may be doing more harm than good.

Some data have shown that if you peel off those medications, you actually increase mortality and cardiovascular risk. So, in general, if you can keep them going, the patient will be better off. Hang onto the ACE inhibitors or ARBs as long as you are able to, because they confer a fair amount of benefit.

Watto: As long as the potassium isn’t in red on your lab’s range. It might go up to 5.2 or 5.4, but as long as it’s stable, that should be OK. You probably wouldn’t initiate an ACE inhibitor or ARB or spironolactone with a potassium level above 5, but if it’s below 5 when you start and it goes up slightly after you start the drug, that could be acceptable. 

Another thing we talked about was when a patient progresses to CKD and ends up on dialysis, how helpful are those intradialysis blood pressures in predicting cardiovascular outcomes? 

Williams: For someone who’s performing the dialysis, probably really helpful. In the outpatient setting to predict cardiovascular risk, probably less so. Dr Topf makes the point that the readings are done either shortly after or right when the patient is about to have a large-bore catheter inserted into their arm. And then they have liters of fluid drained out of them. So those numbers are going to have huge amounts of variability. You would not base the patient’s blood pressure treatment solely on those numbers. But regardless of what the numbers are, or even regardless of your office numbers, hopefully you’re working with a nephrologist to make sure that you’re actually in concert and not fighting each other with the blood pressure medications.

Watto: Dr Topf said that a lot of the hypertension in dialysis is because of too much volume. If you can get the volume down, you might be able to peel off blood pressure medications instead of adding more. But some patients have issues with cramping; it’s uncomfortable and not everyone tolerates it. 

I was really surprised to learn that beta blockers, specifically atenolol, have some evidence of improving cardiovascular outcomes in patients on dialysis. Dr Topf speculated that this was because they are largely dying of cardiovascular disease, so maybe that’s why, but that’s one of the places, the only places I can think of aside from thyroid disease, where atenolol really shines. 

If you want to hear this fantastic episode and all the great pearls, then click on this link. 

Matthew F. Watto, MD, Clinical Assistant Professor, Department of Medicine, Perelman School of Medicine at University of Pennsylvania; Internist, Department of Medicine, Hospital Medicine Section, Pennsylvania Hospital, Philadelphia, Pennsylvania, disclosed no relevant financial relationships. Paul N. Williams, MD, has disclosed ties with The Curbsiders.

This transcript has been edited for clarity. 

Matthew F. Watto, MD: I’m Dr Matthew Frank Watto, here with my great friend and America’s primary care physician, Dr Paul Nelson Williams. 

We had a great discussion with Kidney Boy, Dr Joel Topf, everyone’s favorite nephrologist, and he taught us how to manage blood pressure in chronic kidney disease (CKD).

When should I start freaking out about a patient’s kidney function? 

Paul N. Williams, MD: Dr Topf focuses more on albuminuria than we are used to doing. It’s probably one of the most important prognostic indicators of how a patient is going to do from a renal standpoint.

Historically, I’ve tended to focus on the estimated glomerular filtration rate (eGFR), and the lower that number gets, the more I sweat, but albuminuria is probably equally, if not more, important as a way of prognosticating whether a patient is going to progress to dialysis or transplant. He directed us towards this nifty little calculator, kidneyfailurerisk.com, where you plug in the patient’s age, eGFR, and degree of albuminuria, and it spits out their risk of progressing to hemodialysis or renal transplantation over the next 5 years. It’s a nice way to concretely explain to patients their risk for progression.

Instead of telling the patient, “You are high risk,” Dr Topf will say, “Your risk is 6% of needing dialysis in the next 5 years.” You can even use these thresholds to gauge when to refer a patient. If someone has a 5-year risk between 3% and 5% or higher, that patient should probably be seeing a nephrologist.

If their 2-year risk is greater than 20%, that patient probably should be evaluated for transplantation. This gives us have more concrete numbers to work with rather than just saying, “Your kidneys aren’t working as well as we would like and you should see a kidney doctor.” Patients have a better sense of how serious things might be. 

Watto: It’s just easier for them to understand. Dr Topf made the point that we used to have a heat map based on the stage of CKD that would tell you how high a patient’s risk was compared with other people. But patients don’t really understand relative risk, so Dr Topf tells them their absolute risk for ending up on dialysis over the next 2-5 years. 

Patients come in and they are worried because they looked at their lab results and see that their creatinine level is red, or their eGFR is low. They think, It says I have stage 3a CKD. 

We should probably have the stages of CKD start at stage 3, which should be called stage 1 so it doesn’t sound as bad. Patients think they are halfway to dialysis; they are already at stage 3 and didn’t even know their kidneys were a problem. 

Dr Topf said that cystatin C (something I only recently started ordering) can be obtained, and sometimes you can recategorize the patient, especially those with an eGFR between 45 and 60. The cystatin C can predict their renal function better than the creatinine-based equations. If you are using the creatinine equation, he recommends using the 2021 equations.

Another nice thing about cystatin C is that it isn’t tripped up in younger patients with a lot of muscle mass. You just have to watch out for inflammation, which can throw the test off. For example, when a patient is in the intensive care unit, it’s probably not that helpful, but for your outpatients, cystatin C works well. 

Williams: I’ve been using it a fair amount in my patients with more muscle mass. And some patients have been taking creatine as a supplement, and that can alter the numbers as well. This is a nice way to get them out of CKD stage 2 or 3 and back where they belong, with normal healthy functioning kidneys.

Watto: Now, Paul, if we find a patient with more advanced CKD — let’s say stage 4, whether by cystatin C or serum creatinine, and their eGFR is less than 30 — should we start peeling off the angiotensin-converting enzyme ACE inhibitor or the angiotensin receptor blocker (ARB)? Those drugs can raise potassium. What should we do here? 

Williams: That’s the temptation, Matt, and I feel like that was the old orthodoxy, back in residency. It didn’t take much for us to start taking off ACE inhibitors or ARBs once the kidney function started to drop, but it turns out you may be doing more harm than good.

Some data have shown that if you peel off those medications, you actually increase mortality and cardiovascular risk. So, in general, if you can keep them going, the patient will be better off. Hang onto the ACE inhibitors or ARBs as long as you are able to, because they confer a fair amount of benefit.

Watto: As long as the potassium isn’t in red on your lab’s range. It might go up to 5.2 or 5.4, but as long as it’s stable, that should be OK. You probably wouldn’t initiate an ACE inhibitor or ARB or spironolactone with a potassium level above 5, but if it’s below 5 when you start and it goes up slightly after you start the drug, that could be acceptable. 

Another thing we talked about was when a patient progresses to CKD and ends up on dialysis, how helpful are those intradialysis blood pressures in predicting cardiovascular outcomes? 

Williams: For someone who’s performing the dialysis, probably really helpful. In the outpatient setting to predict cardiovascular risk, probably less so. Dr Topf makes the point that the readings are done either shortly after or right when the patient is about to have a large-bore catheter inserted into their arm. And then they have liters of fluid drained out of them. So those numbers are going to have huge amounts of variability. You would not base the patient’s blood pressure treatment solely on those numbers. But regardless of what the numbers are, or even regardless of your office numbers, hopefully you’re working with a nephrologist to make sure that you’re actually in concert and not fighting each other with the blood pressure medications.

Watto: Dr Topf said that a lot of the hypertension in dialysis is because of too much volume. If you can get the volume down, you might be able to peel off blood pressure medications instead of adding more. But some patients have issues with cramping; it’s uncomfortable and not everyone tolerates it. 

I was really surprised to learn that beta blockers, specifically atenolol, have some evidence of improving cardiovascular outcomes in patients on dialysis. Dr Topf speculated that this was because they are largely dying of cardiovascular disease, so maybe that’s why, but that’s one of the places, the only places I can think of aside from thyroid disease, where atenolol really shines. 

If you want to hear this fantastic episode and all the great pearls, then click on this link. 

Matthew F. Watto, MD, Clinical Assistant Professor, Department of Medicine, Perelman School of Medicine at University of Pennsylvania; Internist, Department of Medicine, Hospital Medicine Section, Pennsylvania Hospital, Philadelphia, Pennsylvania, disclosed no relevant financial relationships. Paul N. Williams, MD, has disclosed ties with The Curbsiders.

