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SAN ANTONIO — Weight loss treatments aren’t reaching many of the people who need them most because of coverage barriers, new data suggested.

Findings from three studies presented at The Obesity Society’s Obesity Week 2024 meeting illustrate different aspects of the problem.

One, presented by Alissa S. Chen, MD, MPH, a postdoctoral fellow at Yale University, New Haven, Connecticut, found that people with obesity, particularly those with cardiovascular disease (CVD) and those who are Black and Hispanic, have high rates of cost-related prescription drug rationing. Those findings were simultaneously published as a research letter in JAMA Network Open.

“The implications are that structural barriers impede access to medications for Black and Hispanic adults with obesity, which might worsen if there’s not expanding coverage for GLP-1 RAs [glucagon-like peptide 1 receptor agonists], and it’s possible that broader insurance coverage could ameliorate some of these issues,” Chen said.

She noted that patients don’t always volunteer that information. “In my clinical practice, I always start by saying something like, ‘I have a lot of patients who can’t afford their medications. In the last week, was there a time [you didn’t take your medications due to cost]?’ ”

State Medicaid programs vary widely in the degree to which they cover weight loss treatments. But not a single one covers all modalities — nutrition counseling (NC), intensive behavioral therapy (IBT), obesity medications (OMs), and metabolic and bariatric surgery (MBS) — without restrictions or limitations, and only seven states cover them all with restrictions, according to a dual presentation by Christine Gallagher, MPAff, associate director for research and policy with the STOP Obesity Alliance at George Washington University, Washington, DC, and Tracy Zvenyach, PhD, MS, RN, director of policy strategy and alliances at the Obesity Action Coalition, also in Washington, DC.

Detailed Medicaid coverage data for each state are posted on the STOP Obesity Alliance website. (As of now, Medicare doesn’t cover medications specifically for obesity at all.)

A third presentation, by Treah Haggerty, MD, of the Department of Family Medicine and director of the Pediatric Medical Weight Management program at West Virginia University, Morgantown, was of a qualitative descriptive study exploring the impact on 22 individuals enrolled in a medical weight loss management program whose state employee insurance carrier made a policy decision to stop covering all anti-OMs in March 2024. All had been prescribed GLP-1 agonists for weight loss, and the decision forced most to stop using them.

Those findings were published in the September 2024 issue of Obesity Pillars.

“Patients perceive the discontinuation of anti-obesity medication coverage as stigmatizing and unjust, leading to feelings of hopelessness and fear. With more insurance companies denying coverage for these costly medications, more information is needed to identify best ways to address the loss of coverage with patients. Clinical management of these patients should incorporate evidence-based obesity treatments while navigating insurance constraints,” Haggerty said.

 

Create a Safe Space to Discuss the Barriers

Asked to comment, Session Moderator John D. Clark, MD, PhD, chief population health officer at Sharp Rees-Stealy Medical Group, San Diego, California, told Medscape Medical News, “Health systems and payers are determining what can and can’t be covered, and at the end of the day, it frequently comes down to finances…I think the big challenge is really identifying patients who may have the greatest need. ... If we have limited resources, how and where should we be directing those resources? I would say the current system hasn’t really answered that question or identified patients for whom we would say that the cost truly is less than either the financial or long-term health benefits.”

But Clark said, “When some of these newer anti-obesity medications are able to go generic and be less expensive, which will happen eventually, I think things will change ... and in the future, there will be more options on the market as well.”

In the meantime, he advised that clinicians “try to have conversations with patients about these barriers, acknowledge that these barriers exist, and create a safe space to discuss those barriers. ... Let’s see where we are right now, and let’s come up with a plan.”

 

People With Obesity More Susceptible to Drug Rationing

Chen reported on a sample of 51,720 adults who participated in the 2020-2022 National Health Interview Survey who did not have diabetes and who used at least one prescription medication of any type. Of those, 80% were White, 9.7% were Hispanic, and 9.7% were Black, and 33.9% overall had obesity.

Cost-related prescription rationing, defined as any self-reported skipping, taking less, or delaying filling a prescription to save money, was reported by 8.3% of those with obesity vs 5.9% without. After adjustment, rationing among those with obesity was significantly associated with younger age (aged 18-44 years), female sex, lower incomes, lack of health insurance coverage, and CVD.

The adjusted estimated probability of cost-related prescription drug rationing was 7.4% for those with CVD vs 4.4% for those without. By race/ethnicity, the proportions reporting rationing were 7.7%, 9.8%, and 10.7% for White, Black, and Hispanics, respectively.

“Given that few insurance providers cover GLP-1 RAs for obesity, cost-related prescription drug rationing could be exacerbated if patients were prescribed GLP-1 RAs at their current price of more than $1000 a month,” Chen noted, adding that the high prices could worsen health disparities among Black and Hispanic individuals with obesity.

 

Medicaid Coverage Lacking for All Obesity Treatments

For their project, Gallagher and Zvenyach delved into a database that aggregates Medicaid manuals, fee schedules, statutes, regulations, and preferred drug lists for each US state, both for Medicaid fee for service and top Medicaid managed care plans, in order to determine 2024 levels of coverage for NC, IBT, OMs, and MBS for adults with obesity.

No state provides coverage for all those treatments without either limitations — such as body mass index (BMI) cutoffs, age, or “comorbidity regardless of body mass index (BMI)” for OM and MBS — or outright restrictions, such as “proof of failed attempts.” And only seven states provide coverage for the four modalities “with limitations”: California, Arizona, New Mexico, South Carolina, Delaware, Rhode Island, and Massachusetts.

Twenty-two states don’t cover NC, although just one state doesn’t cover IBT. Overall, 37 states don’t cover OMs, and other states ranged considerably in various restrictions and limitations for OMs and MBS. Only four states fully covered the surgery without limitations or restrictions.

“The vast majority of states have significant barriers and conditions of coverage for obesity care,” Gallagher said.

Zvenyach added, “Most of the applied exclusions, limitations, or restrictions do not align with evidence-based practice standards or guidelines.”

 

When Coverage Stops, Hopelessness and Anger Emerge

Haggerty and colleagues’ research involved semi-structured interviews of the 22 participants — all of them women — who had lost their obesity medication coverage due to their insurers’ decision. Four themes emerged:

• 1. Feelings of hope replaced by hopelessness upon loss of medication coverage: One person said, “I’m afraid for my mental health. It’s tough to be in a situation where you’re never right. And it doesn’t matter what you do; it’s not going to work, and then to have just a glimmer of hope, a little spark of hey, look, this might help. And for someone else to take that away from you for no reason. I don’t know what am I supposed to do.”
• 2. Anger regarding the perceived injustice of anti-obesity medication coverage termination: For example, “They can pay for heart attacks, they could pay for me to have a stroke, they could pay for me to have diabetes, but they won’t let me have this one medicine that could take all of that away. Makes no sense.”
• 3. Perceptions of past and present stigma within the healthcare system and insurance company: “I’m not trying for vanity. I’m way too old to be a Victoria’s Secret model. I’m not trying to do it to be cute and skinny and hot. I just want to make it through a day of work and not be exhausted.”
• 4. Generational influences on obesity treatment: “I’m married, and my husband, since I’ve started this medicine, he’s been eating better. He’s been eating what I eat, and he’s been losing weight as well.”
• Some participants said they planned to cope in different ways, including trying to obtain compounded versions of the drugs from “spas” or online pharmacies, as well as skipping doses, reducing doses, or sharing medications — in other words, rationing.

Asked by this news organization what clinicians should keep in mind, Haggerty said, “that there are big barriers and that we need to take care of the patients within this system that has their arm tied behind their back.

Chen was funded by a grant from the National Institute on Aging outside the submitted work, and she was funded as a Yale National Clinician Scholar. A coauthor received grants from the Food and Drug Administration, Johnson & Johnson, the National Institutes of Health, the Agency for Healthcare Research and Quality, and Arnold Ventures. Another coauthor reported receiving personal fees from UpToDate and the Centers for Medicare & Medicaid Services. Gallagher has received research funding from Altimmune, Amgen, Boehringer Ingelheim, Currax, Eli Lilly and Company, Found, Novo Nordisk, Pfizer, Structure Therapeutics, and WeightWatchers. Haggerty reported article publishing charge was provided by West Virginia Alliance for Creative Health Solutions. Zvenyach and Clark had no disclosures.

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

SAN ANTONIO — Weight loss treatments aren’t reaching many of the people who need them most because of coverage barriers, new data suggested.

Findings from three studies presented at The Obesity Society’s Obesity Week 2024 meeting illustrate different aspects of the problem.

One, presented by Alissa S. Chen, MD, MPH, a postdoctoral fellow at Yale University, New Haven, Connecticut, found that people with obesity, particularly those with cardiovascular disease (CVD) and those who are Black and Hispanic, have high rates of cost-related prescription drug rationing. Those findings were simultaneously published as a research letter in JAMA Network Open.

“The implications are that structural barriers impede access to medications for Black and Hispanic adults with obesity, which might worsen if there’s not expanding coverage for GLP-1 RAs [glucagon-like peptide 1 receptor agonists], and it’s possible that broader insurance coverage could ameliorate some of these issues,” Chen said.

She noted that patients don’t always volunteer that information. “In my clinical practice, I always start by saying something like, ‘I have a lot of patients who can’t afford their medications. In the last week, was there a time [you didn’t take your medications due to cost]?’ ”

State Medicaid programs vary widely in the degree to which they cover weight loss treatments. But not a single one covers all modalities — nutrition counseling (NC), intensive behavioral therapy (IBT), obesity medications (OMs), and metabolic and bariatric surgery (MBS) — without restrictions or limitations, and only seven states cover them all with restrictions, according to a dual presentation by Christine Gallagher, MPAff, associate director for research and policy with the STOP Obesity Alliance at George Washington University, Washington, DC, and Tracy Zvenyach, PhD, MS, RN, director of policy strategy and alliances at the Obesity Action Coalition, also in Washington, DC.

Detailed Medicaid coverage data for each state are posted on the STOP Obesity Alliance website. (As of now, Medicare doesn’t cover medications specifically for obesity at all.)

A third presentation, by Treah Haggerty, MD, of the Department of Family Medicine and director of the Pediatric Medical Weight Management program at West Virginia University, Morgantown, was of a qualitative descriptive study exploring the impact on 22 individuals enrolled in a medical weight loss management program whose state employee insurance carrier made a policy decision to stop covering all anti-OMs in March 2024. All had been prescribed GLP-1 agonists for weight loss, and the decision forced most to stop using them.

Those findings were published in the September 2024 issue of Obesity Pillars.

“Patients perceive the discontinuation of anti-obesity medication coverage as stigmatizing and unjust, leading to feelings of hopelessness and fear. With more insurance companies denying coverage for these costly medications, more information is needed to identify best ways to address the loss of coverage with patients. Clinical management of these patients should incorporate evidence-based obesity treatments while navigating insurance constraints,” Haggerty said.

 

Create a Safe Space to Discuss the Barriers

Asked to comment, Session Moderator John D. Clark, MD, PhD, chief population health officer at Sharp Rees-Stealy Medical Group, San Diego, California, told Medscape Medical News, “Health systems and payers are determining what can and can’t be covered, and at the end of the day, it frequently comes down to finances…I think the big challenge is really identifying patients who may have the greatest need. ... If we have limited resources, how and where should we be directing those resources? I would say the current system hasn’t really answered that question or identified patients for whom we would say that the cost truly is less than either the financial or long-term health benefits.”

But Clark said, “When some of these newer anti-obesity medications are able to go generic and be less expensive, which will happen eventually, I think things will change ... and in the future, there will be more options on the market as well.”

In the meantime, he advised that clinicians “try to have conversations with patients about these barriers, acknowledge that these barriers exist, and create a safe space to discuss those barriers. ... Let’s see where we are right now, and let’s come up with a plan.”

 

People With Obesity More Susceptible to Drug Rationing

Chen reported on a sample of 51,720 adults who participated in the 2020-2022 National Health Interview Survey who did not have diabetes and who used at least one prescription medication of any type. Of those, 80% were White, 9.7% were Hispanic, and 9.7% were Black, and 33.9% overall had obesity.

Cost-related prescription rationing, defined as any self-reported skipping, taking less, or delaying filling a prescription to save money, was reported by 8.3% of those with obesity vs 5.9% without. After adjustment, rationing among those with obesity was significantly associated with younger age (aged 18-44 years), female sex, lower incomes, lack of health insurance coverage, and CVD.

The adjusted estimated probability of cost-related prescription drug rationing was 7.4% for those with CVD vs 4.4% for those without. By race/ethnicity, the proportions reporting rationing were 7.7%, 9.8%, and 10.7% for White, Black, and Hispanics, respectively.

“Given that few insurance providers cover GLP-1 RAs for obesity, cost-related prescription drug rationing could be exacerbated if patients were prescribed GLP-1 RAs at their current price of more than $1000 a month,” Chen noted, adding that the high prices could worsen health disparities among Black and Hispanic individuals with obesity.

 

Medicaid Coverage Lacking for All Obesity Treatments

For their project, Gallagher and Zvenyach delved into a database that aggregates Medicaid manuals, fee schedules, statutes, regulations, and preferred drug lists for each US state, both for Medicaid fee for service and top Medicaid managed care plans, in order to determine 2024 levels of coverage for NC, IBT, OMs, and MBS for adults with obesity.

No state provides coverage for all those treatments without either limitations — such as body mass index (BMI) cutoffs, age, or “comorbidity regardless of body mass index (BMI)” for OM and MBS — or outright restrictions, such as “proof of failed attempts.” And only seven states provide coverage for the four modalities “with limitations”: California, Arizona, New Mexico, South Carolina, Delaware, Rhode Island, and Massachusetts.

Twenty-two states don’t cover NC, although just one state doesn’t cover IBT. Overall, 37 states don’t cover OMs, and other states ranged considerably in various restrictions and limitations for OMs and MBS. Only four states fully covered the surgery without limitations or restrictions.

“The vast majority of states have significant barriers and conditions of coverage for obesity care,” Gallagher said.

Zvenyach added, “Most of the applied exclusions, limitations, or restrictions do not align with evidence-based practice standards or guidelines.”

