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Diabetes drug tied to lower dementia risk
new research suggests.
Overall, in a large cohort study from South Korea, patients who took pioglitazone were 16% less likely to develop dementia over an average of 10 years than peers who did not take the drug.
However, the dementia risk reduction was 54% among those with ischemic heart disease and 43% among those with a history of stroke.
“Our study was to see the association between pioglitazone use and incidence of dementia, not how (with what mechanisms) this drug can suppress dementia pathology,” coinvestigator Eosu Kim, MD, PhD, Yonsei University, Seoul, South Korea, said in an interview.
However, “as we found this drug is more effective in diabetic patients who have blood circulation problems in the heart or brain than in those without such problems, we speculate that pioglitazone’s antidementia action may be related to improving blood vessel’s health,” Dr. Kim said.
This finding suggests that pioglitazone could be used as a personalized treatment approach for dementia prevention in this subgroup of patients with diabetes, the researchers noted.
The results were published online in Neurology.
Dose-response relationship
Risk for dementia is doubled in adults with T2DM, the investigators wrote. Prior studies have suggested that pioglitazone may protect against dementia, as well as a first or recurrent stroke, in patients with T2DM.
This led Dr. Kim and colleagues to examine the effects of pioglitazone on dementia risk overall and in relation to stroke and ischemic heart disease.
Using the national Korean health database, the researchers identified 91,218 adults aged 50 and older with new-onset T2DM who did not have dementia. A total of 3,467 were treated with pioglitazone.
Pioglitazone exposure was defined as a total cumulative daily dose of 90 or more calculated from all dispensations during 4 years after T2DM diagnosis, with outcomes assessed after this period.
Over an average of 10 years, 8.3% of pioglitazone users developed dementia, compared with 10.0% of nonusers.
There was a statistically significant 16% lower risk for developing all-cause dementia among pioglitazone users than among nonusers (adjusted hazard ratio, 0.84; 95% confidence interval, 0.75-0.95).
A dose-response relationship was evident; pioglitazone users who received the highest cumulative daily dose were at lower risk for dementia (aHR, 0.72; 95% CI, 0.55-0.94).
Several limitations
The reduced risk for dementia was more pronounced among patients who used pioglitazone for 4 years in comparison with patients who did not use the drug (aHR, 0.63; 95% CI, 0.44-0.90).
The apparent protective effect of pioglitazone with regard to dementia was greater among those with a history of ischemic heart disease (aHR, 0.46; 95% CI, 0.24-0.90) or stroke (aHR, 0.57; 95% CI, 0.38-0.86) before diabetes diagnosis.
The incidence of stroke was also reduced with pioglitazone use (aHR, 0.81; 95% CI, 0.66-1.0).
“These results provide valuable information on who could potentially benefit from pioglitazone use for prevention of dementia,” Dr. Kim said in a news release.
However, “the risk and benefit balance of long-term use of this drug to prevent dementia should be prospectively assessed,” he said in an interview.
The researchers cautioned that the study was observational; hence, the reported associations cannot address causal relationships. Also, because of the use of claims data, drug compliance could not be guaranteed, and exposure may have been overestimated.
There is also the potential for selection bias, and no information on apolipoprotein E was available, they noted.
More data needed
In an accompanying editorial, Colleen J. Maxwell, PhD, University of Waterloo (Ont.), and colleagues wrote that the results “not only support previous studies showing the potential cognitive benefit of pioglitazone but also extend our understanding of this benefit through the mediating effect of reducing ischemic stroke.”
However, because of their associated risks, which include fractures, weight gain, heart failure, and bladder cancer, thiazolidinediones are not currently favored in diabetes management guidelines – and their use has significantly declined since the mid to late 2000s, the editorialists noted.
They agreed that it will be important to reassess the risk-benefit profile of pioglitazone in T2DM as additional findings emerge.
They also noted that sodium-glucose cotransporter-2 inhibitors, which have significant cardiovascular and renal benefits and minimal side effects, may also lower the risk for dementia.
“As both pioglitazone and SGLT-2 inhibitors are second-line options for physicians, the current decision would easily be in favor of SGLT-2 inhibitors given their safety profile,” Dr. Maxwell and colleagues wrote.
For now, pioglitazone “should not be used to prevent dementia in patients with T2DM,” they concluded.
The study was supported by grants from the National Research Foundation of Korea funded by the Korean government and the Ministry of Health and Welfare. The investigators and editorialists report no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
new research suggests.
Overall, in a large cohort study from South Korea, patients who took pioglitazone were 16% less likely to develop dementia over an average of 10 years than peers who did not take the drug.