TOPLINE:

InterRhythmic care (IRC), a novel digital intervention, was linked to greater improvements in depressive symptoms, anxiety, interpersonal relationships, and social functioning in patients with major depressive disorder (MDD), compared with internet general psychoeducation in new research.

METHODOLOGY:

• The randomized, single-blind trial included 120 outpatients from the Shanghai Mental Health Center between March and November 2021 with MDD (mean age, 28.2 years; 99% Han Chinese; 83% women) who were randomly assigned to receive either IRC or internet general psychoeducation (control group).
• IRC included computer-based psychoeducation on stabilizing social rhythm regularity and resolution of interpersonal problems plus brief online interactions with clinicians. Patients received 10 minutes of IRC daily, Monday through Friday, for 8 weeks.
• The researchers assessed participants’ depressive symptoms, anxiety symptoms, interpersonal relationships, social function, and biological rhythms using the 17-item Hamilton Depression Rating Scale, Hamilton Anxiety Scale, Interpersonal Comprehensive Diagnostic Scale, Sheehan Disability Scale, and Morning and Evening Questionnaire at baseline and at 8 weeks.

TAKEAWAY:

• The participants who received IRC had significantly lower Hamilton Depression Rating total scores than those who received internet general psychoeducation (P < .001).
• The IRC group demonstrated improved anxiety symptoms, as evidenced by lower Hamilton Anxiety Scale total scores, than those observed for the control group (P < .001).
• The IRC group also showed improved outcomes in interpersonal relationships, as indicated by lower Interpersonal Comprehensive Diagnostic Scale total scores (P < .001).
• Social functioning improved significantly in the IRC group, as measured by the Sheehan Disability Scale subscores for work/school (P = .03), social life (P < .001), and family life (P = .001).

IN PRACTICE:

“This study demonstrated that IRC can improve clinical symptoms such as depressive symptoms, anxiety symptoms, interpersonal problems, and social function in patients with MDD. Our study suggested that the IRC can be used in clinical practice,” the investigators wrote.

SOURCE:

The study was led by Chuchen Xu, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine in China. It was published online on November 20, 2024, in The Journal of Psychiatric Research.

LIMITATIONS:

The 8-week follow-up period was considered too short to comprehensively evaluate the intervention’s long-term impact. Additionally, the researchers had to check and supervise assignment completion, which increased research costs and may, therefore, potentially limit broader implementation.

DISCLOSURES:

The investigators reported no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

InterRhythmic care (IRC), a novel digital intervention, was linked to greater improvements in depressive symptoms, anxiety, interpersonal relationships, and social functioning in patients with major depressive disorder (MDD), compared with internet general psychoeducation in new research.

METHODOLOGY:

• The randomized, single-blind trial included 120 outpatients from the Shanghai Mental Health Center between March and November 2021 with MDD (mean age, 28.2 years; 99% Han Chinese; 83% women) who were randomly assigned to receive either IRC or internet general psychoeducation (control group).
• IRC included computer-based psychoeducation on stabilizing social rhythm regularity and resolution of interpersonal problems plus brief online interactions with clinicians. Patients received 10 minutes of IRC daily, Monday through Friday, for 8 weeks.
• The researchers assessed participants’ depressive symptoms, anxiety symptoms, interpersonal relationships, social function, and biological rhythms using the 17-item Hamilton Depression Rating Scale, Hamilton Anxiety Scale, Interpersonal Comprehensive Diagnostic Scale, Sheehan Disability Scale, and Morning and Evening Questionnaire at baseline and at 8 weeks.

TAKEAWAY:

• The participants who received IRC had significantly lower Hamilton Depression Rating total scores than those who received internet general psychoeducation (P < .001).
• The IRC group demonstrated improved anxiety symptoms, as evidenced by lower Hamilton Anxiety Scale total scores, than those observed for the control group (P < .001).
• The IRC group also showed improved outcomes in interpersonal relationships, as indicated by lower Interpersonal Comprehensive Diagnostic Scale total scores (P < .001).
• Social functioning improved significantly in the IRC group, as measured by the Sheehan Disability Scale subscores for work/school (P = .03), social life (P < .001), and family life (P = .001).

IN PRACTICE:

“This study demonstrated that IRC can improve clinical symptoms such as depressive symptoms, anxiety symptoms, interpersonal problems, and social function in patients with MDD. Our study suggested that the IRC can be used in clinical practice,” the investigators wrote.

SOURCE:

The study was led by Chuchen Xu, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine in China. It was published online on November 20, 2024, in The Journal of Psychiatric Research.

LIMITATIONS:

The 8-week follow-up period was considered too short to comprehensively evaluate the intervention’s long-term impact. Additionally, the researchers had to check and supervise assignment completion, which increased research costs and may, therefore, potentially limit broader implementation.

DISCLOSURES:

The investigators reported no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

InterRhythmic care (IRC), a novel digital intervention, was linked to greater improvements in depressive symptoms, anxiety, interpersonal relationships, and social functioning in patients with major depressive disorder (MDD), compared with internet general psychoeducation in new research.

METHODOLOGY:

• The randomized, single-blind trial included 120 outpatients from the Shanghai Mental Health Center between March and November 2021 with MDD (mean age, 28.2 years; 99% Han Chinese; 83% women) who were randomly assigned to receive either IRC or internet general psychoeducation (control group).
• IRC included computer-based psychoeducation on stabilizing social rhythm regularity and resolution of interpersonal problems plus brief online interactions with clinicians. Patients received 10 minutes of IRC daily, Monday through Friday, for 8 weeks.
• The researchers assessed participants’ depressive symptoms, anxiety symptoms, interpersonal relationships, social function, and biological rhythms using the 17-item Hamilton Depression Rating Scale, Hamilton Anxiety Scale, Interpersonal Comprehensive Diagnostic Scale, Sheehan Disability Scale, and Morning and Evening Questionnaire at baseline and at 8 weeks.

TAKEAWAY:

• The participants who received IRC had significantly lower Hamilton Depression Rating total scores than those who received internet general psychoeducation (P < .001).
• The IRC group demonstrated improved anxiety symptoms, as evidenced by lower Hamilton Anxiety Scale total scores, than those observed for the control group (P < .001).
• The IRC group also showed improved outcomes in interpersonal relationships, as indicated by lower Interpersonal Comprehensive Diagnostic Scale total scores (P < .001).
• Social functioning improved significantly in the IRC group, as measured by the Sheehan Disability Scale subscores for work/school (P = .03), social life (P < .001), and family life (P = .001).

IN PRACTICE:

“This study demonstrated that IRC can improve clinical symptoms such as depressive symptoms, anxiety symptoms, interpersonal problems, and social function in patients with MDD. Our study suggested that the IRC can be used in clinical practice,” the investigators wrote.

SOURCE:

The study was led by Chuchen Xu, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine in China. It was published online on November 20, 2024, in The Journal of Psychiatric Research.

LIMITATIONS:

The 8-week follow-up period was considered too short to comprehensively evaluate the intervention’s long-term impact. Additionally, the researchers had to check and supervise assignment completion, which increased research costs and may, therefore, potentially limit broader implementation.

DISCLOSURES:

The investigators reported no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

SAN DIEGO — In patients with metabolic dysfunction–associated steatotic liver disease (MASLD), hypertension, and cirrhosis, certain antihypertensive medications may lead to increased risks for hepatocellular carcinoma (HCC), according to new research.

In particular, the use of calcium channel blockers (CCBs), angiotensin-converting enzyme (ACE) inhibitors, and angiotensin receptor blockers (ARBs) was associated with a higher risk of developing HCC, compared with not using these medications.

About half of patients with MASLD have hypertension, and the use of antihypertensives in these patients is beneficial to reduce the risk for cardiovascular disease and complications related to MASLD, said lead author Ahmed Elhariri, MD, a research fellow at the University of Texas MD Anderson Cancer Center, Houston, who conducted the study as a research assistant in gastroenterology and hepatology at the Baylor College of Medicine, also in Houston.

However, previous studies have suggested a possible link between these medications and cancer development, “especially CCBs and breast and lung cancer,” said Elhariri, who presented the findings at The Liver Meeting 2024: American Association for the Study of Liver Diseases (AASLD).