 

When Coverage Stops, Hopelessness and Anger Emerge

Haggerty and colleagues’ research involved semi-structured interviews of the 22 participants — all of them women — who had lost their obesity medication coverage due to their insurers’ decision. Four themes emerged:

• 1. Feelings of hope replaced by hopelessness upon loss of medication coverage: One person said, “I’m afraid for my mental health. It’s tough to be in a situation where you’re never right. And it doesn’t matter what you do; it’s not going to work, and then to have just a glimmer of hope, a little spark of hey, look, this might help. And for someone else to take that away from you for no reason. I don’t know what am I supposed to do.”
• 2. Anger regarding the perceived injustice of anti-obesity medication coverage termination: For example, “They can pay for heart attacks, they could pay for me to have a stroke, they could pay for me to have diabetes, but they won’t let me have this one medicine that could take all of that away. Makes no sense.”
• 3. Perceptions of past and present stigma within the healthcare system and insurance company: “I’m not trying for vanity. I’m way too old to be a Victoria’s Secret model. I’m not trying to do it to be cute and skinny and hot. I just want to make it through a day of work and not be exhausted.”
• 4. Generational influences on obesity treatment: “I’m married, and my husband, since I’ve started this medicine, he’s been eating better. He’s been eating what I eat, and he’s been losing weight as well.”
• Some participants said they planned to cope in different ways, including trying to obtain compounded versions of the drugs from “spas” or online pharmacies, as well as skipping doses, reducing doses, or sharing medications — in other words, rationing.

Asked by this news organization what clinicians should keep in mind, Haggerty said, “that there are big barriers and that we need to take care of the patients within this system that has their arm tied behind their back.

Chen was funded by a grant from the National Institute on Aging outside the submitted work, and she was funded as a Yale National Clinician Scholar. A coauthor received grants from the Food and Drug Administration, Johnson & Johnson, the National Institutes of Health, the Agency for Healthcare Research and Quality, and Arnold Ventures. Another coauthor reported receiving personal fees from UpToDate and the Centers for Medicare & Medicaid Services. Gallagher has received research funding from Altimmune, Amgen, Boehringer Ingelheim, Currax, Eli Lilly and Company, Found, Novo Nordisk, Pfizer, Structure Therapeutics, and WeightWatchers. Haggerty reported article publishing charge was provided by West Virginia Alliance for Creative Health Solutions. Zvenyach and Clark had no disclosures.

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

SAN ANTONIO — Weight loss treatments aren’t reaching many of the people who need them most because of coverage barriers, new data suggested.

Findings from three studies presented at The Obesity Society’s Obesity Week 2024 meeting illustrate different aspects of the problem.

One, presented by Alissa S. Chen, MD, MPH, a postdoctoral fellow at Yale University, New Haven, Connecticut, found that people with obesity, particularly those with cardiovascular disease (CVD) and those who are Black and Hispanic, have high rates of cost-related prescription drug rationing. Those findings were simultaneously published as a research letter in JAMA Network Open.

“The implications are that structural barriers impede access to medications for Black and Hispanic adults with obesity, which might worsen if there’s not expanding coverage for GLP-1 RAs [glucagon-like peptide 1 receptor agonists], and it’s possible that broader insurance coverage could ameliorate some of these issues,” Chen said.

She noted that patients don’t always volunteer that information. “In my clinical practice, I always start by saying something like, ‘I have a lot of patients who can’t afford their medications. In the last week, was there a time [you didn’t take your medications due to cost]?’ ”

State Medicaid programs vary widely in the degree to which they cover weight loss treatments. But not a single one covers all modalities — nutrition counseling (NC), intensive behavioral therapy (IBT), obesity medications (OMs), and metabolic and bariatric surgery (MBS) — without restrictions or limitations, and only seven states cover them all with restrictions, according to a dual presentation by Christine Gallagher, MPAff, associate director for research and policy with the STOP Obesity Alliance at George Washington University, Washington, DC, and Tracy Zvenyach, PhD, MS, RN, director of policy strategy and alliances at the Obesity Action Coalition, also in Washington, DC.

Detailed Medicaid coverage data for each state are posted on the STOP Obesity Alliance website. (As of now, Medicare doesn’t cover medications specifically for obesity at all.)

A third presentation, by Treah Haggerty, MD, of the Department of Family Medicine and director of the Pediatric Medical Weight Management program at West Virginia University, Morgantown, was of a qualitative descriptive study exploring the impact on 22 individuals enrolled in a medical weight loss management program whose state employee insurance carrier made a policy decision to stop covering all anti-OMs in March 2024. All had been prescribed GLP-1 agonists for weight loss, and the decision forced most to stop using them.

Those findings were published in the September 2024 issue of Obesity Pillars.

“Patients perceive the discontinuation of anti-obesity medication coverage as stigmatizing and unjust, leading to feelings of hopelessness and fear. With more insurance companies denying coverage for these costly medications, more information is needed to identify best ways to address the loss of coverage with patients. Clinical management of these patients should incorporate evidence-based obesity treatments while navigating insurance constraints,” Haggerty said.

 

Create a Safe Space to Discuss the Barriers

Asked to comment, Session Moderator John D. Clark, MD, PhD, chief population health officer at Sharp Rees-Stealy Medical Group, San Diego, California, told Medscape Medical News, “Health systems and payers are determining what can and can’t be covered, and at the end of the day, it frequently comes down to finances…I think the big challenge is really identifying patients who may have the greatest need. ... If we have limited resources, how and where should we be directing those resources? I would say the current system hasn’t really answered that question or identified patients for whom we would say that the cost truly is less than either the financial or long-term health benefits.”

But Clark said, “When some of these newer anti-obesity medications are able to go generic and be less expensive, which will happen eventually, I think things will change ... and in the future, there will be more options on the market as well.”

In the meantime, he advised that clinicians “try to have conversations with patients about these barriers, acknowledge that these barriers exist, and create a safe space to discuss those barriers. ... Let’s see where we are right now, and let’s come up with a plan.”

 

People With Obesity More Susceptible to Drug Rationing

Chen reported on a sample of 51,720 adults who participated in the 2020-2022 National Health Interview Survey who did not have diabetes and who used at least one prescription medication of any type. Of those, 80% were White, 9.7% were Hispanic, and 9.7% were Black, and 33.9% overall had obesity.

Cost-related prescription rationing, defined as any self-reported skipping, taking less, or delaying filling a prescription to save money, was reported by 8.3% of those with obesity vs 5.9% without. After adjustment, rationing among those with obesity was significantly associated with younger age (aged 18-44 years), female sex, lower incomes, lack of health insurance coverage, and CVD.

The adjusted estimated probability of cost-related prescription drug rationing was 7.4% for those with CVD vs 4.4% for those without. By race/ethnicity, the proportions reporting rationing were 7.7%, 9.8%, and 10.7% for White, Black, and Hispanics, respectively.

“Given that few insurance providers cover GLP-1 RAs for obesity, cost-related prescription drug rationing could be exacerbated if patients were prescribed GLP-1 RAs at their current price of more than $1000 a month,” Chen noted, adding that the high prices could worsen health disparities among Black and Hispanic individuals with obesity.

 

Medicaid Coverage Lacking for All Obesity Treatments

For their project, Gallagher and Zvenyach delved into a database that aggregates Medicaid manuals, fee schedules, statutes, regulations, and preferred drug lists for each US state, both for Medicaid fee for service and top Medicaid managed care plans, in order to determine 2024 levels of coverage for NC, IBT, OMs, and MBS for adults with obesity.

No state provides coverage for all those treatments without either limitations — such as body mass index (BMI) cutoffs, age, or “comorbidity regardless of body mass index (BMI)” for OM and MBS — or outright restrictions, such as “proof of failed attempts.” And only seven states provide coverage for the four modalities “with limitations”: California, Arizona, New Mexico, South Carolina, Delaware, Rhode Island, and Massachusetts.

Twenty-two states don’t cover NC, although just one state doesn’t cover IBT. Overall, 37 states don’t cover OMs, and other states ranged considerably in various restrictions and limitations for OMs and MBS. Only four states fully covered the surgery without limitations or restrictions.

“The vast majority of states have significant barriers and conditions of coverage for obesity care,” Gallagher said.

Zvenyach added, “Most of the applied exclusions, limitations, or restrictions do not align with evidence-based practice standards or guidelines.”

 

When Coverage Stops, Hopelessness and Anger Emerge

Haggerty and colleagues’ research involved semi-structured interviews of the 22 participants — all of them women — who had lost their obesity medication coverage due to their insurers’ decision. Four themes emerged:

• 1. Feelings of hope replaced by hopelessness upon loss of medication coverage: One person said, “I’m afraid for my mental health. It’s tough to be in a situation where you’re never right. And it doesn’t matter what you do; it’s not going to work, and then to have just a glimmer of hope, a little spark of hey, look, this might help. And for someone else to take that away from you for no reason. I don’t know what am I supposed to do.”
• 2. Anger regarding the perceived injustice of anti-obesity medication coverage termination: For example, “They can pay for heart attacks, they could pay for me to have a stroke, they could pay for me to have diabetes, but they won’t let me have this one medicine that could take all of that away. Makes no sense.”
• 3. Perceptions of past and present stigma within the healthcare system and insurance company: “I’m not trying for vanity. I’m way too old to be a Victoria’s Secret model. I’m not trying to do it to be cute and skinny and hot. I just want to make it through a day of work and not be exhausted.”
• 4. Generational influences on obesity treatment: “I’m married, and my husband, since I’ve started this medicine, he’s been eating better. He’s been eating what I eat, and he’s been losing weight as well.”
• Some participants said they planned to cope in different ways, including trying to obtain compounded versions of the drugs from “spas” or online pharmacies, as well as skipping doses, reducing doses, or sharing medications — in other words, rationing.

Asked by this news organization what clinicians should keep in mind, Haggerty said, “that there are big barriers and that we need to take care of the patients within this system that has their arm tied behind their back.

Chen was funded by a grant from the National Institute on Aging outside the submitted work, and she was funded as a Yale National Clinician Scholar. A coauthor received grants from the Food and Drug Administration, Johnson & Johnson, the National Institutes of Health, the Agency for Healthcare Research and Quality, and Arnold Ventures. Another coauthor reported receiving personal fees from UpToDate and the Centers for Medicare & Medicaid Services. Gallagher has received research funding from Altimmune, Amgen, Boehringer Ingelheim, Currax, Eli Lilly and Company, Found, Novo Nordisk, Pfizer, Structure Therapeutics, and WeightWatchers. Haggerty reported article publishing charge was provided by West Virginia Alliance for Creative Health Solutions. Zvenyach and Clark had no disclosures.

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

In our previous case-based review, I teased the opportunity to use biomarkers to increase the accuracy and expediency of the diagnosis of Alzheimer’s disease (AD). These tests are no longer confined to the research setting but are now available to specialists and primary care clinicians alike. Given that most cognitive disorders are first identified in primary care, however, I believe that their greatest impact will be in our clinical space.

The pathologic processes associated with AD can be detected approximately 2 decades before the advent of clinical symptoms, and the symptomatic period of cognitive impairment is estimated to occupy just the final third of the disease course of AD. Using imaging studies, primarily PET, as well as cerebrospinal fluid (CSF) and even blood biomarkers for beta amyloid and tau, the pathologic drivers of AD, clinicians can identify patients with AD pathology before any symptoms are present. Importantly for our present-day interventions, the application of biomarkers can also help to diagnose AD earlier.

Amyloid PET identifies one of the earliest markers of potential AD, but a barrier common to advanced diagnostic imaging has been cost. Medicare has now approved coverage for amyloid PET in cases of suspected cognitive impairment. In a large study of more than 16,000 older adults in the United States, PET scans were positive in 55.3% of cases with mild cognitive impairment (MCI). The PET positivity rate among adults with other dementia was 70.1%. The application of PET resulted in a change in care in more than 60% of patients with MCI and dementia. One quarter of participants had their diagnosis changed from AD to another form of dementia, and 10% were changed from a diagnosis of other dementia to AD.

Liquid biomarkers can involve either CSF or blood samples. To date, CSF testing has yielded more consistent results and has defined protocols for assessment. Still, collection of CSF is more challenging than collection of blood, and patients and their families may object to lumbar puncture. CSF assessment therefore remains generally in the province of specialists and research centers.

Primary care clinicians have been waiting for a reliable blood-based biomarker for AD, and that wait may be about to end. A study published in July 2024 included 1213 adults being evaluated for cognitive symptoms in Sweden. They completed a test measuring the ratio of phosphorylated tau 217 vs nonphosphorylated tau 217, with or without a test for serum amyloid ratios as well. These tests were compared with clinicians’ clinical diagnoses as well as CSF results, which were considered the gold standard.

Using only clinical tools, primary care clinicians’ and specialists’ diagnostic accuracy for MCI and dementia were just 61% and 73%, respectively. These values were substantially weaker vs the performance of either the serum tau or amyloid ratios (both 90% accurate). The authors concluded that serum testing has the potential to improve clinical care of patients with cognitive impairment.

Where does that leave us today? Commercially available blood biomarkers are available now which use different tests and cutoff values. These may be helpful but will probably be difficult to compare and interpret for primary care clinicians. In addition, insurance is less likely to cover these tests. Amyloid PET scans are a very reasonable option to augment clinician judgment of suspected cognitive impairment, but not all geographic areas will have ready access to this imaging study.

Still, it is an exciting time to have more objective tools at our disposal to identify MCI and AD. These tools can only be optimized by clinicians who recognize symptoms and perform the baseline testing necessary to determine pretest probability of MCI or dementia.

Charles P. Vega, Health Sciences Clinical Professor, Family Medicine, University of California, Irvine, has disclosed the following relevant financial relationships: Serve(d) as a director, officer, partner, employee, adviser, consultant, or trustee for McNeil Pharmaceuticals.

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

In our previous case-based review, I teased the opportunity to use biomarkers to increase the accuracy and expediency of the diagnosis of Alzheimer’s disease (AD). These tests are no longer confined to the research setting but are now available to specialists and primary care clinicians alike. Given that most cognitive disorders are first identified in primary care, however, I believe that their greatest impact will be in our clinical space.

The pathologic processes associated with AD can be detected approximately 2 decades before the advent of clinical symptoms, and the symptomatic period of cognitive impairment is estimated to occupy just the final third of the disease course of AD. Using imaging studies, primarily PET, as well as cerebrospinal fluid (CSF) and even blood biomarkers for beta amyloid and tau, the pathologic drivers of AD, clinicians can identify patients with AD pathology before any symptoms are present. Importantly for our present-day interventions, the application of biomarkers can also help to diagnose AD earlier.

Amyloid PET identifies one of the earliest markers of potential AD, but a barrier common to advanced diagnostic imaging has been cost. Medicare has now approved coverage for amyloid PET in cases of suspected cognitive impairment. In a large study of more than 16,000 older adults in the United States, PET scans were positive in 55.3% of cases with mild cognitive impairment (MCI). The PET positivity rate among adults with other dementia was 70.1%. The application of PET resulted in a change in care in more than 60% of patients with MCI and dementia. One quarter of participants had their diagnosis changed from AD to another form of dementia, and 10% were changed from a diagnosis of other dementia to AD.

Liquid biomarkers can involve either CSF or blood samples. To date, CSF testing has yielded more consistent results and has defined protocols for assessment. Still, collection of CSF is more challenging than collection of blood, and patients and their families may object to lumbar puncture. CSF assessment therefore remains generally in the province of specialists and research centers.