However, the dementia risk reduction was 54% among those with ischemic heart disease and 43% among those with a history of stroke.
“Our study was to see the association between pioglitazone use and incidence of dementia, not how (with what mechanisms) this drug can suppress dementia pathology,” coinvestigator Eosu Kim, MD, PhD, Yonsei University, Seoul, South Korea, said in an interview.
However, “as we found this drug is more effective in diabetic patients who have blood circulation problems in the heart or brain than in those without such problems, we speculate that pioglitazone’s antidementia action may be related to improving blood vessel’s health,” Dr. Kim said.
This finding suggests that pioglitazone could be used as a personalized treatment approach for dementia prevention in this subgroup of patients with diabetes, the researchers noted.
The results were published online in Neurology.
Dose-response relationship
Risk for dementia is doubled in adults with T2DM, the investigators wrote. Prior studies have suggested that pioglitazone may protect against dementia, as well as a first or recurrent stroke, in patients with T2DM.
This led Dr. Kim and colleagues to examine the effects of pioglitazone on dementia risk overall and in relation to stroke and ischemic heart disease.
Using the national Korean health database, the researchers identified 91,218 adults aged 50 and older with new-onset T2DM who did not have dementia. A total of 3,467 were treated with pioglitazone.
Pioglitazone exposure was defined as a total cumulative daily dose of 90 or more calculated from all dispensations during 4 years after T2DM diagnosis, with outcomes assessed after this period.
Over an average of 10 years, 8.3% of pioglitazone users developed dementia, compared with 10.0% of nonusers.
There was a statistically significant 16% lower risk for developing all-cause dementia among pioglitazone users than among nonusers (adjusted hazard ratio, 0.84; 95% confidence interval, 0.75-0.95).
A dose-response relationship was evident; pioglitazone users who received the highest cumulative daily dose were at lower risk for dementia (aHR, 0.72; 95% CI, 0.55-0.94).
Several limitations
The reduced risk for dementia was more pronounced among patients who used pioglitazone for 4 years in comparison with patients who did not use the drug (aHR, 0.63; 95% CI, 0.44-0.90).
The apparent protective effect of pioglitazone with regard to dementia was greater among those with a history of ischemic heart disease (aHR, 0.46; 95% CI, 0.24-0.90) or stroke (aHR, 0.57; 95% CI, 0.38-0.86) before diabetes diagnosis.
The incidence of stroke was also reduced with pioglitazone use (aHR, 0.81; 95% CI, 0.66-1.0).
“These results provide valuable information on who could potentially benefit from pioglitazone use for prevention of dementia,” Dr. Kim said in a news release.
However, “the risk and benefit balance of long-term use of this drug to prevent dementia should be prospectively assessed,” he said in an interview.
The researchers cautioned that the study was observational; hence, the reported associations cannot address causal relationships. Also, because of the use of claims data, drug compliance could not be guaranteed, and exposure may have been overestimated.
There is also the potential for selection bias, and no information on apolipoprotein E was available, they noted.
More data needed
In an accompanying editorial, Colleen J. Maxwell, PhD, University of Waterloo (Ont.), and colleagues wrote that the results “not only support previous studies showing the potential cognitive benefit of pioglitazone but also extend our understanding of this benefit through the mediating effect of reducing ischemic stroke.”
However, because of their associated risks, which include fractures, weight gain, heart failure, and bladder cancer, thiazolidinediones are not currently favored in diabetes management guidelines – and their use has significantly declined since the mid to late 2000s, the editorialists noted.
They agreed that it will be important to reassess the risk-benefit profile of pioglitazone in T2DM as additional findings emerge.
They also noted that sodium-glucose cotransporter-2 inhibitors, which have significant cardiovascular and renal benefits and minimal side effects, may also lower the risk for dementia.
“As both pioglitazone and SGLT-2 inhibitors are second-line options for physicians, the current decision would easily be in favor of SGLT-2 inhibitors given their safety profile,” Dr. Maxwell and colleagues wrote.
For now, pioglitazone “should not be used to prevent dementia in patients with T2DM,” they concluded.
The study was supported by grants from the National Research Foundation of Korea funded by the Korean government and the Ministry of Health and Welfare. The investigators and editorialists report no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
new research suggests.
Overall, in a large cohort study from South Korea, patients who took pioglitazone were 16% less likely to develop dementia over an average of 10 years than peers who did not take the drug.
However, the dementia risk reduction was 54% among those with ischemic heart disease and 43% among those with a history of stroke.
“Our study was to see the association between pioglitazone use and incidence of dementia, not how (with what mechanisms) this drug can suppress dementia pathology,” coinvestigator Eosu Kim, MD, PhD, Yonsei University, Seoul, South Korea, said in an interview.