 

Analyzing Potential Risks

In a case-control study, Elhariri and colleagues analyzed antihypertensive medication use among patients with MASLD-induced HCC, as defined by histology or radiology based on the Liver Imaging Reporting & Data System, and control patients with MASLD but without HCC.

Between 2020 and 2024, the research team recruited 153 newly diagnosed HCC cases with different etiologies and 170 patients with MASLD but without HCC from Baylor College of Medicine’s outpatient clinics. For this study, they selected 47 age- and sex-matched pairs, all of whom had cirrhosis. Only those with a history of hypertension were included, however. Data on risk factors of metabolic syndrome (including diabetes) and HCC were collected, along with details about medication use such as metformin and statins.

A total of 42 patients with MASLD and HCC and 39 MASLD control individuals had a history of hypertension and were treated with antihypertensive medications. The mean age was 66.5 years for the HCC group and 63.5 years for the control group, and the mean body mass index (BMI) was 31.1 for the HCC group and 31.7 for the control group.

After adjusting for age, sex, BMI, Hispanic ethnicity, and use of other medications, patients taking CCBs had an increased HCC risk (odds ratio [OR], 2.76), compared with those not taking CCBs. Patients taking ACE inhibitors or ARBs also had an increased HCC risk (OR, 2.54), compared with those not taking ACE inhibitors or ARBs.

However, there wasn’t a statistically significant difference in HCC risk among patients taking beta-blockers (OR, 0.87).

“Patients with fatty liver in the presence of metabolic syndrome, especially in the presence of cirrhosis and antihypertensives, need to have stricter surveillance for liver cancer,” Elhariri said.

“We need to carefully review blood pressure medications in patients with MASLD and cirrhosis,” he said. CCBs, ACE inhibitors, and ARBs can be replaced with beta-blockers, “which have been shown to reduce progression of cirrhosis-related complications.”

 

Considering Clinical Implications

“Although our study showed some association between the use of some commonly used antihypertensives and the risk for HCC in this high-risk population, it is based on data collected retrospectively on a small number of selected patients with advanced liver disease,” Elhariri noted.

The associations and underlying mechanisms should be studied in larger populations and prospective trials, he said. “Until we have more data with a significantly larger sample size, it’s premature to raise the concern in the general population.”

“The cardiovascular benefits of controlling blood pressure far outweigh the risk of liver cancer in patients with metabolic syndrome,” Elhariri added.

In ongoing studies, researchers are investigating ways to improve patient outcomes and reduce the negative effects of cirrhosis-associated complications among patients with MASLD and metabolic dysfunction–associated steatohepatitis (MASH), Muhammad Ali Butt, MD, a hepatology fellow at Beth Israel Lahey Hospital & Medical Center in Burlington, Massachusetts, said in an interview.

Butt, who wasn’t involved with this study, presented separate research on statins in MASH patients with cirrhosis, which indicated statistically significant decreases in portal hypertension, thrombosis, hepatorenal syndrome, hepatic encephalopathy, and mortality.

“We know patients with MASLD- and MASH-associated cirrhosis commonly have other comorbidities, including high cardiovascular risks, diabetes, and hyperlipidemia,” he said. “All of these conditions indicate patients to be on other medications such as antihypertensives or statins. It’s important to know the role these medications play, especially given the high-risk profile of these patients.”

Elhariri and Butt reported no relevant disclosures.

A version of this article first appeared on Medscape.com.

SAN DIEGO — In patients with metabolic dysfunction–associated steatotic liver disease (MASLD), hypertension, and cirrhosis, certain antihypertensive medications may lead to increased risks for hepatocellular carcinoma (HCC), according to new research.

In particular, the use of calcium channel blockers (CCBs), angiotensin-converting enzyme (ACE) inhibitors, and angiotensin receptor blockers (ARBs) was associated with a higher risk of developing HCC, compared with not using these medications.

About half of patients with MASLD have hypertension, and the use of antihypertensives in these patients is beneficial to reduce the risk for cardiovascular disease and complications related to MASLD, said lead author Ahmed Elhariri, MD, a research fellow at the University of Texas MD Anderson Cancer Center, Houston, who conducted the study as a research assistant in gastroenterology and hepatology at the Baylor College of Medicine, also in Houston.

However, previous studies have suggested a possible link between these medications and cancer development, “especially CCBs and breast and lung cancer,” said Elhariri, who presented the findings at The Liver Meeting 2024: American Association for the Study of Liver Diseases (AASLD).

 

Analyzing Potential Risks

In a case-control study, Elhariri and colleagues analyzed antihypertensive medication use among patients with MASLD-induced HCC, as defined by histology or radiology based on the Liver Imaging Reporting & Data System, and control patients with MASLD but without HCC.

Between 2020 and 2024, the research team recruited 153 newly diagnosed HCC cases with different etiologies and 170 patients with MASLD but without HCC from Baylor College of Medicine’s outpatient clinics. For this study, they selected 47 age- and sex-matched pairs, all of whom had cirrhosis. Only those with a history of hypertension were included, however. Data on risk factors of metabolic syndrome (including diabetes) and HCC were collected, along with details about medication use such as metformin and statins.

A total of 42 patients with MASLD and HCC and 39 MASLD control individuals had a history of hypertension and were treated with antihypertensive medications. The mean age was 66.5 years for the HCC group and 63.5 years for the control group, and the mean body mass index (BMI) was 31.1 for the HCC group and 31.7 for the control group.

After adjusting for age, sex, BMI, Hispanic ethnicity, and use of other medications, patients taking CCBs had an increased HCC risk (odds ratio [OR], 2.76), compared with those not taking CCBs. Patients taking ACE inhibitors or ARBs also had an increased HCC risk (OR, 2.54), compared with those not taking ACE inhibitors or ARBs.

However, there wasn’t a statistically significant difference in HCC risk among patients taking beta-blockers (OR, 0.87).

“Patients with fatty liver in the presence of metabolic syndrome, especially in the presence of cirrhosis and antihypertensives, need to have stricter surveillance for liver cancer,” Elhariri said.

“We need to carefully review blood pressure medications in patients with MASLD and cirrhosis,” he said. CCBs, ACE inhibitors, and ARBs can be replaced with beta-blockers, “which have been shown to reduce progression of cirrhosis-related complications.”

 

Considering Clinical Implications

“Although our study showed some association between the use of some commonly used antihypertensives and the risk for HCC in this high-risk population, it is based on data collected retrospectively on a small number of selected patients with advanced liver disease,” Elhariri noted.

The associations and underlying mechanisms should be studied in larger populations and prospective trials, he said. “Until we have more data with a significantly larger sample size, it’s premature to raise the concern in the general population.”

“The cardiovascular benefits of controlling blood pressure far outweigh the risk of liver cancer in patients with metabolic syndrome,” Elhariri added.

In ongoing studies, researchers are investigating ways to improve patient outcomes and reduce the negative effects of cirrhosis-associated complications among patients with MASLD and metabolic dysfunction–associated steatohepatitis (MASH), Muhammad Ali Butt, MD, a hepatology fellow at Beth Israel Lahey Hospital & Medical Center in Burlington, Massachusetts, said in an interview.

Butt, who wasn’t involved with this study, presented separate research on statins in MASH patients with cirrhosis, which indicated statistically significant decreases in portal hypertension, thrombosis, hepatorenal syndrome, hepatic encephalopathy, and mortality.

“We know patients with MASLD- and MASH-associated cirrhosis commonly have other comorbidities, including high cardiovascular risks, diabetes, and hyperlipidemia,” he said. “All of these conditions indicate patients to be on other medications such as antihypertensives or statins. It’s important to know the role these medications play, especially given the high-risk profile of these patients.”

Elhariri and Butt reported no relevant disclosures.

A version of this article first appeared on Medscape.com.

SAN DIEGO — In patients with metabolic dysfunction–associated steatotic liver disease (MASLD), hypertension, and cirrhosis, certain antihypertensive medications may lead to increased risks for hepatocellular carcinoma (HCC), according to new research.

In particular, the use of calcium channel blockers (CCBs), angiotensin-converting enzyme (ACE) inhibitors, and angiotensin receptor blockers (ARBs) was associated with a higher risk of developing HCC, compared with not using these medications.