Primary care clinicians have been waiting for a reliable blood-based biomarker for AD, and that wait may be about to end. A study published in July 2024 included 1213 adults being evaluated for cognitive symptoms in Sweden. They completed a test measuring the ratio of phosphorylated tau 217 vs nonphosphorylated tau 217, with or without a test for serum amyloid ratios as well. These tests were compared with clinicians’ clinical diagnoses as well as CSF results, which were considered the gold standard.

Using only clinical tools, primary care clinicians’ and specialists’ diagnostic accuracy for MCI and dementia were just 61% and 73%, respectively. These values were substantially weaker vs the performance of either the serum tau or amyloid ratios (both 90% accurate). The authors concluded that serum testing has the potential to improve clinical care of patients with cognitive impairment.

Where does that leave us today? Commercially available blood biomarkers are available now which use different tests and cutoff values. These may be helpful but will probably be difficult to compare and interpret for primary care clinicians. In addition, insurance is less likely to cover these tests. Amyloid PET scans are a very reasonable option to augment clinician judgment of suspected cognitive impairment, but not all geographic areas will have ready access to this imaging study.

Still, it is an exciting time to have more objective tools at our disposal to identify MCI and AD. These tools can only be optimized by clinicians who recognize symptoms and perform the baseline testing necessary to determine pretest probability of MCI or dementia.

Charles P. Vega, Health Sciences Clinical Professor, Family Medicine, University of California, Irvine, has disclosed the following relevant financial relationships: Serve(d) as a director, officer, partner, employee, adviser, consultant, or trustee for McNeil Pharmaceuticals.

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

In our previous case-based review, I teased the opportunity to use biomarkers to increase the accuracy and expediency of the diagnosis of Alzheimer’s disease (AD). These tests are no longer confined to the research setting but are now available to specialists and primary care clinicians alike. Given that most cognitive disorders are first identified in primary care, however, I believe that their greatest impact will be in our clinical space.

The pathologic processes associated with AD can be detected approximately 2 decades before the advent of clinical symptoms, and the symptomatic period of cognitive impairment is estimated to occupy just the final third of the disease course of AD. Using imaging studies, primarily PET, as well as cerebrospinal fluid (CSF) and even blood biomarkers for beta amyloid and tau, the pathologic drivers of AD, clinicians can identify patients with AD pathology before any symptoms are present. Importantly for our present-day interventions, the application of biomarkers can also help to diagnose AD earlier.

Amyloid PET identifies one of the earliest markers of potential AD, but a barrier common to advanced diagnostic imaging has been cost. Medicare has now approved coverage for amyloid PET in cases of suspected cognitive impairment. In a large study of more than 16,000 older adults in the United States, PET scans were positive in 55.3% of cases with mild cognitive impairment (MCI). The PET positivity rate among adults with other dementia was 70.1%. The application of PET resulted in a change in care in more than 60% of patients with MCI and dementia. One quarter of participants had their diagnosis changed from AD to another form of dementia, and 10% were changed from a diagnosis of other dementia to AD.

Liquid biomarkers can involve either CSF or blood samples. To date, CSF testing has yielded more consistent results and has defined protocols for assessment. Still, collection of CSF is more challenging than collection of blood, and patients and their families may object to lumbar puncture. CSF assessment therefore remains generally in the province of specialists and research centers.

Primary care clinicians have been waiting for a reliable blood-based biomarker for AD, and that wait may be about to end. A study published in July 2024 included 1213 adults being evaluated for cognitive symptoms in Sweden. They completed a test measuring the ratio of phosphorylated tau 217 vs nonphosphorylated tau 217, with or without a test for serum amyloid ratios as well. These tests were compared with clinicians’ clinical diagnoses as well as CSF results, which were considered the gold standard.

Using only clinical tools, primary care clinicians’ and specialists’ diagnostic accuracy for MCI and dementia were just 61% and 73%, respectively. These values were substantially weaker vs the performance of either the serum tau or amyloid ratios (both 90% accurate). The authors concluded that serum testing has the potential to improve clinical care of patients with cognitive impairment.

Where does that leave us today? Commercially available blood biomarkers are available now which use different tests and cutoff values. These may be helpful but will probably be difficult to compare and interpret for primary care clinicians. In addition, insurance is less likely to cover these tests. Amyloid PET scans are a very reasonable option to augment clinician judgment of suspected cognitive impairment, but not all geographic areas will have ready access to this imaging study.

Still, it is an exciting time to have more objective tools at our disposal to identify MCI and AD. These tools can only be optimized by clinicians who recognize symptoms and perform the baseline testing necessary to determine pretest probability of MCI or dementia.

Charles P. Vega, Health Sciences Clinical Professor, Family Medicine, University of California, Irvine, has disclosed the following relevant financial relationships: Serve(d) as a director, officer, partner, employee, adviser, consultant, or trustee for McNeil Pharmaceuticals.

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

New recommendations from the WikiGuidelines Group offer strategies for the prevention, diagnosis, and management of urinary tract infections (UTIs) in children and adults.

While the guideline covers a range of clinical topics, including prophylaxis and antimicrobial stewardship, many key clinical questions remain unanswered because of a lack of high-quality evidence, according to lead author Zachary Nelson, PharmD, MPH, of HealthPartners and Park Nicollet Health Services, St. Louis Park, Minnesota, and colleagues.

“This guideline fills a critical gap by providing pragmatic, broadly applicable recommendations tailored for generalist care and systems-based practice,” Nelson and colleagues wrote in JAMA Network Open. “Our guidance is rooted in the best available evidence and is designed for clinicians from various backgrounds and healthcare environments. It emphasizes a patient-centered approach to the diagnosis, prevention, and treatment of UTIs and related genitourinary infections.”

The guideline panelists, including 54 experts from 12 countries, developed the document in accordance with Standards for Quality Improvement Reporting Excellence and the WikiGuidelines charter. The latter requires that “clear recommendations” are based on data from at least two concordant randomized clinical trials (RCTs), or one RCT plus one concordant prospective observational study.

This approach allowed the panel to provide clear recommendations for 6 out of 37 unique questions, while 3 other questions were partially answered. In other words, 75% of the questions lacked sufficient evidence for answers.

“These guidelines are important because they illuminate the clinical data and lack of data we have for approaching diagnosis and treatment of this common infection that leads to a wide array of morbidity and sometimes mortality, as well as significant cost burden to the healthcare system,” said coauthor Sarah Kurz, MD, clinical assistant professor of internal medicine at Michigan Medicine, Ann Arbor, in a written comment.

Jessica Hammett, MD, a urologist at Emory Healthcare, Atlanta, Georgia, who was not an author of the study, suggested that the guideline is additionally impactful because of the panel’s geographic diversity.

“It is an international collaboration that takes into account regional and international practice patterns and differences,” Hammett said in a written comment.

The key guideline recommendations are briefly summarized below.

Preventive Strategies for UTI

The guideline endorses cranberry products as preventive for UTI-prone women, children, and post-intervention patients, though data are insufficient to recommend them for older adults, those with bladder issues, or pregnant women.

Topical estrogen is recommended for postmenopausal women with recurrent UTIs, as it helps restore the vaginal microbiome with minimal systemic absorption. It may also benefit patients with breast cancer when nonhormonal alternatives fail.

For those with intact bladder anatomy, methenamine hippurate is suggested as a noninferior alternative to low-dose antibiotics for preventing recurrent UTIs.

“These findings confirm the best practice of starting postmenopausal women on vaginal estrogen to prevent UTIs, which is a treatment option that should be implemented more commonly,” Hammett said. “Interestingly as compared to the AUA guidelines, this paper recommends the use of cranberry supplementation and methenamine as antibiotic alternatives for preventing UTIs.”

 

Empirical Treatment Recommendations

According to the guideline, empirical treatment for UTIs should focus on antimicrobials with high urinary tract concentration and local pathogen efficacy.

Nitrofurantoin is recommended for uncomplicated cystitis, while trimethoprim/sulfamethoxazole (TMP/SMX) and first-generation cephalosporins are advised for pyelonephritis.

For intravenous therapy, ceftriaxone is preferred unless there are risk factors for multidrug resistance.

Recommended treatment durations include 5 days for nitrofurantoin, 3 days for TMP/SMX and fluoroquinolones, and a single dose for fosfomycin in acute cystitis cases. For acute pyelonephritis, fluoroquinolones are advised for 5-7 days, with dose-optimized beta-lactams for 7 days. Gram-negative bacteremia from urinary sources warrants a 7-day course.

 

Stewardship and Clinical Management

The guideline emphasizes antimicrobial stewardship, with support for antibiotic de-escalation and oral regimens where feasible, to reduce adverse effects and hospital stays. Although evidence is limited, the authors suggest thorough allergy assessment and selective reporting of susceptibility results to enhance antibiotic selection.

While data were insufficient to make clear recommendations about the treatment of asymptomatic bacteriuria, Nelson and colleagues suggested that this practice “risks side effects without benefit” while threatening antimicrobial sustainability.

Hammett agreed, noting that “[this] serves as an important reminder not to treat asymptomatic bacteriuria, as it increases side effects and bacterial resistance without any improvement as compared to placebo.”

 

Special Considerations for Urologic Procedures

Finally, patients undergoing urologic procedures, routine cystoscopy, and urodynamic studies generally do not require prophylactic antibiotics, according to the guideline. Single-dose antibiotic prophylaxis is recommended for low-risk nephrolithotomy patients, though high-risk individuals, such as those who are pregnant or post kidney transplant, may require extended prophylaxis.

Kurz suggested that the guideline consolidates and supports the foundation of evidence driving common practices.

“I don’t think these guidelines offer any strikingly new strategies, which is unsurprising, as they were created after a deep dive into existing literature,” Kurz said. “But more importantly, what I think they do is to highlight where and what the evidence is for many of the clinical strategies that are commonly employed. For example, in terms of prevention, it is common for primary care physicians, urologists, and infectious diseases doctors to recommend cranberry and hydration and to use methenamine. These guidelines highlight that there is sufficient quality and quantity of evidence to support these interventions.”

She also noted how the guidelines emphasize the need for symptoms to make a UTI diagnosis and advise against routine testing of asymptomatic individuals.

“Despite this not being new information, typical clinical practice is often out of step here, and this [guideline] reemphasizes the important factors when considering UTI diagnosis,” Kurz said.

Finally, she expressed frustration for the numerous knowledge gaps remaining in this area, which may be traced back to barriers ranging from the semantic to the more systemic.

“Some of the difficulty is lack of clear definitions and precise terminology regarding UTIs,” Kurz said, noting the unclear distinction between complicated and uncomplicated UTIs. “I would also argue that UTIs are a disease that predominantly affects women, and like many other diseases where this is the case, [they] tend to be less studied. Hopefully, this guideline’s spotlight on all that we do not know can inspire high-quality research to address these gaps, leading to optimal patient care along with decreased burden on the system as a whole in terms of cost and antimicrobial resistance.”

The study was funded by Merck. The WikiGuidelines Group that established this guideline is entirely voluntary and unpaid; the group intends to establish a nonprofit organization to support the development of other guidelines using this novel methodology and eventually intends to trademark the name WikiGuidelines. The authors disclosed relationships with Pfizer, Eumedica, GSK, and others.

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

New recommendations from the WikiGuidelines Group offer strategies for the prevention, diagnosis, and management of urinary tract infections (UTIs) in children and adults.

While the guideline covers a range of clinical topics, including prophylaxis and antimicrobial stewardship, many key clinical questions remain unanswered because of a lack of high-quality evidence, according to lead author Zachary Nelson, PharmD, MPH, of HealthPartners and Park Nicollet Health Services, St. Louis Park, Minnesota, and colleagues.

“This guideline fills a critical gap by providing pragmatic, broadly applicable recommendations tailored for generalist care and systems-based practice,” Nelson and colleagues wrote in JAMA Network Open. “Our guidance is rooted in the best available evidence and is designed for clinicians from various backgrounds and healthcare environments. It emphasizes a patient-centered approach to the diagnosis, prevention, and treatment of UTIs and related genitourinary infections.”

The guideline panelists, including 54 experts from 12 countries, developed the document in accordance with Standards for Quality Improvement Reporting Excellence and the WikiGuidelines charter. The latter requires that “clear recommendations” are based on data from at least two concordant randomized clinical trials (RCTs), or one RCT plus one concordant prospective observational study.

This approach allowed the panel to provide clear recommendations for 6 out of 37 unique questions, while 3 other questions were partially answered. In other words, 75% of the questions lacked sufficient evidence for answers.

“These guidelines are important because they illuminate the clinical data and lack of data we have for approaching diagnosis and treatment of this common infection that leads to a wide array of morbidity and sometimes mortality, as well as significant cost burden to the healthcare system,” said coauthor Sarah Kurz, MD, clinical assistant professor of internal medicine at Michigan Medicine, Ann Arbor, in a written comment.

Jessica Hammett, MD, a urologist at Emory Healthcare, Atlanta, Georgia, who was not an author of the study, suggested that the guideline is additionally impactful because of the panel’s geographic diversity.

“It is an international collaboration that takes into account regional and international practice patterns and differences,” Hammett said in a written comment.

The key guideline recommendations are briefly summarized below.

Preventive Strategies for UTI

The guideline endorses cranberry products as preventive for UTI-prone women, children, and post-intervention patients, though data are insufficient to recommend them for older adults, those with bladder issues, or pregnant women.

Topical estrogen is recommended for postmenopausal women with recurrent UTIs, as it helps restore the vaginal microbiome with minimal systemic absorption. It may also benefit patients with breast cancer when nonhormonal alternatives fail.

For those with intact bladder anatomy, methenamine hippurate is suggested as a noninferior alternative to low-dose antibiotics for preventing recurrent UTIs.

“These findings confirm the best practice of starting postmenopausal women on vaginal estrogen to prevent UTIs, which is a treatment option that should be implemented more commonly,” Hammett said. “Interestingly as compared to the AUA guidelines, this paper recommends the use of cranberry supplementation and methenamine as antibiotic alternatives for preventing UTIs.”

 

Empirical Treatment Recommendations

According to the guideline, empirical treatment for UTIs should focus on antimicrobials with high urinary tract concentration and local pathogen efficacy.

Nitrofurantoin is recommended for uncomplicated cystitis, while trimethoprim/sulfamethoxazole (TMP/SMX) and first-generation cephalosporins are advised for pyelonephritis.

For intravenous therapy, ceftriaxone is preferred unless there are risk factors for multidrug resistance.

Recommended treatment durations include 5 days for nitrofurantoin, 3 days for TMP/SMX and fluoroquinolones, and a single dose for fosfomycin in acute cystitis cases. For acute pyelonephritis, fluoroquinolones are advised for 5-7 days, with dose-optimized beta-lactams for 7 days. Gram-negative bacteremia from urinary sources warrants a 7-day course.

 

Stewardship and Clinical Management

The guideline emphasizes antimicrobial stewardship, with support for antibiotic de-escalation and oral regimens where feasible, to reduce adverse effects and hospital stays. Although evidence is limited, the authors suggest thorough allergy assessment and selective reporting of susceptibility results to enhance antibiotic selection.