About half of patients with MASLD have hypertension, and the use of antihypertensives in these patients is beneficial to reduce the risk for cardiovascular disease and complications related to MASLD, said lead author Ahmed Elhariri, MD, a research fellow at the University of Texas MD Anderson Cancer Center, Houston, who conducted the study as a research assistant in gastroenterology and hepatology at the Baylor College of Medicine, also in Houston.

However, previous studies have suggested a possible link between these medications and cancer development, “especially CCBs and breast and lung cancer,” said Elhariri, who presented the findings at The Liver Meeting 2024: American Association for the Study of Liver Diseases (AASLD).

 

Analyzing Potential Risks

In a case-control study, Elhariri and colleagues analyzed antihypertensive medication use among patients with MASLD-induced HCC, as defined by histology or radiology based on the Liver Imaging Reporting & Data System, and control patients with MASLD but without HCC.

Between 2020 and 2024, the research team recruited 153 newly diagnosed HCC cases with different etiologies and 170 patients with MASLD but without HCC from Baylor College of Medicine’s outpatient clinics. For this study, they selected 47 age- and sex-matched pairs, all of whom had cirrhosis. Only those with a history of hypertension were included, however. Data on risk factors of metabolic syndrome (including diabetes) and HCC were collected, along with details about medication use such as metformin and statins.

A total of 42 patients with MASLD and HCC and 39 MASLD control individuals had a history of hypertension and were treated with antihypertensive medications. The mean age was 66.5 years for the HCC group and 63.5 years for the control group, and the mean body mass index (BMI) was 31.1 for the HCC group and 31.7 for the control group.

After adjusting for age, sex, BMI, Hispanic ethnicity, and use of other medications, patients taking CCBs had an increased HCC risk (odds ratio [OR], 2.76), compared with those not taking CCBs. Patients taking ACE inhibitors or ARBs also had an increased HCC risk (OR, 2.54), compared with those not taking ACE inhibitors or ARBs.

However, there wasn’t a statistically significant difference in HCC risk among patients taking beta-blockers (OR, 0.87).

“Patients with fatty liver in the presence of metabolic syndrome, especially in the presence of cirrhosis and antihypertensives, need to have stricter surveillance for liver cancer,” Elhariri said.

“We need to carefully review blood pressure medications in patients with MASLD and cirrhosis,” he said. CCBs, ACE inhibitors, and ARBs can be replaced with beta-blockers, “which have been shown to reduce progression of cirrhosis-related complications.”

 

Considering Clinical Implications

“Although our study showed some association between the use of some commonly used antihypertensives and the risk for HCC in this high-risk population, it is based on data collected retrospectively on a small number of selected patients with advanced liver disease,” Elhariri noted.

The associations and underlying mechanisms should be studied in larger populations and prospective trials, he said. “Until we have more data with a significantly larger sample size, it’s premature to raise the concern in the general population.”

“The cardiovascular benefits of controlling blood pressure far outweigh the risk of liver cancer in patients with metabolic syndrome,” Elhariri added.

In ongoing studies, researchers are investigating ways to improve patient outcomes and reduce the negative effects of cirrhosis-associated complications among patients with MASLD and metabolic dysfunction–associated steatohepatitis (MASH), Muhammad Ali Butt, MD, a hepatology fellow at Beth Israel Lahey Hospital & Medical Center in Burlington, Massachusetts, said in an interview.

Butt, who wasn’t involved with this study, presented separate research on statins in MASH patients with cirrhosis, which indicated statistically significant decreases in portal hypertension, thrombosis, hepatorenal syndrome, hepatic encephalopathy, and mortality.

“We know patients with MASLD- and MASH-associated cirrhosis commonly have other comorbidities, including high cardiovascular risks, diabetes, and hyperlipidemia,” he said. “All of these conditions indicate patients to be on other medications such as antihypertensives or statins. It’s important to know the role these medications play, especially given the high-risk profile of these patients.”

Elhariri and Butt reported no relevant disclosures.

A version of this article first appeared on Medscape.com.

NEW YORK CITY — Instructions on wound healing often involve disturbing photographs of severe diabetic ulcers, angry autoimmune blistering, and oozing lesions produced by uncommon genetic disorders, but whether or not they are dramatic, day-to-day dermatologic wound care relies on both the basics as well as novel approaches, according to a well-known wound treatment expert.

Wound repair is relevant to any specialty involved in invasive interventions, but dermatologists are at ground zero and should have commensurate skills, suggested Robert S. Kirsner, MD, PhD, director of the Wound Clinic at Jackson Memorial Hospital and chair of the Department of Dermatology and Cutaneous Surgery at the University of Miami, Florida.

“We as a specialty make and repair more wounds than any other specialty,” said Kirsner, who provided data to make his point. In a table he showed, the number of wound repairs made annually by dermatologists was several-fold higher than surgeons, the next highest group, and the numbers declined rapidly from there. 

Speaking at the 27th Annual Winter Symposium – Advances in Medical and Surgical Dermatology (MSWS) 2024, Kirsner offered an array of clinical pearls, reinforced some basics, and pointed to well-supported strategies he believes are too often overlooked.

Drugs Repurposed for Wound Healing

Of the clinical pearls, he spoke of the repurposing of several agents for wound care. His first example was the monoclonal antibody dupilumab, which inhibits interleukin-4 (IL-4) and IL-13 signaling, to heal selected patients with leg ulcers. The potential of this drug for wound healing was based on a patient with a leg ulcer who presented with concomitant prurigo nodularis and biliary cirrhosis. When offered for the comorbidities, dupilumab provided a “dramatic” benefit with regard to the wound, according to Kirsner. 

The explanation for the response is that IL-4 and IL-13 have been found to be upregulated in some patients with leg ulcers. Based on numerous cases, Kirsner spoke of a phenotype of nonhealing leg ulcers from which elevated IL-4 and IL-13 can be isolated; these are the candidates for adding dupilumab to wound care, he said.

Topical beta-blockade is another example of a therapy repurposed for wound healing, according to Kirsner. He said beta-blockers are already a standard of care for burn wounds, but the mechanism is relevant in other wound types.

Several studies have looked at this phenomenon, with experimental studies showing that skin healing is impaired when beta-2 receptors are agonized but accelerated when blocked. 

 

Beta-Blockade Accelerates Wound Healing 

A recent review of these mechanisms in soft-tissue wound healing pointed to an anti-inflammatory effect, acceleration of keratinocyte migration, pro-reepithelization effects, and inhibition of bacterial virulence. Beta-blockers were first implicated as mediators of wound healing more than a decade ago, but Kirsner indicated that there is now more attention to this therapy within a comprehensive approach in difficult cases.

Although not specific to wound healing, the potential for teprotumumab to improve control of pretibial myxedema is another example of a repurposed therapy for a challenging skin disease. Teprotumumab, a monoclonal antibody that targets the insulin-like growth factor-1 (IGF-1) receptor, is approved for active thyroid eye disease, but Kirsner cited data showing compelling evidence of benefit in this cutaneous complication of Graves disease.

As for basics, Kirsner devoted some time to emphasizing the importance of compression therapy for improving leg vascularization. This is not something to just consider; rather, he thinks it is part of standard practice. “Compress all leg ulcers,” was Kirsner’s simple message.

Citing encouraging work in identifying targetable molecular events in wound healing, Kirsner suggested that treatment might be increasingly guided by biomarkers. He pointed to ongoing work to characterize wound exudate as a source of biomarkers.

“The discarded dressing contains a wealth of information,” he said, referring to cell types and proteins, such as growth factors. He thinks that the ongoing studies of exudate, which have shown that molecular processes detected at the periphery are often different than those at the focal site of injury, have substantial promise for identifying new treatment targets.

 

Virtual Reality to Address Pain

From a practical standpoint, Kirsner looked to a well-studied but still underused adjunct to wound debridement and surgical repair: the distraction offered by relatively low-priced virtual reality systems. He described it as a simple way to help patients keep their minds off the pain. It is not a new idea and has been studied for this use numerous times, and the evidence of benefit is essentially uniform, according to Kirsner.

He said effective and sophisticated systems can now be purchased for just hundreds of dollars, and no training is needed. Indeed, he said pediatric patients can typically explain how the system works if the clinician does not know.

“If you can enhance their experience [during wound repair], you can make their lives and your life better,” he said. 

Joshua Zeichner, MD, associate professor of dermatology at Mount Sinai Hospital in New York City, concurred that the evidence supports this approach and is easy to do. “I am in favor of anything that improves the experience of the patient,” said Zeichner, who chaired the portion of the meeting during which Kirsner spoke. 

Kirsner said he practices what he preaches. “I routinely employ virtual reality for simple surgical procedures or processes that patients might find unpleasant,” he said. He acknowledged that clinicians might have heard this message before, but he believes those who have not yet introduced this into their practice should consider it.

Kirsner has reported no relevant financial relationships. Zeichner has reported serving as a consultant for Beiersdorf. 

A version of this article first appeared on Medscape.com.

NEW YORK CITY — Instructions on wound healing often involve disturbing photographs of severe diabetic ulcers, angry autoimmune blistering, and oozing lesions produced by uncommon genetic disorders, but whether or not they are dramatic, day-to-day dermatologic wound care relies on both the basics as well as novel approaches, according to a well-known wound treatment expert.

Wound repair is relevant to any specialty involved in invasive interventions, but dermatologists are at ground zero and should have commensurate skills, suggested Robert S. Kirsner, MD, PhD, director of the Wound Clinic at Jackson Memorial Hospital and chair of the Department of Dermatology and Cutaneous Surgery at the University of Miami, Florida.

“We as a specialty make and repair more wounds than any other specialty,” said Kirsner, who provided data to make his point. In a table he showed, the number of wound repairs made annually by dermatologists was several-fold higher than surgeons, the next highest group, and the numbers declined rapidly from there. 

Speaking at the 27th Annual Winter Symposium – Advances in Medical and Surgical Dermatology (MSWS) 2024, Kirsner offered an array of clinical pearls, reinforced some basics, and pointed to well-supported strategies he believes are too often overlooked.

Drugs Repurposed for Wound Healing

Of the clinical pearls, he spoke of the repurposing of several agents for wound care. His first example was the monoclonal antibody dupilumab, which inhibits interleukin-4 (IL-4) and IL-13 signaling, to heal selected patients with leg ulcers. The potential of this drug for wound healing was based on a patient with a leg ulcer who presented with concomitant prurigo nodularis and biliary cirrhosis. When offered for the comorbidities, dupilumab provided a “dramatic” benefit with regard to the wound, according to Kirsner. 

The explanation for the response is that IL-4 and IL-13 have been found to be upregulated in some patients with leg ulcers. Based on numerous cases, Kirsner spoke of a phenotype of nonhealing leg ulcers from which elevated IL-4 and IL-13 can be isolated; these are the candidates for adding dupilumab to wound care, he said.

Topical beta-blockade is another example of a therapy repurposed for wound healing, according to Kirsner. He said beta-blockers are already a standard of care for burn wounds, but the mechanism is relevant in other wound types.

Several studies have looked at this phenomenon, with experimental studies showing that skin healing is impaired when beta-2 receptors are agonized but accelerated when blocked. 

 

Beta-Blockade Accelerates Wound Healing 

A recent review of these mechanisms in soft-tissue wound healing pointed to an anti-inflammatory effect, acceleration of keratinocyte migration, pro-reepithelization effects, and inhibition of bacterial virulence. Beta-blockers were first implicated as mediators of wound healing more than a decade ago, but Kirsner indicated that there is now more attention to this therapy within a comprehensive approach in difficult cases.

Although not specific to wound healing, the potential for teprotumumab to improve control of pretibial myxedema is another example of a repurposed therapy for a challenging skin disease. Teprotumumab, a monoclonal antibody that targets the insulin-like growth factor-1 (IGF-1) receptor, is approved for active thyroid eye disease, but Kirsner cited data showing compelling evidence of benefit in this cutaneous complication of Graves disease.

As for basics, Kirsner devoted some time to emphasizing the importance of compression therapy for improving leg vascularization. This is not something to just consider; rather, he thinks it is part of standard practice. “Compress all leg ulcers,” was Kirsner’s simple message.

Citing encouraging work in identifying targetable molecular events in wound healing, Kirsner suggested that treatment might be increasingly guided by biomarkers. He pointed to ongoing work to characterize wound exudate as a source of biomarkers.

“The discarded dressing contains a wealth of information,” he said, referring to cell types and proteins, such as growth factors. He thinks that the ongoing studies of exudate, which have shown that molecular processes detected at the periphery are often different than those at the focal site of injury, have substantial promise for identifying new treatment targets.

 

Virtual Reality to Address Pain

From a practical standpoint, Kirsner looked to a well-studied but still underused adjunct to wound debridement and surgical repair: the distraction offered by relatively low-priced virtual reality systems. He described it as a simple way to help patients keep their minds off the pain. It is not a new idea and has been studied for this use numerous times, and the evidence of benefit is essentially uniform, according to Kirsner.

He said effective and sophisticated systems can now be purchased for just hundreds of dollars, and no training is needed. Indeed, he said pediatric patients can typically explain how the system works if the clinician does not know.

“If you can enhance their experience [during wound repair], you can make their lives and your life better,” he said. 

Joshua Zeichner, MD, associate professor of dermatology at Mount Sinai Hospital in New York City, concurred that the evidence supports this approach and is easy to do. “I am in favor of anything that improves the experience of the patient,” said Zeichner, who chaired the portion of the meeting during which Kirsner spoke. 

Kirsner said he practices what he preaches. “I routinely employ virtual reality for simple surgical procedures or processes that patients might find unpleasant,” he said. He acknowledged that clinicians might have heard this message before, but he believes those who have not yet introduced this into their practice should consider it.

Kirsner has reported no relevant financial relationships. Zeichner has reported serving as a consultant for Beiersdorf. 

A version of this article first appeared on Medscape.com.

NEW YORK CITY — Instructions on wound healing often involve disturbing photographs of severe diabetic ulcers, angry autoimmune blistering, and oozing lesions produced by uncommon genetic disorders, but whether or not they are dramatic, day-to-day dermatologic wound care relies on both the basics as well as novel approaches, according to a well-known wound treatment expert.

Wound repair is relevant to any specialty involved in invasive interventions, but dermatologists are at ground zero and should have commensurate skills, suggested Robert S. Kirsner, MD, PhD, director of the Wound Clinic at Jackson Memorial Hospital and chair of the Department of Dermatology and Cutaneous Surgery at the University of Miami, Florida.

“We as a specialty make and repair more wounds than any other specialty,” said Kirsner, who provided data to make his point. In a table he showed, the number of wound repairs made annually by dermatologists was several-fold higher than surgeons, the next highest group, and the numbers declined rapidly from there. 

Speaking at the 27th Annual Winter Symposium – Advances in Medical and Surgical Dermatology (MSWS) 2024, Kirsner offered an array of clinical pearls, reinforced some basics, and pointed to well-supported strategies he believes are too often overlooked.

Drugs Repurposed for Wound Healing

Of the clinical pearls, he spoke of the repurposing of several agents for wound care. His first example was the monoclonal antibody dupilumab, which inhibits interleukin-4 (IL-4) and IL-13 signaling, to heal selected patients with leg ulcers. The potential of this drug for wound healing was based on a patient with a leg ulcer who presented with concomitant prurigo nodularis and biliary cirrhosis. When offered for the comorbidities, dupilumab provided a “dramatic” benefit with regard to the wound, according to Kirsner. 

The explanation for the response is that IL-4 and IL-13 have been found to be upregulated in some patients with leg ulcers. Based on numerous cases, Kirsner spoke of a phenotype of nonhealing leg ulcers from which elevated IL-4 and IL-13 can be isolated; these are the candidates for adding dupilumab to wound care, he said.

Topical beta-blockade is another example of a therapy repurposed for wound healing, according to Kirsner. He said beta-blockers are already a standard of care for burn wounds, but the mechanism is relevant in other wound types.

Several studies have looked at this phenomenon, with experimental studies showing that skin healing is impaired when beta-2 receptors are agonized but accelerated when blocked. 

 

Beta-Blockade Accelerates Wound Healing 

A recent review of these mechanisms in soft-tissue wound healing pointed to an anti-inflammatory effect, acceleration of keratinocyte migration, pro-reepithelization effects, and inhibition of bacterial virulence. Beta-blockers were first implicated as mediators of wound healing more than a decade ago, but Kirsner indicated that there is now more attention to this therapy within a comprehensive approach in difficult cases.