While data were insufficient to make clear recommendations about the treatment of asymptomatic bacteriuria, Nelson and colleagues suggested that this practice “risks side effects without benefit” while threatening antimicrobial sustainability.

Hammett agreed, noting that “[this] serves as an important reminder not to treat asymptomatic bacteriuria, as it increases side effects and bacterial resistance without any improvement as compared to placebo.”

 

Special Considerations for Urologic Procedures

Finally, patients undergoing urologic procedures, routine cystoscopy, and urodynamic studies generally do not require prophylactic antibiotics, according to the guideline. Single-dose antibiotic prophylaxis is recommended for low-risk nephrolithotomy patients, though high-risk individuals, such as those who are pregnant or post kidney transplant, may require extended prophylaxis.

Kurz suggested that the guideline consolidates and supports the foundation of evidence driving common practices.

“I don’t think these guidelines offer any strikingly new strategies, which is unsurprising, as they were created after a deep dive into existing literature,” Kurz said. “But more importantly, what I think they do is to highlight where and what the evidence is for many of the clinical strategies that are commonly employed. For example, in terms of prevention, it is common for primary care physicians, urologists, and infectious diseases doctors to recommend cranberry and hydration and to use methenamine. These guidelines highlight that there is sufficient quality and quantity of evidence to support these interventions.”

She also noted how the guidelines emphasize the need for symptoms to make a UTI diagnosis and advise against routine testing of asymptomatic individuals.

“Despite this not being new information, typical clinical practice is often out of step here, and this [guideline] reemphasizes the important factors when considering UTI diagnosis,” Kurz said.

Finally, she expressed frustration for the numerous knowledge gaps remaining in this area, which may be traced back to barriers ranging from the semantic to the more systemic.

“Some of the difficulty is lack of clear definitions and precise terminology regarding UTIs,” Kurz said, noting the unclear distinction between complicated and uncomplicated UTIs. “I would also argue that UTIs are a disease that predominantly affects women, and like many other diseases where this is the case, [they] tend to be less studied. Hopefully, this guideline’s spotlight on all that we do not know can inspire high-quality research to address these gaps, leading to optimal patient care along with decreased burden on the system as a whole in terms of cost and antimicrobial resistance.”

The study was funded by Merck. The WikiGuidelines Group that established this guideline is entirely voluntary and unpaid; the group intends to establish a nonprofit organization to support the development of other guidelines using this novel methodology and eventually intends to trademark the name WikiGuidelines. The authors disclosed relationships with Pfizer, Eumedica, GSK, and others.

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

New recommendations from the WikiGuidelines Group offer strategies for the prevention, diagnosis, and management of urinary tract infections (UTIs) in children and adults.

While the guideline covers a range of clinical topics, including prophylaxis and antimicrobial stewardship, many key clinical questions remain unanswered because of a lack of high-quality evidence, according to lead author Zachary Nelson, PharmD, MPH, of HealthPartners and Park Nicollet Health Services, St. Louis Park, Minnesota, and colleagues.

“This guideline fills a critical gap by providing pragmatic, broadly applicable recommendations tailored for generalist care and systems-based practice,” Nelson and colleagues wrote in JAMA Network Open. “Our guidance is rooted in the best available evidence and is designed for clinicians from various backgrounds and healthcare environments. It emphasizes a patient-centered approach to the diagnosis, prevention, and treatment of UTIs and related genitourinary infections.”

The guideline panelists, including 54 experts from 12 countries, developed the document in accordance with Standards for Quality Improvement Reporting Excellence and the WikiGuidelines charter. The latter requires that “clear recommendations” are based on data from at least two concordant randomized clinical trials (RCTs), or one RCT plus one concordant prospective observational study.

This approach allowed the panel to provide clear recommendations for 6 out of 37 unique questions, while 3 other questions were partially answered. In other words, 75% of the questions lacked sufficient evidence for answers.

“These guidelines are important because they illuminate the clinical data and lack of data we have for approaching diagnosis and treatment of this common infection that leads to a wide array of morbidity and sometimes mortality, as well as significant cost burden to the healthcare system,” said coauthor Sarah Kurz, MD, clinical assistant professor of internal medicine at Michigan Medicine, Ann Arbor, in a written comment.

Jessica Hammett, MD, a urologist at Emory Healthcare, Atlanta, Georgia, who was not an author of the study, suggested that the guideline is additionally impactful because of the panel’s geographic diversity.

“It is an international collaboration that takes into account regional and international practice patterns and differences,” Hammett said in a written comment.

The key guideline recommendations are briefly summarized below.

Preventive Strategies for UTI

The guideline endorses cranberry products as preventive for UTI-prone women, children, and post-intervention patients, though data are insufficient to recommend them for older adults, those with bladder issues, or pregnant women.

Topical estrogen is recommended for postmenopausal women with recurrent UTIs, as it helps restore the vaginal microbiome with minimal systemic absorption. It may also benefit patients with breast cancer when nonhormonal alternatives fail.

For those with intact bladder anatomy, methenamine hippurate is suggested as a noninferior alternative to low-dose antibiotics for preventing recurrent UTIs.

“These findings confirm the best practice of starting postmenopausal women on vaginal estrogen to prevent UTIs, which is a treatment option that should be implemented more commonly,” Hammett said. “Interestingly as compared to the AUA guidelines, this paper recommends the use of cranberry supplementation and methenamine as antibiotic alternatives for preventing UTIs.”

 

Empirical Treatment Recommendations

According to the guideline, empirical treatment for UTIs should focus on antimicrobials with high urinary tract concentration and local pathogen efficacy.

Nitrofurantoin is recommended for uncomplicated cystitis, while trimethoprim/sulfamethoxazole (TMP/SMX) and first-generation cephalosporins are advised for pyelonephritis.

For intravenous therapy, ceftriaxone is preferred unless there are risk factors for multidrug resistance.

Recommended treatment durations include 5 days for nitrofurantoin, 3 days for TMP/SMX and fluoroquinolones, and a single dose for fosfomycin in acute cystitis cases. For acute pyelonephritis, fluoroquinolones are advised for 5-7 days, with dose-optimized beta-lactams for 7 days. Gram-negative bacteremia from urinary sources warrants a 7-day course.

 

Stewardship and Clinical Management

The guideline emphasizes antimicrobial stewardship, with support for antibiotic de-escalation and oral regimens where feasible, to reduce adverse effects and hospital stays. Although evidence is limited, the authors suggest thorough allergy assessment and selective reporting of susceptibility results to enhance antibiotic selection.

While data were insufficient to make clear recommendations about the treatment of asymptomatic bacteriuria, Nelson and colleagues suggested that this practice “risks side effects without benefit” while threatening antimicrobial sustainability.

Hammett agreed, noting that “[this] serves as an important reminder not to treat asymptomatic bacteriuria, as it increases side effects and bacterial resistance without any improvement as compared to placebo.”

 

Special Considerations for Urologic Procedures

Finally, patients undergoing urologic procedures, routine cystoscopy, and urodynamic studies generally do not require prophylactic antibiotics, according to the guideline. Single-dose antibiotic prophylaxis is recommended for low-risk nephrolithotomy patients, though high-risk individuals, such as those who are pregnant or post kidney transplant, may require extended prophylaxis.

Kurz suggested that the guideline consolidates and supports the foundation of evidence driving common practices.

“I don’t think these guidelines offer any strikingly new strategies, which is unsurprising, as they were created after a deep dive into existing literature,” Kurz said. “But more importantly, what I think they do is to highlight where and what the evidence is for many of the clinical strategies that are commonly employed. For example, in terms of prevention, it is common for primary care physicians, urologists, and infectious diseases doctors to recommend cranberry and hydration and to use methenamine. These guidelines highlight that there is sufficient quality and quantity of evidence to support these interventions.”

She also noted how the guidelines emphasize the need for symptoms to make a UTI diagnosis and advise against routine testing of asymptomatic individuals.

“Despite this not being new information, typical clinical practice is often out of step here, and this [guideline] reemphasizes the important factors when considering UTI diagnosis,” Kurz said.

Finally, she expressed frustration for the numerous knowledge gaps remaining in this area, which may be traced back to barriers ranging from the semantic to the more systemic.

“Some of the difficulty is lack of clear definitions and precise terminology regarding UTIs,” Kurz said, noting the unclear distinction between complicated and uncomplicated UTIs. “I would also argue that UTIs are a disease that predominantly affects women, and like many other diseases where this is the case, [they] tend to be less studied. Hopefully, this guideline’s spotlight on all that we do not know can inspire high-quality research to address these gaps, leading to optimal patient care along with decreased burden on the system as a whole in terms of cost and antimicrobial resistance.”

The study was funded by Merck. The WikiGuidelines Group that established this guideline is entirely voluntary and unpaid; the group intends to establish a nonprofit organization to support the development of other guidelines using this novel methodology and eventually intends to trademark the name WikiGuidelines. The authors disclosed relationships with Pfizer, Eumedica, GSK, and others.

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

TOPLINE:

Long-term treatment with TransCon parathyroid hormone (PTH), a replacement therapy for hypoparathyroidism, demonstrates sustained efficacy and safety in patients with hypoparathyroidism over 52 weeks, with 95% of participants able to discontinue conventional therapy.

METHODOLOGY:

• Conventional therapy for hypoparathyroidism (active vitamin D and elemental calcium) alleviates symptoms of hypocalcemia, but it does not improve insufficient PTH levels and is linked to long-term complications, such as nephrocalcinosis, nephrolithiasis, and renal dysfunction.
• This phase 3 (PaTHway) trial aimed to investigate the long-term efficacy, safety, and tolerability of TransCon PTH (palopegteriparatide) in adults with hypoparathyroidism.
• Overall, 82 patients with chronic hypoparathyroidism (mean age, 48.6 years; 78% women; 93% White) were randomly assigned to receive TransCon PTH or placebo, both coadministered with conventional therapy for 26 weeks.
• At the 26-week visit, patients who completed the blinded treatment (n = 79) were assigned to receive only TransCon PTH with conventional therapy in an ongoing 156-week open-label extension.
• For this analysis at week 52, the main efficacy endpoint was the proportion of patients (n = 78) with normal serum calcium levels (8.3-10.6 mg/dL) and independence from conventional therapy (active vitamin D and therapeutic doses of calcium); safety assessments included serum chemistries, 24-hour urine calcium excretion, and treatment-emergent adverse events.

TAKEAWAY:

• At week 52, the majority of the patients receiving TransCon PTH achieved normal serum calcium levels within the normal range (86%) and independence from conventional therapy (95%). None required active vitamin D.
• In secondary endpoints, patients receiving TransCon PTH showed sustained improvement in Hypoparathyroidism Patient Experience Scale scores, reflecting better symptom management, enhanced functioning, and overall well-being through week 52.
• At week 52, the mean 24-hour urine calcium excretion in patients first randomized to TransCon PTH was 185.1 mg/d, remaining well below the upper limit of normal (≤ 250 mg/d), while the placebo group mean fell to 223.1 mg/d during the open-label extension of TransCon PTH.
• TransCon PTH was well-tolerated, with most treatment-emergent adverse events being mild or moderate and none leading to treatment discontinuation.

IN PRACTICE:

“These results suggest that TransCon PTH may improve outcomes and advance the standard of care for adults living with hypoparathyroidism,” the authors wrote.

SOURCE:

The study was led by Bart L. Clarke, MD, Mayo Clinic, Rochester, Minnesota. It was published online in The Journal of Clinical Endocrinology & Metabolism.

LIMITATIONS:

The study’s limitations included the open-label design during the extension period, which may have introduced bias in patient-reported outcomes. Additionally, the study population was predominantly women and White, which may have limited the generalizability of the findings. Further research is needed to assess the long-term effects of TransCon PTH on renal complications. One patient died of fatal cardiac arrest deemed unrelated to the study drug.

DISCLOSURES:

The study was funded by Ascendis Pharma A/S. Seven authors declared being current or former employees of Ascendis Pharma. The other authors declared receiving grants, research funding, honoraria, serving as consultants, advisory board members, study investigators, and other ties with Ascendis Pharma and multiple other pharmaceutical companies.

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:

Long-term treatment with TransCon parathyroid hormone (PTH), a replacement therapy for hypoparathyroidism, demonstrates sustained efficacy and safety in patients with hypoparathyroidism over 52 weeks, with 95% of participants able to discontinue conventional therapy.

METHODOLOGY:

• Conventional therapy for hypoparathyroidism (active vitamin D and elemental calcium) alleviates symptoms of hypocalcemia, but it does not improve insufficient PTH levels and is linked to long-term complications, such as nephrocalcinosis, nephrolithiasis, and renal dysfunction.
• This phase 3 (PaTHway) trial aimed to investigate the long-term efficacy, safety, and tolerability of TransCon PTH (palopegteriparatide) in adults with hypoparathyroidism.
• Overall, 82 patients with chronic hypoparathyroidism (mean age, 48.6 years; 78% women; 93% White) were randomly assigned to receive TransCon PTH or placebo, both coadministered with conventional therapy for 26 weeks.
• At the 26-week visit, patients who completed the blinded treatment (n = 79) were assigned to receive only TransCon PTH with conventional therapy in an ongoing 156-week open-label extension.
• For this analysis at week 52, the main efficacy endpoint was the proportion of patients (n = 78) with normal serum calcium levels (8.3-10.6 mg/dL) and independence from conventional therapy (active vitamin D and therapeutic doses of calcium); safety assessments included serum chemistries, 24-hour urine calcium excretion, and treatment-emergent adverse events.

TAKEAWAY:

• At week 52, the majority of the patients receiving TransCon PTH achieved normal serum calcium levels within the normal range (86%) and independence from conventional therapy (95%). None required active vitamin D.
• In secondary endpoints, patients receiving TransCon PTH showed sustained improvement in Hypoparathyroidism Patient Experience Scale scores, reflecting better symptom management, enhanced functioning, and overall well-being through week 52.
• At week 52, the mean 24-hour urine calcium excretion in patients first randomized to TransCon PTH was 185.1 mg/d, remaining well below the upper limit of normal (≤ 250 mg/d), while the placebo group mean fell to 223.1 mg/d during the open-label extension of TransCon PTH.
• TransCon PTH was well-tolerated, with most treatment-emergent adverse events being mild or moderate and none leading to treatment discontinuation.

IN PRACTICE:

“These results suggest that TransCon PTH may improve outcomes and advance the standard of care for adults living with hypoparathyroidism,” the authors wrote.

SOURCE:

The study was led by Bart L. Clarke, MD, Mayo Clinic, Rochester, Minnesota. It was published online in The Journal of Clinical Endocrinology & Metabolism.