Although not specific to wound healing, the potential for teprotumumab to improve control of pretibial myxedema is another example of a repurposed therapy for a challenging skin disease. Teprotumumab, a monoclonal antibody that targets the insulin-like growth factor-1 (IGF-1) receptor, is approved for active thyroid eye disease, but Kirsner cited data showing compelling evidence of benefit in this cutaneous complication of Graves disease.

As for basics, Kirsner devoted some time to emphasizing the importance of compression therapy for improving leg vascularization. This is not something to just consider; rather, he thinks it is part of standard practice. “Compress all leg ulcers,” was Kirsner’s simple message.

Citing encouraging work in identifying targetable molecular events in wound healing, Kirsner suggested that treatment might be increasingly guided by biomarkers. He pointed to ongoing work to characterize wound exudate as a source of biomarkers.

“The discarded dressing contains a wealth of information,” he said, referring to cell types and proteins, such as growth factors. He thinks that the ongoing studies of exudate, which have shown that molecular processes detected at the periphery are often different than those at the focal site of injury, have substantial promise for identifying new treatment targets.

 

Virtual Reality to Address Pain

From a practical standpoint, Kirsner looked to a well-studied but still underused adjunct to wound debridement and surgical repair: the distraction offered by relatively low-priced virtual reality systems. He described it as a simple way to help patients keep their minds off the pain. It is not a new idea and has been studied for this use numerous times, and the evidence of benefit is essentially uniform, according to Kirsner.

He said effective and sophisticated systems can now be purchased for just hundreds of dollars, and no training is needed. Indeed, he said pediatric patients can typically explain how the system works if the clinician does not know.

“If you can enhance their experience [during wound repair], you can make their lives and your life better,” he said. 

Joshua Zeichner, MD, associate professor of dermatology at Mount Sinai Hospital in New York City, concurred that the evidence supports this approach and is easy to do. “I am in favor of anything that improves the experience of the patient,” said Zeichner, who chaired the portion of the meeting during which Kirsner spoke. 

Kirsner said he practices what he preaches. “I routinely employ virtual reality for simple surgical procedures or processes that patients might find unpleasant,” he said. He acknowledged that clinicians might have heard this message before, but he believes those who have not yet introduced this into their practice should consider it.

Kirsner has reported no relevant financial relationships. Zeichner has reported serving as a consultant for Beiersdorf. 

A version of this article first appeared on Medscape.com.

TOPLINE:

Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) and fenofibrates are associated with a reduced risk for diabetic macular edema (DME) in patients with type 2 diabetes, while calcium channel blockers appear to increase the risk.

METHODOLOGY:

• Researchers conducted a retrospective analysis of electronic medical records from the TriNetX health research network to evaluate how systemic medications, such as GLP-1 RAs, fenofibrates, thiazolidinediones, and calcium channel blockers, influence the risk of developing DME in patients with type 2 diabetes.
• They included patients with a 5-year history of type 2 diabetes and an absence of DME at baseline.
• The treatment group included patients who initiated treatment with calcium channel blockers (n = 107,193), GLP-1 RAs (n = 76,583), thiazolidinediones (n = 25,657), or fenofibrates (n = 18,606) after a diagnosis of diabetes. The control group received none of these medications within 1 year of being diagnosed with the condition.
• The researchers used propensity score matching to balance baseline characteristics and comorbidities between both groups.
• The primary outcome was the incidence of diagnoses of DME within a 2-year follow-up period after the initiation of systemic medications.

TAKEAWAY:

• Patients treated with calcium channel blockers showed an increased risk for incident DME (hazard ratio [HR], 1.66; 95% CI, 1.54-1.78) compared with control individuals.
• Treatment with GLP-1 RAs was associated with a reduced risk for DME (HR, 0.77; 95% CI, 0.70-0.85), as was treatment with fenofibrates (HR, 0.83; 95% CI, 0.68-0.98).
• No significant difference in risk for DME was observed between patients taking thiazolidinediones and control individuals.

IN PRACTICE:

“We found a possible protective effect for GLP-1 RA medications and fenofibrate for DME and an adverse effect for calcium channel blockers with regard to the development of DME in patients” with type 2 diabetes, the authors wrote.

“Our preliminary data suggests a protective effect with regard to GLP-1 RA drugs and the development of DME. Clinical studies examining a potential therapeutic effect of GLP-1 RA drugs on DME do seem warranted. A single orally administered drug could conceivably lower blood sugar, reduce weight, offer cardiovascular protection, and treat DME” in patients with type 2 diabetes, they added.

 

SOURCE:

The study was led by Jawad Muayad, BS, of the School of Medicine at Texas A&M University, in Houston. It was published online on December 5, 2024, in Ophthalmology Retina.

LIMITATIONS:

The study was retrospective in nature. It relied on electronic medical records for the diagnosis of DME instead of directly assessing retinal images or measuring retinal thickness. Moreover, patients on certain medications may have been monitored more closely, potentially influencing the likelihood of a diagnosis of DME being recorded.

DISCLOSURES:

The study did not receive any funding support. One author disclosed receiving consulting fees from various institutions and pharmaceutical companies. The other authors reported no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) and fenofibrates are associated with a reduced risk for diabetic macular edema (DME) in patients with type 2 diabetes, while calcium channel blockers appear to increase the risk.

METHODOLOGY:

• Researchers conducted a retrospective analysis of electronic medical records from the TriNetX health research network to evaluate how systemic medications, such as GLP-1 RAs, fenofibrates, thiazolidinediones, and calcium channel blockers, influence the risk of developing DME in patients with type 2 diabetes.
• They included patients with a 5-year history of type 2 diabetes and an absence of DME at baseline.
• The treatment group included patients who initiated treatment with calcium channel blockers (n = 107,193), GLP-1 RAs (n = 76,583), thiazolidinediones (n = 25,657), or fenofibrates (n = 18,606) after a diagnosis of diabetes. The control group received none of these medications within 1 year of being diagnosed with the condition.
• The researchers used propensity score matching to balance baseline characteristics and comorbidities between both groups.
• The primary outcome was the incidence of diagnoses of DME within a 2-year follow-up period after the initiation of systemic medications.

TAKEAWAY:

• Patients treated with calcium channel blockers showed an increased risk for incident DME (hazard ratio [HR], 1.66; 95% CI, 1.54-1.78) compared with control individuals.
• Treatment with GLP-1 RAs was associated with a reduced risk for DME (HR, 0.77; 95% CI, 0.70-0.85), as was treatment with fenofibrates (HR, 0.83; 95% CI, 0.68-0.98).
• No significant difference in risk for DME was observed between patients taking thiazolidinediones and control individuals.

IN PRACTICE:

“We found a possible protective effect for GLP-1 RA medications and fenofibrate for DME and an adverse effect for calcium channel blockers with regard to the development of DME in patients” with type 2 diabetes, the authors wrote.

“Our preliminary data suggests a protective effect with regard to GLP-1 RA drugs and the development of DME. Clinical studies examining a potential therapeutic effect of GLP-1 RA drugs on DME do seem warranted. A single orally administered drug could conceivably lower blood sugar, reduce weight, offer cardiovascular protection, and treat DME” in patients with type 2 diabetes, they added.

 

SOURCE:

The study was led by Jawad Muayad, BS, of the School of Medicine at Texas A&M University, in Houston. It was published online on December 5, 2024, in Ophthalmology Retina.

LIMITATIONS:

The study was retrospective in nature. It relied on electronic medical records for the diagnosis of DME instead of directly assessing retinal images or measuring retinal thickness. Moreover, patients on certain medications may have been monitored more closely, potentially influencing the likelihood of a diagnosis of DME being recorded.

DISCLOSURES:

The study did not receive any funding support. One author disclosed receiving consulting fees from various institutions and pharmaceutical companies. The other authors reported no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) and fenofibrates are associated with a reduced risk for diabetic macular edema (DME) in patients with type 2 diabetes, while calcium channel blockers appear to increase the risk.

METHODOLOGY:

• Researchers conducted a retrospective analysis of electronic medical records from the TriNetX health research network to evaluate how systemic medications, such as GLP-1 RAs, fenofibrates, thiazolidinediones, and calcium channel blockers, influence the risk of developing DME in patients with type 2 diabetes.
• They included patients with a 5-year history of type 2 diabetes and an absence of DME at baseline.
• The treatment group included patients who initiated treatment with calcium channel blockers (n = 107,193), GLP-1 RAs (n = 76,583), thiazolidinediones (n = 25,657), or fenofibrates (n = 18,606) after a diagnosis of diabetes. The control group received none of these medications within 1 year of being diagnosed with the condition.
• The researchers used propensity score matching to balance baseline characteristics and comorbidities between both groups.
• The primary outcome was the incidence of diagnoses of DME within a 2-year follow-up period after the initiation of systemic medications.

TAKEAWAY:

• Patients treated with calcium channel blockers showed an increased risk for incident DME (hazard ratio [HR], 1.66; 95% CI, 1.54-1.78) compared with control individuals.
• Treatment with GLP-1 RAs was associated with a reduced risk for DME (HR, 0.77; 95% CI, 0.70-0.85), as was treatment with fenofibrates (HR, 0.83; 95% CI, 0.68-0.98).
• No significant difference in risk for DME was observed between patients taking thiazolidinediones and control individuals.

IN PRACTICE:

“We found a possible protective effect for GLP-1 RA medications and fenofibrate for DME and an adverse effect for calcium channel blockers with regard to the development of DME in patients” with type 2 diabetes, the authors wrote.

“Our preliminary data suggests a protective effect with regard to GLP-1 RA drugs and the development of DME. Clinical studies examining a potential therapeutic effect of GLP-1 RA drugs on DME do seem warranted. A single orally administered drug could conceivably lower blood sugar, reduce weight, offer cardiovascular protection, and treat DME” in patients with type 2 diabetes, they added.

 

SOURCE:

The study was led by Jawad Muayad, BS, of the School of Medicine at Texas A&M University, in Houston. It was published online on December 5, 2024, in Ophthalmology Retina.

LIMITATIONS:

The study was retrospective in nature. It relied on electronic medical records for the diagnosis of DME instead of directly assessing retinal images or measuring retinal thickness. Moreover, patients on certain medications may have been monitored more closely, potentially influencing the likelihood of a diagnosis of DME being recorded.

DISCLOSURES:

The study did not receive any funding support. One author disclosed receiving consulting fees from various institutions and pharmaceutical companies. The other authors reported no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

The updated COVID vaccines for 2024-2025 are officially here, designed to target the latest variants and offer robust protection — but getting Americans to roll up their sleeves could prove harder than ever. With COVID cases on the decline, many people feel the urgency has passed.

As of December 2, the CDC reports that COVID test positivity remains low, rising slightly to 4.5% for the week ending November 23, compared with 4.2% the previous week. That’s a far cry from the early days of 2022, when positivity rates soared above 30%. Emergency room visits for COVID now make up just 0.5%, and deaths are down to 0.8% of total weekly fatalities, compared to 1% the previous week.

This steady improvement in the numbers may explain why a recent Pew Research Center survey revealed that 6 in 10 US adults have no plans to get the updated vaccine this year.

As of December 2, according to the CDC, just 19.7% of the US adult population and 9.4% of children had gotten the updated vaccine. The age group most likely? Adults ages 65 and older, with 41.6% getting the updated shot.

Despite the good news about declining cases, our pandemic history suggests a pre-holiday increase is likely. On November 20, the CDC warned it expects levels of both COVID and RSV (respiratory syncytial virus) to rise in the coming weeks — the familiar post-Thanksgiving, pre-Christmas, and Hanukkah increase.

Here’s what to know about the 2024-2025 vaccines — what’s available, how the updated versions are tested, how well each protects you, side effects and other safety information, the best time to get them, and where.



 

What’s Available?

Three updated vaccines, which work two different ways, are authorized or licensed by the FDA for the 2024-2025 season:

Novavax. A protein subunit vaccine, Novavax is authorized for emergency use by the FDA in people ages 12 and older. The vaccine makes a protein that mimics the SARS-CoV-2 virus’ version of the spike protein and combines it with an adjuvant or “booster” to stimulate a protective immune response. This year’s version targets the JN.1 variant.

Pfizer/BioNTech. Its Comirnaty is a fully licensed vaccine for people ages 12 and older. Its mechanism of action is by messenger RNA (mRNA). It works by instructing cells to produce viral proteins, triggering an immune response. Pfizer’s COVID vaccine is authorized for emergency use in children ages 6 months to 11 years. This year’s version targets KP.2.

Moderna. Its Spikevax is a fully licensed vaccine for people ages 12 and older. It is also an mRNA vaccine. Moderna’s COVID-19 vaccine is authorized for emergency use in children ages 6 months to 11 years. This year’s version targets KP.2.

 

How Effective Are They?

Before being approved for this year’s use, each company had to show its updated vaccine is effective against the currently circulating variants. For the 2 weeks ending November 23, KP.3.1.1 and XEC, from the Omicron lineage, made up the majority of cases, according to CDC data.

How do the vaccine makers know their updated vaccines are targeting the circulating variants? The companies use “pre-clinical” data, which means the updated versions have not yet been tested in people but in other ways, such as animal studies. But they do have to prove to the FDA that their updated vaccine can neutralize the circulating variants.

Companies continue to monitor their updated vaccines as new variants appear. Later in the season, there will be more specific information about how well each vaccine protects in people after tracking real-world data.

 

What About Side Effects?

The CDC lists comparable side effects for both mRNA and protein COVID vaccines, including pain and soreness from the needle, fatigue, headache, muscle pain joint pain, chills, fever, nausea, and vomiting.

Severe allergic reactions are rare, the CDC says, but cautions to be alert for low blood pressure, swelling of the lips, tongue, or throat, or difficulty breathing.

 

Which One Is Best?

“I consider the three currently available COVID vaccines — Pfizer, Moderna, and Novavax — interchangeable,’’ said Scott Roberts, MD, an infectious diseases specialist and assistant professor of medicine at Yale School of Medicine in New Haven, Connecticut. “There have not been head-to-head studies, and the initial vaccine studies for each were performed at different phases of the pandemic, so we do not have great data to guide which one is better than another.”

He does point out the different mechanisms of action, which may make a difference in people’s choice of vaccines. “So if someone has a reaction to one of them, they can switch to a different brand.”

 

Best Time to Get It?

“We have consistently seen COVID rates rise quite significantly in the winter season, especially around the holidays. So if anyone is on the fence and hasn’t gotten the updated vaccine yet, now is a great time to get it to maximize immunity for the holidays,” he said.

What’s next? In late October, the CDC recommended a second dose of the 2024-2025 vaccine 6 months after the first one for those age 65 and above and those 6 months old and older who are moderately or severely immunocompromised.

Now, while it’s tempting to think rates are down and will continue to drop steadily, Roberts reminds people that pandemic history suggests otherwise.

 

Coverage

Most people can get COVID-19 vaccines at no cost through their private health insurance, Medicaid, or Medicare. For the uninsured, there’s also the Vaccines for Children (VFC) program or access through state and local health departments and some health centers. Find details on the CDC website.

A version of this article first appeared on WebMD.

The updated COVID vaccines for 2024-2025 are officially here, designed to target the latest variants and offer robust protection — but getting Americans to roll up their sleeves could prove harder than ever. With COVID cases on the decline, many people feel the urgency has passed.

As of December 2, the CDC reports that COVID test positivity remains low, rising slightly to 4.5% for the week ending November 23, compared with 4.2% the previous week. That’s a far cry from the early days of 2022, when positivity rates soared above 30%. Emergency room visits for COVID now make up just 0.5%, and deaths are down to 0.8% of total weekly fatalities, compared to 1% the previous week.

This steady improvement in the numbers may explain why a recent Pew Research Center survey revealed that 6 in 10 US adults have no plans to get the updated vaccine this year.

As of December 2, according to the CDC, just 19.7% of the US adult population and 9.4% of children had gotten the updated vaccine. The age group most likely? Adults ages 65 and older, with 41.6% getting the updated shot.

Despite the good news about declining cases, our pandemic history suggests a pre-holiday increase is likely. On November 20, the CDC warned it expects levels of both COVID and RSV (respiratory syncytial virus) to rise in the coming weeks — the familiar post-Thanksgiving, pre-Christmas, and Hanukkah increase.

Here’s what to know about the 2024-2025 vaccines — what’s available, how the updated versions are tested, how well each protects you, side effects and other safety information, the best time to get them, and where.