LIMITATIONS:

The study’s limitations included the open-label design during the extension period, which may have introduced bias in patient-reported outcomes. Additionally, the study population was predominantly women and White, which may have limited the generalizability of the findings. Further research is needed to assess the long-term effects of TransCon PTH on renal complications. One patient died of fatal cardiac arrest deemed unrelated to the study drug.

DISCLOSURES:

The study was funded by Ascendis Pharma A/S. Seven authors declared being current or former employees of Ascendis Pharma. The other authors declared receiving grants, research funding, honoraria, serving as consultants, advisory board members, study investigators, and other ties with Ascendis Pharma and multiple other pharmaceutical companies.

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:

Long-term treatment with TransCon parathyroid hormone (PTH), a replacement therapy for hypoparathyroidism, demonstrates sustained efficacy and safety in patients with hypoparathyroidism over 52 weeks, with 95% of participants able to discontinue conventional therapy.

METHODOLOGY:

• Conventional therapy for hypoparathyroidism (active vitamin D and elemental calcium) alleviates symptoms of hypocalcemia, but it does not improve insufficient PTH levels and is linked to long-term complications, such as nephrocalcinosis, nephrolithiasis, and renal dysfunction.
• This phase 3 (PaTHway) trial aimed to investigate the long-term efficacy, safety, and tolerability of TransCon PTH (palopegteriparatide) in adults with hypoparathyroidism.
• Overall, 82 patients with chronic hypoparathyroidism (mean age, 48.6 years; 78% women; 93% White) were randomly assigned to receive TransCon PTH or placebo, both coadministered with conventional therapy for 26 weeks.
• At the 26-week visit, patients who completed the blinded treatment (n = 79) were assigned to receive only TransCon PTH with conventional therapy in an ongoing 156-week open-label extension.
• For this analysis at week 52, the main efficacy endpoint was the proportion of patients (n = 78) with normal serum calcium levels (8.3-10.6 mg/dL) and independence from conventional therapy (active vitamin D and therapeutic doses of calcium); safety assessments included serum chemistries, 24-hour urine calcium excretion, and treatment-emergent adverse events.

TAKEAWAY:

• At week 52, the majority of the patients receiving TransCon PTH achieved normal serum calcium levels within the normal range (86%) and independence from conventional therapy (95%). None required active vitamin D.
• In secondary endpoints, patients receiving TransCon PTH showed sustained improvement in Hypoparathyroidism Patient Experience Scale scores, reflecting better symptom management, enhanced functioning, and overall well-being through week 52.
• At week 52, the mean 24-hour urine calcium excretion in patients first randomized to TransCon PTH was 185.1 mg/d, remaining well below the upper limit of normal (≤ 250 mg/d), while the placebo group mean fell to 223.1 mg/d during the open-label extension of TransCon PTH.
• TransCon PTH was well-tolerated, with most treatment-emergent adverse events being mild or moderate and none leading to treatment discontinuation.

IN PRACTICE:

“These results suggest that TransCon PTH may improve outcomes and advance the standard of care for adults living with hypoparathyroidism,” the authors wrote.

SOURCE:

The study was led by Bart L. Clarke, MD, Mayo Clinic, Rochester, Minnesota. It was published online in The Journal of Clinical Endocrinology & Metabolism.

LIMITATIONS:

The study’s limitations included the open-label design during the extension period, which may have introduced bias in patient-reported outcomes. Additionally, the study population was predominantly women and White, which may have limited the generalizability of the findings. Further research is needed to assess the long-term effects of TransCon PTH on renal complications. One patient died of fatal cardiac arrest deemed unrelated to the study drug.

DISCLOSURES:

The study was funded by Ascendis Pharma A/S. Seven authors declared being current or former employees of Ascendis Pharma. The other authors declared receiving grants, research funding, honoraria, serving as consultants, advisory board members, study investigators, and other ties with Ascendis Pharma and multiple other pharmaceutical companies.

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.

PHILADELPHIA — Gastrointestinal (GI) bleeding after percutaneous coronary intervention (PCI) among patients on dual antiplatelet therapy (DAPT) remains risky in terms of morbidity and mortality, but the Predicting Bleeding Complications in Patients Undergoing Stent Implantation and Subsequent Dual Antiplatelet Therapy (PRECISE-DAPT) score could help predict that risk, according to a study presented at the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting.

In a predominantly Hispanic population in Texas, 2.5% of post-PCI patients on DAPT had GI bleeding in the first year. The PRECISE-DAPT score helped to predict GI bleeding among high-risk and moderate-risk patients.

“Our study established that the PRECISE-DAPT score possesses a moderate predictive accuracy not only for overall bleeding risk but also specifically for gastrointestinal bleeding,” said lead author Jesus Guzman, MD, a gastroenterology fellow at the Texas Tech University Health Sciences Center El Paso.

Current guidelines from the American College of Cardiology and American Heart Association recommend DAPT for 6-12 months post-PCI, with consideration for shorter durations in patients with lower ischemic risks but higher bleeding risks.

“Interestingly, some of these patients were on DAPT for more than 2 years, which goes beyond the guidelines,” he said. “In this patient population, this has to do with them being lost to follow-up and getting reestablished, and they kept refilling their prescriptions.”

Guzman and colleagues conducted a retrospective cohort study of patients receiving DAPT after PCI from 2014 to 2021. They looked for GI bleeding rates at 1 year and across the duration of the study period, as well as endoscopic indications, findings, concurrent antiplatelet therapy, and the primary cause of bleeding.

In addition, the research team evaluated the predictive value of the PRECISE-DAPT score, which categorizes patients based on low risk (≤ 17), moderate risk (18-24), and high risk (≥ 25) for bleeding. The score aims to optimize the balance between bleeding and ischemic risks, Guzman said, by incorporating five factors: Age, creatinine clearance, hemoglobin, white blood cell count, and history of spontaneous bleeding.

Among 1067 patients, 563 (57.9%) received clopidogrel and 409 (42%) received ticagrelor. The overall cohort was 66.6% men, 77.1% Hispanic, and had a mean age of 62 years.

The GI bleeding rate was 2.5% at 1-year post-PCI among 27 patients and 3.7% for the study duration among 39 patients, with a median follow-up of 2.2 years.

Among the 39 GI bleeds, 41% were lower GI bleeds, 28% were upper GI bleeds, 15% were small bowel bleeds, and 15% were undetermined. The most frequent etiology was colon cancer, accounting for 18% of bleeds, followed by 15% for gastric ulcers, 10% for diverticular bleeds, and 10% for hemorrhoidal bleeds.

In general, analyses indicated no significant differences in GI bleeding between patients on clopidogrel (21.2%) and those on ticagrelor (19.2%).

However, the odds of GI bleeding were significantly higher in patients with high-risk PRECISE-DAPT scores (odds ratio [OR], 2.5) and moderate-risk scores (OR, 2.8) than in those with low-risk scores. The majority of patients without GI bleeding had scores < 17, whereas the majority of patients with GI bleeding had scores > 24. An optimal threshold for the PRECISE-DAPT score was identified as ≥ 19.

“When patients on DAPT present with GI bleeding, it can be a clinical conundrum for gastroenterologists and cardiologists, especially when it can be a life-or-death event, and stopping DAPT can increase risk of thrombosis,” said Jeff Taclob, MD, a hepatology fellow at The University of Tennessee Health Science Center in Memphis. Taclob, who wasn’t involved with the study, attended the conference session.

“In this population in El Paso, in particular, many patients don’t have adequate healthcare, may be lost to follow-up, and get their prescriptions filled elsewhere, such as Juárez, Mexico,” he said. “Then they come in with this life-threatening bleed, so we need to focus more on their risks.”

Paying attention to specific patient populations, cultures, and values remains important for patient communication and clinical decision-making, Taclob noted.

“In this population of older men, there’s often a macho persona where they don’t want to seek help,” he said. “DAPT criteria could differ in other populations, but here, the PRECISE-DAPT score appeared to help.”

The study was awarded the ACG Outstanding Research Award in the GI Bleeding Category (Trainee). Guzman and Taclob reported no relevant disclosures.

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

PHILADELPHIA — Gastrointestinal (GI) bleeding after percutaneous coronary intervention (PCI) among patients on dual antiplatelet therapy (DAPT) remains risky in terms of morbidity and mortality, but the Predicting Bleeding Complications in Patients Undergoing Stent Implantation and Subsequent Dual Antiplatelet Therapy (PRECISE-DAPT) score could help predict that risk, according to a study presented at the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting.

In a predominantly Hispanic population in Texas, 2.5% of post-PCI patients on DAPT had GI bleeding in the first year. The PRECISE-DAPT score helped to predict GI bleeding among high-risk and moderate-risk patients.

“Our study established that the PRECISE-DAPT score possesses a moderate predictive accuracy not only for overall bleeding risk but also specifically for gastrointestinal bleeding,” said lead author Jesus Guzman, MD, a gastroenterology fellow at the Texas Tech University Health Sciences Center El Paso.

Current guidelines from the American College of Cardiology and American Heart Association recommend DAPT for 6-12 months post-PCI, with consideration for shorter durations in patients with lower ischemic risks but higher bleeding risks.

“Interestingly, some of these patients were on DAPT for more than 2 years, which goes beyond the guidelines,” he said. “In this patient population, this has to do with them being lost to follow-up and getting reestablished, and they kept refilling their prescriptions.”

Guzman and colleagues conducted a retrospective cohort study of patients receiving DAPT after PCI from 2014 to 2021. They looked for GI bleeding rates at 1 year and across the duration of the study period, as well as endoscopic indications, findings, concurrent antiplatelet therapy, and the primary cause of bleeding.

In addition, the research team evaluated the predictive value of the PRECISE-DAPT score, which categorizes patients based on low risk (≤ 17), moderate risk (18-24), and high risk (≥ 25) for bleeding. The score aims to optimize the balance between bleeding and ischemic risks, Guzman said, by incorporating five factors: Age, creatinine clearance, hemoglobin, white blood cell count, and history of spontaneous bleeding.

Among 1067 patients, 563 (57.9%) received clopidogrel and 409 (42%) received ticagrelor. The overall cohort was 66.6% men, 77.1% Hispanic, and had a mean age of 62 years.

The GI bleeding rate was 2.5% at 1-year post-PCI among 27 patients and 3.7% for the study duration among 39 patients, with a median follow-up of 2.2 years.

Among the 39 GI bleeds, 41% were lower GI bleeds, 28% were upper GI bleeds, 15% were small bowel bleeds, and 15% were undetermined. The most frequent etiology was colon cancer, accounting for 18% of bleeds, followed by 15% for gastric ulcers, 10% for diverticular bleeds, and 10% for hemorrhoidal bleeds.

In general, analyses indicated no significant differences in GI bleeding between patients on clopidogrel (21.2%) and those on ticagrelor (19.2%).

However, the odds of GI bleeding were significantly higher in patients with high-risk PRECISE-DAPT scores (odds ratio [OR], 2.5) and moderate-risk scores (OR, 2.8) than in those with low-risk scores. The majority of patients without GI bleeding had scores < 17, whereas the majority of patients with GI bleeding had scores > 24. An optimal threshold for the PRECISE-DAPT score was identified as ≥ 19.

“When patients on DAPT present with GI bleeding, it can be a clinical conundrum for gastroenterologists and cardiologists, especially when it can be a life-or-death event, and stopping DAPT can increase risk of thrombosis,” said Jeff Taclob, MD, a hepatology fellow at The University of Tennessee Health Science Center in Memphis. Taclob, who wasn’t involved with the study, attended the conference session.

“In this population in El Paso, in particular, many patients don’t have adequate healthcare, may be lost to follow-up, and get their prescriptions filled elsewhere, such as Juárez, Mexico,” he said. “Then they come in with this life-threatening bleed, so we need to focus more on their risks.”

Paying attention to specific patient populations, cultures, and values remains important for patient communication and clinical decision-making, Taclob noted.

“In this population of older men, there’s often a macho persona where they don’t want to seek help,” he said. “DAPT criteria could differ in other populations, but here, the PRECISE-DAPT score appeared to help.”

The study was awarded the ACG Outstanding Research Award in the GI Bleeding Category (Trainee). Guzman and Taclob reported no relevant disclosures.

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

PHILADELPHIA — Gastrointestinal (GI) bleeding after percutaneous coronary intervention (PCI) among patients on dual antiplatelet therapy (DAPT) remains risky in terms of morbidity and mortality, but the Predicting Bleeding Complications in Patients Undergoing Stent Implantation and Subsequent Dual Antiplatelet Therapy (PRECISE-DAPT) score could help predict that risk, according to a study presented at the American College of Gastroenterology (ACG) 2024 Annual Scientific Meeting.

In a predominantly Hispanic population in Texas, 2.5% of post-PCI patients on DAPT had GI bleeding in the first year. The PRECISE-DAPT score helped to predict GI bleeding among high-risk and moderate-risk patients.

“Our study established that the PRECISE-DAPT score possesses a moderate predictive accuracy not only for overall bleeding risk but also specifically for gastrointestinal bleeding,” said lead author Jesus Guzman, MD, a gastroenterology fellow at the Texas Tech University Health Sciences Center El Paso.

Current guidelines from the American College of Cardiology and American Heart Association recommend DAPT for 6-12 months post-PCI, with consideration for shorter durations in patients with lower ischemic risks but higher bleeding risks.

“Interestingly, some of these patients were on DAPT for more than 2 years, which goes beyond the guidelines,” he said. “In this patient population, this has to do with them being lost to follow-up and getting reestablished, and they kept refilling their prescriptions.”

Guzman and colleagues conducted a retrospective cohort study of patients receiving DAPT after PCI from 2014 to 2021. They looked for GI bleeding rates at 1 year and across the duration of the study period, as well as endoscopic indications, findings, concurrent antiplatelet therapy, and the primary cause of bleeding.

In addition, the research team evaluated the predictive value of the PRECISE-DAPT score, which categorizes patients based on low risk (≤ 17), moderate risk (18-24), and high risk (≥ 25) for bleeding. The score aims to optimize the balance between bleeding and ischemic risks, Guzman said, by incorporating five factors: Age, creatinine clearance, hemoglobin, white blood cell count, and history of spontaneous bleeding.

Among 1067 patients, 563 (57.9%) received clopidogrel and 409 (42%) received ticagrelor. The overall cohort was 66.6% men, 77.1% Hispanic, and had a mean age of 62 years.

The GI bleeding rate was 2.5% at 1-year post-PCI among 27 patients and 3.7% for the study duration among 39 patients, with a median follow-up of 2.2 years.

Among the 39 GI bleeds, 41% were lower GI bleeds, 28% were upper GI bleeds, 15% were small bowel bleeds, and 15% were undetermined. The most frequent etiology was colon cancer, accounting for 18% of bleeds, followed by 15% for gastric ulcers, 10% for diverticular bleeds, and 10% for hemorrhoidal bleeds.

In general, analyses indicated no significant differences in GI bleeding between patients on clopidogrel (21.2%) and those on ticagrelor (19.2%).

However, the odds of GI bleeding were significantly higher in patients with high-risk PRECISE-DAPT scores (odds ratio [OR], 2.5) and moderate-risk scores (OR, 2.8) than in those with low-risk scores. The majority of patients without GI bleeding had scores < 17, whereas the majority of patients with GI bleeding had scores > 24. An optimal threshold for the PRECISE-DAPT score was identified as ≥ 19.

“When patients on DAPT present with GI bleeding, it can be a clinical conundrum for gastroenterologists and cardiologists, especially when it can be a life-or-death event, and stopping DAPT can increase risk of thrombosis,” said Jeff Taclob, MD, a hepatology fellow at The University of Tennessee Health Science Center in Memphis. Taclob, who wasn’t involved with the study, attended the conference session.

“In this population in El Paso, in particular, many patients don’t have adequate healthcare, may be lost to follow-up, and get their prescriptions filled elsewhere, such as Juárez, Mexico,” he said. “Then they come in with this life-threatening bleed, so we need to focus more on their risks.”

Paying attention to specific patient populations, cultures, and values remains important for patient communication and clinical decision-making, Taclob noted.

“In this population of older men, there’s often a macho persona where they don’t want to seek help,” he said. “DAPT criteria could differ in other populations, but here, the PRECISE-DAPT score appeared to help.”

The study was awarded the ACG Outstanding Research Award in the GI Bleeding Category (Trainee). Guzman and Taclob reported no relevant disclosures.

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

If the name of leukemia specialist Jorge Cortes, MD, appears any more often in PubMed, they’ll need to name a wing after him. 

Over 30 years, Cortes has led or coauthored hundreds of studies, including many trials of landmark drugs to treat chronic myeloid leukemia (CML). His work has helped transform CML into an often-survivable disease instead of one that took the lives of most patients within 5 years.

“It’s been remarkable to see the evolution in CML and to be part of that transition as a fellow, as faculty, and as leader of some of the trials,” said Cortes, who directs the Georgia Cancer Center at Augusta University. “I’m the luckiest person in the world.”

In an interview, Cortes talked about his youth in Mexico, his research path, and his close connections to cancer medicine in Latin America.

Q: You grew up in Mexico City. What was your family like?

A: “My father grew up very poor in a small town in Michoacán in the southwest part of Mexico. In Mexico City, he had a tiny grocery store in an old-fashioned market, and we were lower middle class.

One of the things I learned was to work hard. There’s nobody I know who worked as hard as my father. He opened his store every day of the year, [Mexican] Independence Day or New Year’s or Christmas. He worked hard so we could have a better life than he did.

We learned English from a very young age. My elementary school was called Westminster School because he wanted a school where we would learn English.

As for my mother, she stayed with us [at home] and made sure we did our homework and were taken care of. I learned about being honest and dedicating to what you were doing.”

Q: You trained at the Salvador Zubirán National Institute of Health Sciences and Nutrition in Mexico City. Then what happened? 

A: “Through encouragement by my dermatologist older brother and a mentor at the institution where I was training as a hematologist, I decided to come to the United States.

My initial focus was going to be on coagulation and thrombosis. I came to Houston (Texas) for a fellowship at the University of Texas Health Science Center.

Then I started doing my rotation for the malignant part of the fellowship at MD Anderson Cancer Center [Houston]. One of my first rotations was with Susan M. O’Brien, [MD,] who became my greatest mentor throughout my career. I really enjoyed my rotation. I thought she was great clinically, and she was doing research and teaching. That’s what I wanted for my career.”

Q: What drew you to leukemia specifically?

A: “Dr O’Brien worked in leukemia during my initial rotation, and I really loved it. It was hard work, but it was very inspiring to see the clinical research and the things you could for patients. She had a lot of joy doing that. 

I told my program director I’d change and transfer to MD Anderson, and I ended up staying at MD Anderson for 23 years.”

Q: What was leukemia research like in those days?

A: “We didn’t have the understanding of the biology and the new drugs that we have now. When I started in Mexico, we didn’t even have hydroxyurea. What we were doing was much more basic. But still, the field sounded like a great field to be involved with because they were doing so many trials and had an outstanding database. 

Because of the influence of Dr [Moshe] Talpaz, [MD,] I started getting very involved with CML. In my initial years as a young faculty, I started working with him on interferon. Then imatinib appeared. I saw even from the phase 1 study how impressive the outcomes were in patients who had no response to anything and were in bad shape.”

Q: What CML medications have you worked on?

A: “I’ve been involved with all of them. Imatinib early on, then I led trials with dasatinib and nilotinib. Then, I led the registration trials of bosutinib and ponatinib. More recently, I was part of the development of asciminib.”

Q: What were some of the biggest challenges in CML research?

A: “We had an opportunity to do a lot of analysis about TKIs [tyrosine kinase inhibitors] when these were new drugs. It was a very steep curve of learning, how to monitor and manage side effects.

Then patients were starting to have resistance to two to three TKIs. Ponatinib came along, and it was an incredibly effective drug. But after it was approved, we started to recognize the occurrence of heart attacks and strokes.

That was unexpected and not something that was known for any TKI. It was a big challenge. The drug was taken off the market for some time, and trials were put on hold by the FDA [US Food and Drug Administration].

We scrambled to understand the mechanism of action. For a year or two, it was a stressful time. But eventually we moved past it, and we learned a lot.”

Q: What sort of work have you done in Latin America?

A: “I’ve always been very close to Latin America. I have many good friends and colleagues there, and I’ve always been interested in working with them. 

We’ve done research and studies and created an organization called Latin American Leukemia Net to develop more trials in Latin America. The most rewarding thing has been the educational programs for patients that we’ve done, helping them understand the disease, the treatments, and the goals of treatment. 

We’ve conducted a number of programs, and they have been effective, well-attended, and well received. I still work with my colleagues to develop local guidelines and do collaborative research.”

Q: What convinced you to leave MD Anderson for Georgia?

A: “I never thought I’d leave MD Anderson. I had my well-oiled machine of clinical trials, my clinic, and my fellowship program. But the one thing that I wanted to see if I could try next was to develop an institution.

That was the goal here, to take the Georgia Cancer Center to NCI [National Cancer Institute] designation. So, I thought, ‘That’s a nice challenge.’ It may be a good opportunity to try a different aspect of what it means to be an oncologist.

There are days that you think, ‘What am I doing here?’ when you have to deal with budgets and personnel and all these things. But it’s part of the process. It’s still good to know that we have a goal, and that we’re going to make it. 

Also, I still see my patients, and I enjoy that I still do some research and mentoring.”

Q: What’s the current state of CML treatment?

A: “Many patients have a pretty much normal life expectancy while [on therapy]. Still, one of the goals of many patients is to stop therapy. But that’s a reality only for a small percentage of patients. How can we make that happen for more patients?”

Q: By stopping therapy, do you mean curing the cancer?

A: “Yes, pretty much. You have a good response, you stop the therapy, and it doesn’t come back.

There are also patients who really don’t do well. We hear about CML being with a disease with such a good outcome, but we have patients for whom nothing works. Is it a matter of [needing] another TKI, or do we need to look at something else?”

Q: What do you see on the horizon?

A: “We are developing new approaches like combination therapies. We’re scratching the surface on that. We need to understand which combinations work, and where and when.

And we can make more efficient uses of the drugs we have now in terms of which ones to use when, the doses, the safety profiles. I think we can do better.”

Cortes disclosed consulting for Amphivena, Astellas, Bio-Path, BioLineRx, Bristol Myers Squibb, Daiichi Sankyo, Jazz, Novartis, Pfizer, and Takeda and research funding from Astellas Pharma, Bristol Myers Squibb, Daiichi Sankyo, Immunogen, Jazz, Merus, Novartis, Pfizer, Sun Pharma, Takeda, Tolero and Trovagene.
 

A version of this article appeared on Medscape.com.

If the name of leukemia specialist Jorge Cortes, MD, appears any more often in PubMed, they’ll need to name a wing after him. 

Over 30 years, Cortes has led or coauthored hundreds of studies, including many trials of landmark drugs to treat chronic myeloid leukemia (CML). His work has helped transform CML into an often-survivable disease instead of one that took the lives of most patients within 5 years.

“It’s been remarkable to see the evolution in CML and to be part of that transition as a fellow, as faculty, and as leader of some of the trials,” said Cortes, who directs the Georgia Cancer Center at Augusta University. “I’m the luckiest person in the world.”

In an interview, Cortes talked about his youth in Mexico, his research path, and his close connections to cancer medicine in Latin America.

Q: You grew up in Mexico City. What was your family like?

A: “My father grew up very poor in a small town in Michoacán in the southwest part of Mexico. In Mexico City, he had a tiny grocery store in an old-fashioned market, and we were lower middle class.

One of the things I learned was to work hard. There’s nobody I know who worked as hard as my father. He opened his store every day of the year, [Mexican] Independence Day or New Year’s or Christmas. He worked hard so we could have a better life than he did.

We learned English from a very young age. My elementary school was called Westminster School because he wanted a school where we would learn English.

As for my mother, she stayed with us [at home] and made sure we did our homework and were taken care of. I learned about being honest and dedicating to what you were doing.”

Q: You trained at the Salvador Zubirán National Institute of Health Sciences and Nutrition in Mexico City. Then what happened? 

A: “Through encouragement by my dermatologist older brother and a mentor at the institution where I was training as a hematologist, I decided to come to the United States.

My initial focus was going to be on coagulation and thrombosis. I came to Houston (Texas) for a fellowship at the University of Texas Health Science Center.

Then I started doing my rotation for the malignant part of the fellowship at MD Anderson Cancer Center [Houston]. One of my first rotations was with Susan M. O’Brien, [MD,] who became my greatest mentor throughout my career. I really enjoyed my rotation. I thought she was great clinically, and she was doing research and teaching. That’s what I wanted for my career.”

Q: What drew you to leukemia specifically?

A: “Dr O’Brien worked in leukemia during my initial rotation, and I really loved it. It was hard work, but it was very inspiring to see the clinical research and the things you could for patients. She had a lot of joy doing that. 

I told my program director I’d change and transfer to MD Anderson, and I ended up staying at MD Anderson for 23 years.”

Q: What was leukemia research like in those days?

A: “We didn’t have the understanding of the biology and the new drugs that we have now. When I started in Mexico, we didn’t even have hydroxyurea. What we were doing was much more basic. But still, the field sounded like a great field to be involved with because they were doing so many trials and had an outstanding database. 

Because of the influence of Dr [Moshe] Talpaz, [MD,] I started getting very involved with CML. In my initial years as a young faculty, I started working with him on interferon. Then imatinib appeared. I saw even from the phase 1 study how impressive the outcomes were in patients who had no response to anything and were in bad shape.”

Q: What CML medications have you worked on?

A: “I’ve been involved with all of them. Imatinib early on, then I led trials with dasatinib and nilotinib. Then, I led the registration trials of bosutinib and ponatinib. More recently, I was part of the development of asciminib.”

Q: What were some of the biggest challenges in CML research?

A: “We had an opportunity to do a lot of analysis about TKIs [tyrosine kinase inhibitors] when these were new drugs. It was a very steep curve of learning, how to monitor and manage side effects.

Then patients were starting to have resistance to two to three TKIs. Ponatinib came along, and it was an incredibly effective drug. But after it was approved, we started to recognize the occurrence of heart attacks and strokes.

That was unexpected and not something that was known for any TKI. It was a big challenge. The drug was taken off the market for some time, and trials were put on hold by the FDA [US Food and Drug Administration].

We scrambled to understand the mechanism of action. For a year or two, it was a stressful time. But eventually we moved past it, and we learned a lot.”

Q: What sort of work have you done in Latin America?

A: “I’ve always been very close to Latin America. I have many good friends and colleagues there, and I’ve always been interested in working with them. 

We’ve done research and studies and created an organization called Latin American Leukemia Net to develop more trials in Latin America. The most rewarding thing has been the educational programs for patients that we’ve done, helping them understand the disease, the treatments, and the goals of treatment. 

We’ve conducted a number of programs, and they have been effective, well-attended, and well received. I still work with my colleagues to develop local guidelines and do collaborative research.”

Q: What convinced you to leave MD Anderson for Georgia?

A: “I never thought I’d leave MD Anderson. I had my well-oiled machine of clinical trials, my clinic, and my fellowship program. But the one thing that I wanted to see if I could try next was to develop an institution.

That was the goal here, to take the Georgia Cancer Center to NCI [National Cancer Institute] designation. So, I thought, ‘That’s a nice challenge.’ It may be a good opportunity to try a different aspect of what it means to be an oncologist.

There are days that you think, ‘What am I doing here?’ when you have to deal with budgets and personnel and all these things. But it’s part of the process. It’s still good to know that we have a goal, and that we’re going to make it. 

Also, I still see my patients, and I enjoy that I still do some research and mentoring.”

Q: What’s the current state of CML treatment?

A: “Many patients have a pretty much normal life expectancy while [on therapy]. Still, one of the goals of many patients is to stop therapy. But that’s a reality only for a small percentage of patients. How can we make that happen for more patients?”

Q: By stopping therapy, do you mean curing the cancer?

A: “Yes, pretty much. You have a good response, you stop the therapy, and it doesn’t come back.

There are also patients who really don’t do well. We hear about CML being with a disease with such a good outcome, but we have patients for whom nothing works. Is it a matter of [needing] another TKI, or do we need to look at something else?”

Q: What do you see on the horizon?

A: “We are developing new approaches like combination therapies. We’re scratching the surface on that. We need to understand which combinations work, and where and when.

And we can make more efficient uses of the drugs we have now in terms of which ones to use when, the doses, the safety profiles. I think we can do better.”

Cortes disclosed consulting for Amphivena, Astellas, Bio-Path, BioLineRx, Bristol Myers Squibb, Daiichi Sankyo, Jazz, Novartis, Pfizer, and Takeda and research funding from Astellas Pharma, Bristol Myers Squibb, Daiichi Sankyo, Immunogen, Jazz, Merus, Novartis, Pfizer, Sun Pharma, Takeda, Tolero and Trovagene.
 

A version of this article appeared on Medscape.com.

If the name of leukemia specialist Jorge Cortes, MD, appears any more often in PubMed, they’ll need to name a wing after him. 

Over 30 years, Cortes has led or coauthored hundreds of studies, including many trials of landmark drugs to treat chronic myeloid leukemia (CML). His work has helped transform CML into an often-survivable disease instead of one that took the lives of most patients within 5 years.

“It’s been remarkable to see the evolution in CML and to be part of that transition as a fellow, as faculty, and as leader of some of the trials,” said Cortes, who directs the Georgia Cancer Center at Augusta University. “I’m the luckiest person in the world.”

In an interview, Cortes talked about his youth in Mexico, his research path, and his close connections to cancer medicine in Latin America.

Q: You grew up in Mexico City. What was your family like?