 

What’s Available?

Three updated vaccines, which work two different ways, are authorized or licensed by the FDA for the 2024-2025 season:

Novavax. A protein subunit vaccine, Novavax is authorized for emergency use by the FDA in people ages 12 and older. The vaccine makes a protein that mimics the SARS-CoV-2 virus’ version of the spike protein and combines it with an adjuvant or “booster” to stimulate a protective immune response. This year’s version targets the JN.1 variant.

Pfizer/BioNTech. Its Comirnaty is a fully licensed vaccine for people ages 12 and older. Its mechanism of action is by messenger RNA (mRNA). It works by instructing cells to produce viral proteins, triggering an immune response. Pfizer’s COVID vaccine is authorized for emergency use in children ages 6 months to 11 years. This year’s version targets KP.2.

Moderna. Its Spikevax is a fully licensed vaccine for people ages 12 and older. It is also an mRNA vaccine. Moderna’s COVID-19 vaccine is authorized for emergency use in children ages 6 months to 11 years. This year’s version targets KP.2.

 

How Effective Are They?

Before being approved for this year’s use, each company had to show its updated vaccine is effective against the currently circulating variants. For the 2 weeks ending November 23, KP.3.1.1 and XEC, from the Omicron lineage, made up the majority of cases, according to CDC data.

How do the vaccine makers know their updated vaccines are targeting the circulating variants? The companies use “pre-clinical” data, which means the updated versions have not yet been tested in people but in other ways, such as animal studies. But they do have to prove to the FDA that their updated vaccine can neutralize the circulating variants.

Companies continue to monitor their updated vaccines as new variants appear. Later in the season, there will be more specific information about how well each vaccine protects in people after tracking real-world data.

 

What About Side Effects?

The CDC lists comparable side effects for both mRNA and protein COVID vaccines, including pain and soreness from the needle, fatigue, headache, muscle pain joint pain, chills, fever, nausea, and vomiting.

Severe allergic reactions are rare, the CDC says, but cautions to be alert for low blood pressure, swelling of the lips, tongue, or throat, or difficulty breathing.

 

Which One Is Best?

“I consider the three currently available COVID vaccines — Pfizer, Moderna, and Novavax — interchangeable,’’ said Scott Roberts, MD, an infectious diseases specialist and assistant professor of medicine at Yale School of Medicine in New Haven, Connecticut. “There have not been head-to-head studies, and the initial vaccine studies for each were performed at different phases of the pandemic, so we do not have great data to guide which one is better than another.”

He does point out the different mechanisms of action, which may make a difference in people’s choice of vaccines. “So if someone has a reaction to one of them, they can switch to a different brand.”

 

Best Time to Get It?

“We have consistently seen COVID rates rise quite significantly in the winter season, especially around the holidays. So if anyone is on the fence and hasn’t gotten the updated vaccine yet, now is a great time to get it to maximize immunity for the holidays,” he said.

What’s next? In late October, the CDC recommended a second dose of the 2024-2025 vaccine 6 months after the first one for those age 65 and above and those 6 months old and older who are moderately or severely immunocompromised.

Now, while it’s tempting to think rates are down and will continue to drop steadily, Roberts reminds people that pandemic history suggests otherwise.

 

Coverage

Most people can get COVID-19 vaccines at no cost through their private health insurance, Medicaid, or Medicare. For the uninsured, there’s also the Vaccines for Children (VFC) program or access through state and local health departments and some health centers. Find details on the CDC website.

A version of this article first appeared on WebMD.

The updated COVID vaccines for 2024-2025 are officially here, designed to target the latest variants and offer robust protection — but getting Americans to roll up their sleeves could prove harder than ever. With COVID cases on the decline, many people feel the urgency has passed.

As of December 2, the CDC reports that COVID test positivity remains low, rising slightly to 4.5% for the week ending November 23, compared with 4.2% the previous week. That’s a far cry from the early days of 2022, when positivity rates soared above 30%. Emergency room visits for COVID now make up just 0.5%, and deaths are down to 0.8% of total weekly fatalities, compared to 1% the previous week.

This steady improvement in the numbers may explain why a recent Pew Research Center survey revealed that 6 in 10 US adults have no plans to get the updated vaccine this year.

As of December 2, according to the CDC, just 19.7% of the US adult population and 9.4% of children had gotten the updated vaccine. The age group most likely? Adults ages 65 and older, with 41.6% getting the updated shot.

Despite the good news about declining cases, our pandemic history suggests a pre-holiday increase is likely. On November 20, the CDC warned it expects levels of both COVID and RSV (respiratory syncytial virus) to rise in the coming weeks — the familiar post-Thanksgiving, pre-Christmas, and Hanukkah increase.

Here’s what to know about the 2024-2025 vaccines — what’s available, how the updated versions are tested, how well each protects you, side effects and other safety information, the best time to get them, and where.



 

What’s Available?

Three updated vaccines, which work two different ways, are authorized or licensed by the FDA for the 2024-2025 season:

Novavax. A protein subunit vaccine, Novavax is authorized for emergency use by the FDA in people ages 12 and older. The vaccine makes a protein that mimics the SARS-CoV-2 virus’ version of the spike protein and combines it with an adjuvant or “booster” to stimulate a protective immune response. This year’s version targets the JN.1 variant.

Pfizer/BioNTech. Its Comirnaty is a fully licensed vaccine for people ages 12 and older. Its mechanism of action is by messenger RNA (mRNA). It works by instructing cells to produce viral proteins, triggering an immune response. Pfizer’s COVID vaccine is authorized for emergency use in children ages 6 months to 11 years. This year’s version targets KP.2.

Moderna. Its Spikevax is a fully licensed vaccine for people ages 12 and older. It is also an mRNA vaccine. Moderna’s COVID-19 vaccine is authorized for emergency use in children ages 6 months to 11 years. This year’s version targets KP.2.

 

How Effective Are They?

Before being approved for this year’s use, each company had to show its updated vaccine is effective against the currently circulating variants. For the 2 weeks ending November 23, KP.3.1.1 and XEC, from the Omicron lineage, made up the majority of cases, according to CDC data.

How do the vaccine makers know their updated vaccines are targeting the circulating variants? The companies use “pre-clinical” data, which means the updated versions have not yet been tested in people but in other ways, such as animal studies. But they do have to prove to the FDA that their updated vaccine can neutralize the circulating variants.

Companies continue to monitor their updated vaccines as new variants appear. Later in the season, there will be more specific information about how well each vaccine protects in people after tracking real-world data.

 

What About Side Effects?

The CDC lists comparable side effects for both mRNA and protein COVID vaccines, including pain and soreness from the needle, fatigue, headache, muscle pain joint pain, chills, fever, nausea, and vomiting.

Severe allergic reactions are rare, the CDC says, but cautions to be alert for low blood pressure, swelling of the lips, tongue, or throat, or difficulty breathing.

 

Which One Is Best?

“I consider the three currently available COVID vaccines — Pfizer, Moderna, and Novavax — interchangeable,’’ said Scott Roberts, MD, an infectious diseases specialist and assistant professor of medicine at Yale School of Medicine in New Haven, Connecticut. “There have not been head-to-head studies, and the initial vaccine studies for each were performed at different phases of the pandemic, so we do not have great data to guide which one is better than another.”

He does point out the different mechanisms of action, which may make a difference in people’s choice of vaccines. “So if someone has a reaction to one of them, they can switch to a different brand.”

 

Best Time to Get It?

“We have consistently seen COVID rates rise quite significantly in the winter season, especially around the holidays. So if anyone is on the fence and hasn’t gotten the updated vaccine yet, now is a great time to get it to maximize immunity for the holidays,” he said.

What’s next? In late October, the CDC recommended a second dose of the 2024-2025 vaccine 6 months after the first one for those age 65 and above and those 6 months old and older who are moderately or severely immunocompromised.

Now, while it’s tempting to think rates are down and will continue to drop steadily, Roberts reminds people that pandemic history suggests otherwise.

 

Coverage

Most people can get COVID-19 vaccines at no cost through their private health insurance, Medicaid, or Medicare. For the uninsured, there’s also the Vaccines for Children (VFC) program or access through state and local health departments and some health centers. Find details on the CDC website.

A version of this article first appeared on WebMD.