A: “My father grew up very poor in a small town in Michoacán in the southwest part of Mexico. In Mexico City, he had a tiny grocery store in an old-fashioned market, and we were lower middle class.

One of the things I learned was to work hard. There’s nobody I know who worked as hard as my father. He opened his store every day of the year, [Mexican] Independence Day or New Year’s or Christmas. He worked hard so we could have a better life than he did.

We learned English from a very young age. My elementary school was called Westminster School because he wanted a school where we would learn English.

As for my mother, she stayed with us [at home] and made sure we did our homework and were taken care of. I learned about being honest and dedicating to what you were doing.”

Q: You trained at the Salvador Zubirán National Institute of Health Sciences and Nutrition in Mexico City. Then what happened? 

A: “Through encouragement by my dermatologist older brother and a mentor at the institution where I was training as a hematologist, I decided to come to the United States.

My initial focus was going to be on coagulation and thrombosis. I came to Houston (Texas) for a fellowship at the University of Texas Health Science Center.

Then I started doing my rotation for the malignant part of the fellowship at MD Anderson Cancer Center [Houston]. One of my first rotations was with Susan M. O’Brien, [MD,] who became my greatest mentor throughout my career. I really enjoyed my rotation. I thought she was great clinically, and she was doing research and teaching. That’s what I wanted for my career.”

Q: What drew you to leukemia specifically?

A: “Dr O’Brien worked in leukemia during my initial rotation, and I really loved it. It was hard work, but it was very inspiring to see the clinical research and the things you could for patients. She had a lot of joy doing that. 

I told my program director I’d change and transfer to MD Anderson, and I ended up staying at MD Anderson for 23 years.”

Q: What was leukemia research like in those days?

A: “We didn’t have the understanding of the biology and the new drugs that we have now. When I started in Mexico, we didn’t even have hydroxyurea. What we were doing was much more basic. But still, the field sounded like a great field to be involved with because they were doing so many trials and had an outstanding database. 

Because of the influence of Dr [Moshe] Talpaz, [MD,] I started getting very involved with CML. In my initial years as a young faculty, I started working with him on interferon. Then imatinib appeared. I saw even from the phase 1 study how impressive the outcomes were in patients who had no response to anything and were in bad shape.”

Q: What CML medications have you worked on?

A: “I’ve been involved with all of them. Imatinib early on, then I led trials with dasatinib and nilotinib. Then, I led the registration trials of bosutinib and ponatinib. More recently, I was part of the development of asciminib.”

Q: What were some of the biggest challenges in CML research?

A: “We had an opportunity to do a lot of analysis about TKIs [tyrosine kinase inhibitors] when these were new drugs. It was a very steep curve of learning, how to monitor and manage side effects.

Then patients were starting to have resistance to two to three TKIs. Ponatinib came along, and it was an incredibly effective drug. But after it was approved, we started to recognize the occurrence of heart attacks and strokes.

That was unexpected and not something that was known for any TKI. It was a big challenge. The drug was taken off the market for some time, and trials were put on hold by the FDA [US Food and Drug Administration].

We scrambled to understand the mechanism of action. For a year or two, it was a stressful time. But eventually we moved past it, and we learned a lot.”

Q: What sort of work have you done in Latin America?

A: “I’ve always been very close to Latin America. I have many good friends and colleagues there, and I’ve always been interested in working with them. 

We’ve done research and studies and created an organization called Latin American Leukemia Net to develop more trials in Latin America. The most rewarding thing has been the educational programs for patients that we’ve done, helping them understand the disease, the treatments, and the goals of treatment. 

We’ve conducted a number of programs, and they have been effective, well-attended, and well received. I still work with my colleagues to develop local guidelines and do collaborative research.”

Q: What convinced you to leave MD Anderson for Georgia?

A: “I never thought I’d leave MD Anderson. I had my well-oiled machine of clinical trials, my clinic, and my fellowship program. But the one thing that I wanted to see if I could try next was to develop an institution.

That was the goal here, to take the Georgia Cancer Center to NCI [National Cancer Institute] designation. So, I thought, ‘That’s a nice challenge.’ It may be a good opportunity to try a different aspect of what it means to be an oncologist.

There are days that you think, ‘What am I doing here?’ when you have to deal with budgets and personnel and all these things. But it’s part of the process. It’s still good to know that we have a goal, and that we’re going to make it. 

Also, I still see my patients, and I enjoy that I still do some research and mentoring.”

Q: What’s the current state of CML treatment?

A: “Many patients have a pretty much normal life expectancy while [on therapy]. Still, one of the goals of many patients is to stop therapy. But that’s a reality only for a small percentage of patients. How can we make that happen for more patients?”

Q: By stopping therapy, do you mean curing the cancer?

A: “Yes, pretty much. You have a good response, you stop the therapy, and it doesn’t come back.

There are also patients who really don’t do well. We hear about CML being with a disease with such a good outcome, but we have patients for whom nothing works. Is it a matter of [needing] another TKI, or do we need to look at something else?”

Q: What do you see on the horizon?

A: “We are developing new approaches like combination therapies. We’re scratching the surface on that. We need to understand which combinations work, and where and when.

And we can make more efficient uses of the drugs we have now in terms of which ones to use when, the doses, the safety profiles. I think we can do better.”

Cortes disclosed consulting for Amphivena, Astellas, Bio-Path, BioLineRx, Bristol Myers Squibb, Daiichi Sankyo, Jazz, Novartis, Pfizer, and Takeda and research funding from Astellas Pharma, Bristol Myers Squibb, Daiichi Sankyo, Immunogen, Jazz, Merus, Novartis, Pfizer, Sun Pharma, Takeda, Tolero and Trovagene.
 

A version of this article appeared on Medscape.com.

WASHINGTON — Colchicine does not protect against major cardiovascular adverse events after an acute myocardial infarction, according to a multinational placebo-controlled trial of more than 7000 patients.

The CLEAR SYNERGY (OASIS 9) study, called “the largest trial ever of colchicine in acute MI,” showed no hint of benefit in an adverse event curve for colchicine relative to placebo over 5 years, which suggests that the role of this drug after myocardial infarction (MI) “is uncertain,” Sanjit Jolly, MD, an interventional cardiologist at Hamilton Health Sciences and a professor of medicine at McMaster University in Hamilton, Ontario, Canada, reported at Transcatheter Cardiovascular Therapeutics (TCT) 2024.

For the primary composite outcome — cardiovascular death, MI, stroke, and ischemia-driven revascularization — the event curves in the colchicine and placebo groups remained essentially superimposed over 5 years of follow-up, with only a slight separation after 4 years. The hazard ratio for the primary endpoint showed a 1% difference in favor of colchicine (hazard ratio [HR], 0.99; P = .93).

There were no meaningful differences in any of the individual endpoint components; all 95% CIs straddled the line of unity. Rates of cardiovascular death (3.3% vs 3.2%) and stroke (1.4% vs 1.2%) were numerically higher in the colchicine group than in the placebo group. Rates of MI (2.9% vs 3.1%) and ischemia-driven revascularization (4.6% vs 4.7%) were numerically lower in the colchicine group.

 

No Difference

No adverse outcomes, including all-cause death (4.6% vs 5.1%), approached significance, with the exception of noncardiovascular death (13.0% vs 1.9%). For this outcome, the 95% CI stopped just short of the line of unity (HR, 0.68; 95% CI, 0.46-0.99).

Rates of adverse events (31.9% vs 31.7%; P = .86), serious adverse events (6.7% vs 7.4%; P = .22), and serious infections (2.5% vs 2.9%; P = .85) were similar in the colchicine and placebo groups, but diarrhea, a known side effect of colchicine, was higher in the colchicine group (10.2% vs 6.6%; P < .001).

Given these results, a panelist questioned the use of the word “uncertain” to describe the findings during the late-breaker session in which these results were presented.

“I think you are selling yourself short,” said J. Dawn Abbott, MD, director of the Interventional Cardiology Fellowship Training Program at the Lifespan Cardiovascular Institute, Brown University in Providence, Rhode Island. Based on the size and conduct of this trial, she called the results “definitive” and suggested that the guidelines should be adjusted.

 

The OASIS 9 Trial

In OASIS 9, 3528 patients were randomized to colchicine, and 3534 were randomized to placebo. A second randomization in both groups was to spironolactone or placebo; these results will be presented at the upcoming American Heart Association (AHA) 2024 meeting. Both analyses will be published in The New England Journal of Medicine at that time, Jolly reported.

The study involved 104 sites in Australia, Egypt, Europe, Nepal, and North America. Follow-up in both groups exceeded 99%. Most patients had an ST-elevation MI (STEMI), but about 5% of those enrolled had a non-STEMI. Less than 10% of patients had experienced a previous MI.

Less than 5% of patients were discharged on sodium-glucose cotransporter 2 therapy, and more than 95% were discharged on aspirin and a statin. Nearly 80% were discharged on an angiotensin-converting enzyme inhibitor, and most patients received an anticoagulant. More than 95% of patients were implanted with a drug-eluting stent.

At month 3, C-reactive protein levels were significantly lower in the colchicine group than in the placebo group. C-reactive protein is a biomarker for the anti-inflammatory effect that is considered to be colchicine’s primary mechanism of action. An anti-inflammatory effect has been cited as the probable explanation for the positive results shown in the COLCOT and LODOCO2 trials, published in 2019 and 2020, respectively.

In COLCOT, which randomized 4745 patients who experienced an acute MI in the previous 30 days, colchicine was associated with a 23% reduction in a composite major cardiovascular adverse events endpoint relative to placebo (HR, 0.77; P = .02). In LODOCO2, which randomized 5522 patients with chronic coronary disease, colchicine was associated with a 31% reduction in an adverse event composite endpoint (HR, 0.68; P < .0001).

However, two more recent trials — CONVINCE and CHANCE-3 — showed no difference between colchicine and placebo for the endpoint of recurrent stroke at 90 days. CONVINCE, with approximately 3000 patients, was relatively small, whereas CHANCE-3 randomized more than 8000 patients and showed no effect on the risk for stroke (HR, 0.98; 95% CI, 0.83-1.16).

 

New Data Challenge Guidelines

Of these trials, COLCOT was the most similar to OASIS 9, according to Jolly. Among the differences, OASIS 9 was initiated earlier and was larger than the other trials, so it had more power to address the study question.

Given the absence of benefit, Jolly indicated that OASIS 9 might disrupt both the joint American College of Cardiology and AHA guidelines, which gave colchicine a class 2b recommendation in 2023, and the European Society of Cardiology guidelines, which gave colchicine a 2a recommendation.

“This is a big deal for me,” said Ajay J. Kirtane, director of the Interventional Cardiovascular Care program at Columbia University in New York City. As someone who is now using colchicine routinely, these data have changed his opinion.

The previous data supporting the use of colchicine “were just so-so,” he explained. “Now I have a good rationale” for foregoing the routine use of this therapy.

Jolly said that he had put his own father on colchicine after an acute MI on the basis of the guidelines, but immediately took him off this therapy when the data from OASIS 9 were unblinded.

“The only signal from this trial was an increased risk of diarrhea,” Jolly said. The results, at the very least, suggest that colchicine “is not for everyone” after an acute MI, although he emphasized that these results do not rule out the potential for benefit from anti-inflammatory therapy. Ongoing trials, including one targeting interleukin 6, a cytokine associated with inflammation, remain of interest, he added.

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

WASHINGTON — Colchicine does not protect against major cardiovascular adverse events after an acute myocardial infarction, according to a multinational placebo-controlled trial of more than 7000 patients.

The CLEAR SYNERGY (OASIS 9) study, called “the largest trial ever of colchicine in acute MI,” showed no hint of benefit in an adverse event curve for colchicine relative to placebo over 5 years, which suggests that the role of this drug after myocardial infarction (MI) “is uncertain,” Sanjit Jolly, MD, an interventional cardiologist at Hamilton Health Sciences and a professor of medicine at McMaster University in Hamilton, Ontario, Canada, reported at Transcatheter Cardiovascular Therapeutics (TCT) 2024.

For the primary composite outcome — cardiovascular death, MI, stroke, and ischemia-driven revascularization — the event curves in the colchicine and placebo groups remained essentially superimposed over 5 years of follow-up, with only a slight separation after 4 years. The hazard ratio for the primary endpoint showed a 1% difference in favor of colchicine (hazard ratio [HR], 0.99; P = .93).

There were no meaningful differences in any of the individual endpoint components; all 95% CIs straddled the line of unity. Rates of cardiovascular death (3.3% vs 3.2%) and stroke (1.4% vs 1.2%) were numerically higher in the colchicine group than in the placebo group. Rates of MI (2.9% vs 3.1%) and ischemia-driven revascularization (4.6% vs 4.7%) were numerically lower in the colchicine group.

 

No Difference

No adverse outcomes, including all-cause death (4.6% vs 5.1%), approached significance, with the exception of noncardiovascular death (13.0% vs 1.9%). For this outcome, the 95% CI stopped just short of the line of unity (HR, 0.68; 95% CI, 0.46-0.99).

Rates of adverse events (31.9% vs 31.7%; P = .86), serious adverse events (6.7% vs 7.4%; P = .22), and serious infections (2.5% vs 2.9%; P = .85) were similar in the colchicine and placebo groups, but diarrhea, a known side effect of colchicine, was higher in the colchicine group (10.2% vs 6.6%; P < .001).

Given these results, a panelist questioned the use of the word “uncertain” to describe the findings during the late-breaker session in which these results were presented.

“I think you are selling yourself short,” said J. Dawn Abbott, MD, director of the Interventional Cardiology Fellowship Training Program at the Lifespan Cardiovascular Institute, Brown University in Providence, Rhode Island. Based on the size and conduct of this trial, she called the results “definitive” and suggested that the guidelines should be adjusted.

 

The OASIS 9 Trial

In OASIS 9, 3528 patients were randomized to colchicine, and 3534 were randomized to placebo. A second randomization in both groups was to spironolactone or placebo; these results will be presented at the upcoming American Heart Association (AHA) 2024 meeting. Both analyses will be published in The New England Journal of Medicine at that time, Jolly reported.

The study involved 104 sites in Australia, Egypt, Europe, Nepal, and North America. Follow-up in both groups exceeded 99%. Most patients had an ST-elevation MI (STEMI), but about 5% of those enrolled had a non-STEMI. Less than 10% of patients had experienced a previous MI.

Less than 5% of patients were discharged on sodium-glucose cotransporter 2 therapy, and more than 95% were discharged on aspirin and a statin. Nearly 80% were discharged on an angiotensin-converting enzyme inhibitor, and most patients received an anticoagulant. More than 95% of patients were implanted with a drug-eluting stent.

At month 3, C-reactive protein levels were significantly lower in the colchicine group than in the placebo group. C-reactive protein is a biomarker for the anti-inflammatory effect that is considered to be colchicine’s primary mechanism of action. An anti-inflammatory effect has been cited as the probable explanation for the positive results shown in the COLCOT and LODOCO2 trials, published in 2019 and 2020, respectively.

In COLCOT, which randomized 4745 patients who experienced an acute MI in the previous 30 days, colchicine was associated with a 23% reduction in a composite major cardiovascular adverse events endpoint relative to placebo (HR, 0.77; P = .02). In LODOCO2, which randomized 5522 patients with chronic coronary disease, colchicine was associated with a 31% reduction in an adverse event composite endpoint (HR, 0.68; P < .0001).

However, two more recent trials — CONVINCE and CHANCE-3 — showed no difference between colchicine and placebo for the endpoint of recurrent stroke at 90 days. CONVINCE, with approximately 3000 patients, was relatively small, whereas CHANCE-3 randomized more than 8000 patients and showed no effect on the risk for stroke (HR, 0.98; 95% CI, 0.83-1.16).

 

New Data Challenge Guidelines

Of these trials, COLCOT was the most similar to OASIS 9, according to Jolly. Among the differences, OASIS 9 was initiated earlier and was larger than the other trials, so it had more power to address the study question.

Given the absence of benefit, Jolly indicated that OASIS 9 might disrupt both the joint American College of Cardiology and AHA guidelines, which gave colchicine a class 2b recommendation in 2023, and the European Society of Cardiology guidelines, which gave colchicine a 2a recommendation.

“This is a big deal for me,” said Ajay J. Kirtane, director of the Interventional Cardiovascular Care program at Columbia University in New York City. As someone who is now using colchicine routinely, these data have changed his opinion.

The previous data supporting the use of colchicine “were just so-so,” he explained. “Now I have a good rationale” for foregoing the routine use of this therapy.

Jolly said that he had put his own father on colchicine after an acute MI on the basis of the guidelines, but immediately took him off this therapy when the data from OASIS 9 were unblinded.

“The only signal from this trial was an increased risk of diarrhea,” Jolly said. The results, at the very least, suggest that colchicine “is not for everyone” after an acute MI, although he emphasized that these results do not rule out the potential for benefit from anti-inflammatory therapy. Ongoing trials, including one targeting interleukin 6, a cytokine associated with inflammation, remain of interest, he added.

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

WASHINGTON — Colchicine does not protect against major cardiovascular adverse events after an acute myocardial infarction, according to a multinational placebo-controlled trial of more than 7000 patients.

The CLEAR SYNERGY (OASIS 9) study, called “the largest trial ever of colchicine in acute MI,” showed no hint of benefit in an adverse event curve for colchicine relative to placebo over 5 years, which suggests that the role of this drug after myocardial infarction (MI) “is uncertain,” Sanjit Jolly, MD, an interventional cardiologist at Hamilton Health Sciences and a professor of medicine at McMaster University in Hamilton, Ontario, Canada, reported at Transcatheter Cardiovascular Therapeutics (TCT) 2024.

For the primary composite outcome — cardiovascular death, MI, stroke, and ischemia-driven revascularization — the event curves in the colchicine and placebo groups remained essentially superimposed over 5 years of follow-up, with only a slight separation after 4 years. The hazard ratio for the primary endpoint showed a 1% difference in favor of colchicine (hazard ratio [HR], 0.99; P = .93).

There were no meaningful differences in any of the individual endpoint components; all 95% CIs straddled the line of unity. Rates of cardiovascular death (3.3% vs 3.2%) and stroke (1.4% vs 1.2%) were numerically higher in the colchicine group than in the placebo group. Rates of MI (2.9% vs 3.1%) and ischemia-driven revascularization (4.6% vs 4.7%) were numerically lower in the colchicine group.

 

No Difference

No adverse outcomes, including all-cause death (4.6% vs 5.1%), approached significance, with the exception of noncardiovascular death (13.0% vs 1.9%). For this outcome, the 95% CI stopped just short of the line of unity (HR, 0.68; 95% CI, 0.46-0.99).

Rates of adverse events (31.9% vs 31.7%; P = .86), serious adverse events (6.7% vs 7.4%; P = .22), and serious infections (2.5% vs 2.9%; P = .85) were similar in the colchicine and placebo groups, but diarrhea, a known side effect of colchicine, was higher in the colchicine group (10.2% vs 6.6%; P < .001).

Given these results, a panelist questioned the use of the word “uncertain” to describe the findings during the late-breaker session in which these results were presented.

“I think you are selling yourself short,” said J. Dawn Abbott, MD, director of the Interventional Cardiology Fellowship Training Program at the Lifespan Cardiovascular Institute, Brown University in Providence, Rhode Island. Based on the size and conduct of this trial, she called the results “definitive” and suggested that the guidelines should be adjusted.

 

The OASIS 9 Trial

In OASIS 9, 3528 patients were randomized to colchicine, and 3534 were randomized to placebo. A second randomization in both groups was to spironolactone or placebo; these results will be presented at the upcoming American Heart Association (AHA) 2024 meeting. Both analyses will be published in The New England Journal of Medicine at that time, Jolly reported.

The study involved 104 sites in Australia, Egypt, Europe, Nepal, and North America. Follow-up in both groups exceeded 99%. Most patients had an ST-elevation MI (STEMI), but about 5% of those enrolled had a non-STEMI. Less than 10% of patients had experienced a previous MI.

Less than 5% of patients were discharged on sodium-glucose cotransporter 2 therapy, and more than 95% were discharged on aspirin and a statin. Nearly 80% were discharged on an angiotensin-converting enzyme inhibitor, and most patients received an anticoagulant. More than 95% of patients were implanted with a drug-eluting stent.

At month 3, C-reactive protein levels were significantly lower in the colchicine group than in the placebo group. C-reactive protein is a biomarker for the anti-inflammatory effect that is considered to be colchicine’s primary mechanism of action. An anti-inflammatory effect has been cited as the probable explanation for the positive results shown in the COLCOT and LODOCO2 trials, published in 2019 and 2020, respectively.

In COLCOT, which randomized 4745 patients who experienced an acute MI in the previous 30 days, colchicine was associated with a 23% reduction in a composite major cardiovascular adverse events endpoint relative to placebo (HR, 0.77; P = .02). In LODOCO2, which randomized 5522 patients with chronic coronary disease, colchicine was associated with a 31% reduction in an adverse event composite endpoint (HR, 0.68; P < .0001).

However, two more recent trials — CONVINCE and CHANCE-3 — showed no difference between colchicine and placebo for the endpoint of recurrent stroke at 90 days. CONVINCE, with approximately 3000 patients, was relatively small, whereas CHANCE-3 randomized more than 8000 patients and showed no effect on the risk for stroke (HR, 0.98; 95% CI, 0.83-1.16).

 

New Data Challenge Guidelines

Of these trials, COLCOT was the most similar to OASIS 9, according to Jolly. Among the differences, OASIS 9 was initiated earlier and was larger than the other trials, so it had more power to address the study question.

Given the absence of benefit, Jolly indicated that OASIS 9 might disrupt both the joint American College of Cardiology and AHA guidelines, which gave colchicine a class 2b recommendation in 2023, and the European Society of Cardiology guidelines, which gave colchicine a 2a recommendation.

“This is a big deal for me,” said Ajay J. Kirtane, director of the Interventional Cardiovascular Care program at Columbia University in New York City. As someone who is now using colchicine routinely, these data have changed his opinion.

The previous data supporting the use of colchicine “were just so-so,” he explained. “Now I have a good rationale” for foregoing the routine use of this therapy.

Jolly said that he had put his own father on colchicine after an acute MI on the basis of the guidelines, but immediately took him off this therapy when the data from OASIS 9 were unblinded.

“The only signal from this trial was an increased risk of diarrhea,” Jolly said. The results, at the very least, suggest that colchicine “is not for everyone” after an acute MI, although he emphasized that these results do not rule out the potential for benefit from anti-inflammatory therapy. Ongoing trials, including one targeting interleukin 6, a cytokine associated with inflammation, remain of interest, he added.

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

TOPLINE:

Antibiotic use during influenza infection increases lung eosinophils, impairing immunity against secondary bacterial pneumonia. This study highlights the detrimental effects of antibiotics on lung health during viral infections.

METHODOLOGY:

• Researchers conducted a murine model study to evaluate the impact of antibiotic use during influenza infection on lung immunity. Mice were treated with a broad-spectrum antibiotic cocktail (vancomycin, neomycin, ampicillin, and metronidazole) starting 7 days before influenza infection.
• The study included intranasal infection with influenza virus followed by a secondary challenge with methicillin-resistant Staphylococcus aureus (MRSA).
• Lung eosinophils, macrophage function, and MRSA clearance were assessed through various immunologic and histologic analyses.
• Finally, in sub-study, a total of three cohorts of hospitalized patients were evaluated to correlate eosinophil levels with antibiotic use, systemic inflammation, and outcomes.

TAKEAWAY:

• Antibiotic use during influenza infection impairs lung immunity, leading to increased lung eosinophils and reduced macrophage function.
• The study found that antibiotic treatment during influenza infection caused fungal dysbiosis, driving lung eosinophilia and impairing MRSA clearance.
• The detrimental effects of antibiotics on lung immunity were specific to the two-hit model of influenza followed by MRSA infection in mice.
• In hospitalized patients, eosinophil levels positively correlated with antibiotic use, systemic inflammation, and worsened outcomes.

IN PRACTICE:

“Our study highlights the pernicious effects of antibiotic use during viral infections and defines a mechanism whereby antibiotics perturb the gut mycobiome and result in lung eosinophilia. In turn, lung eosinophils, via release of MBP-1, suppress alveolar macrophage clearance of bacteria,” the authors of the study wrote.

SOURCE:

This study was led by Marilia Sanches Santos Rizzo Zuttion, Cedars-Sinai Medical Center in Los Angeles. It was published online in The Journal of Clinical Investigation.

LIMITATIONS:

This study’s limitations included the use of a murine model, which may not fully replicate human immune responses. Additionally, the study focused on a specific antibiotic cocktail, and results may vary with different antibiotics. The findings were also specific to the two-hit model of influenza followed by MRSA infection, limiting generalizability to other infections.

DISCLOSURES:

This study was supported by grants from the National Institutes of Health. Marilia Sanches Santos Rizzo Zuttion received research funding from Pfizer Inc. Additional disclosures are noted in the original article.

 

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:

Antibiotic use during influenza infection increases lung eosinophils, impairing immunity against secondary bacterial pneumonia. This study highlights the detrimental effects of antibiotics on lung health during viral infections.

METHODOLOGY:

• Researchers conducted a murine model study to evaluate the impact of antibiotic use during influenza infection on lung immunity. Mice were treated with a broad-spectrum antibiotic cocktail (vancomycin, neomycin, ampicillin, and metronidazole) starting 7 days before influenza infection.
• The study included intranasal infection with influenza virus followed by a secondary challenge with methicillin-resistant Staphylococcus aureus (MRSA).
• Lung eosinophils, macrophage function, and MRSA clearance were assessed through various immunologic and histologic analyses.
• Finally, in sub-study, a total of three cohorts of hospitalized patients were evaluated to correlate eosinophil levels with antibiotic use, systemic inflammation, and outcomes.

TAKEAWAY:

• Antibiotic use during influenza infection impairs lung immunity, leading to increased lung eosinophils and reduced macrophage function.
• The study found that antibiotic treatment during influenza infection caused fungal dysbiosis, driving lung eosinophilia and impairing MRSA clearance.
• The detrimental effects of antibiotics on lung immunity were specific to the two-hit model of influenza followed by MRSA infection in mice.
• In hospitalized patients, eosinophil levels positively correlated with antibiotic use, systemic inflammation, and worsened outcomes.

IN PRACTICE:

“Our study highlights the pernicious effects of antibiotic use during viral infections and defines a mechanism whereby antibiotics perturb the gut mycobiome and result in lung eosinophilia. In turn, lung eosinophils, via release of MBP-1, suppress alveolar macrophage clearance of bacteria,” the authors of the study wrote.

SOURCE:

This study was led by Marilia Sanches Santos Rizzo Zuttion, Cedars-Sinai Medical Center in Los Angeles. It was published online in The Journal of Clinical Investigation.

LIMITATIONS:

This study’s limitations included the use of a murine model, which may not fully replicate human immune responses. Additionally, the study focused on a specific antibiotic cocktail, and results may vary with different antibiotics. The findings were also specific to the two-hit model of influenza followed by MRSA infection, limiting generalizability to other infections.

DISCLOSURES:

This study was supported by grants from the National Institutes of Health. Marilia Sanches Santos Rizzo Zuttion received research funding from Pfizer Inc. Additional disclosures are noted in the original article.

 

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:

Antibiotic use during influenza infection increases lung eosinophils, impairing immunity against secondary bacterial pneumonia. This study highlights the detrimental effects of antibiotics on lung health during viral infections.

METHODOLOGY:

• Researchers conducted a murine model study to evaluate the impact of antibiotic use during influenza infection on lung immunity. Mice were treated with a broad-spectrum antibiotic cocktail (vancomycin, neomycin, ampicillin, and metronidazole) starting 7 days before influenza infection.
• The study included intranasal infection with influenza virus followed by a secondary challenge with methicillin-resistant Staphylococcus aureus (MRSA).
• Lung eosinophils, macrophage function, and MRSA clearance were assessed through various immunologic and histologic analyses.
• Finally, in sub-study, a total of three cohorts of hospitalized patients were evaluated to correlate eosinophil levels with antibiotic use, systemic inflammation, and outcomes.

TAKEAWAY:

• Antibiotic use during influenza infection impairs lung immunity, leading to increased lung eosinophils and reduced macrophage function.
• The study found that antibiotic treatment during influenza infection caused fungal dysbiosis, driving lung eosinophilia and impairing MRSA clearance.
• The detrimental effects of antibiotics on lung immunity were specific to the two-hit model of influenza followed by MRSA infection in mice.
• In hospitalized patients, eosinophil levels positively correlated with antibiotic use, systemic inflammation, and worsened outcomes.

IN PRACTICE:

“Our study highlights the pernicious effects of antibiotic use during viral infections and defines a mechanism whereby antibiotics perturb the gut mycobiome and result in lung eosinophilia. In turn, lung eosinophils, via release of MBP-1, suppress alveolar macrophage clearance of bacteria,” the authors of the study wrote.

SOURCE:

This study was led by Marilia Sanches Santos Rizzo Zuttion, Cedars-Sinai Medical Center in Los Angeles. It was published online in The Journal of Clinical Investigation.

LIMITATIONS:

This study’s limitations included the use of a murine model, which may not fully replicate human immune responses. Additionally, the study focused on a specific antibiotic cocktail, and results may vary with different antibiotics. The findings were also specific to the two-hit model of influenza followed by MRSA infection, limiting generalizability to other infections.

DISCLOSURES:

This study was supported by grants from the National Institutes of Health. Marilia Sanches Santos Rizzo Zuttion received research funding from Pfizer Inc. Additional disclosures are noted in the original article.

 

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.