However, “as we found this drug is more effective in diabetic patients who have blood circulation problems in the heart or brain than in those without such problems, we speculate that pioglitazone’s antidementia action may be related to improving blood vessel’s health,” Dr. Kim said.
This finding suggests that pioglitazone could be used as a personalized treatment approach for dementia prevention in this subgroup of patients with diabetes, the researchers noted.
The results were published online in Neurology.
Dose-response relationship
Risk for dementia is doubled in adults with T2DM, the investigators wrote. Prior studies have suggested that pioglitazone may protect against dementia, as well as a first or recurrent stroke, in patients with T2DM.
This led Dr. Kim and colleagues to examine the effects of pioglitazone on dementia risk overall and in relation to stroke and ischemic heart disease.
Using the national Korean health database, the researchers identified 91,218 adults aged 50 and older with new-onset T2DM who did not have dementia. A total of 3,467 were treated with pioglitazone.
Pioglitazone exposure was defined as a total cumulative daily dose of 90 or more calculated from all dispensations during 4 years after T2DM diagnosis, with outcomes assessed after this period.
Over an average of 10 years, 8.3% of pioglitazone users developed dementia, compared with 10.0% of nonusers.
There was a statistically significant 16% lower risk for developing all-cause dementia among pioglitazone users than among nonusers (adjusted hazard ratio, 0.84; 95% confidence interval, 0.75-0.95).
A dose-response relationship was evident; pioglitazone users who received the highest cumulative daily dose were at lower risk for dementia (aHR, 0.72; 95% CI, 0.55-0.94).
Several limitations
The reduced risk for dementia was more pronounced among patients who used pioglitazone for 4 years in comparison with patients who did not use the drug (aHR, 0.63; 95% CI, 0.44-0.90).
The apparent protective effect of pioglitazone with regard to dementia was greater among those with a history of ischemic heart disease (aHR, 0.46; 95% CI, 0.24-0.90) or stroke (aHR, 0.57; 95% CI, 0.38-0.86) before diabetes diagnosis.
The incidence of stroke was also reduced with pioglitazone use (aHR, 0.81; 95% CI, 0.66-1.0).
“These results provide valuable information on who could potentially benefit from pioglitazone use for prevention of dementia,” Dr. Kim said in a news release.
However, “the risk and benefit balance of long-term use of this drug to prevent dementia should be prospectively assessed,” he said in an interview.
The researchers cautioned that the study was observational; hence, the reported associations cannot address causal relationships. Also, because of the use of claims data, drug compliance could not be guaranteed, and exposure may have been overestimated.
There is also the potential for selection bias, and no information on apolipoprotein E was available, they noted.
More data needed
In an accompanying editorial, Colleen J. Maxwell, PhD, University of Waterloo (Ont.), and colleagues wrote that the results “not only support previous studies showing the potential cognitive benefit of pioglitazone but also extend our understanding of this benefit through the mediating effect of reducing ischemic stroke.”
However, because of their associated risks, which include fractures, weight gain, heart failure, and bladder cancer, thiazolidinediones are not currently favored in diabetes management guidelines – and their use has significantly declined since the mid to late 2000s, the editorialists noted.
They agreed that it will be important to reassess the risk-benefit profile of pioglitazone in T2DM as additional findings emerge.
They also noted that sodium-glucose cotransporter-2 inhibitors, which have significant cardiovascular and renal benefits and minimal side effects, may also lower the risk for dementia.
“As both pioglitazone and SGLT-2 inhibitors are second-line options for physicians, the current decision would easily be in favor of SGLT-2 inhibitors given their safety profile,” Dr. Maxwell and colleagues wrote.
For now, pioglitazone “should not be used to prevent dementia in patients with T2DM,” they concluded.
The study was supported by grants from the National Research Foundation of Korea funded by the Korean government and the Ministry of Health and Welfare. The investigators and editorialists report no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
FROM NEUROLOGY
What’s new in brain health?
This transcript has been edited for clarity.
Dear colleagues, I am Christoph Diener from the medical faculty of the University of Duisburg-Essen in Germany.
Treatment of tension-type headache
I would like to start with headache. You are all aware that we have several new studies regarding the prevention of migraine, but very few studies involving nondrug treatments for tension-type headache.
A working group in Göttingen, Germany, conducted a study in people with frequent episodic and chronic tension-type headache. The first of the four randomized groups received traditional Chinese acupuncture for 3 months. The second group received physical therapy and exercise for 1 hour per week for 12 weeks. The third group received a combination of acupuncture and exercise. The last was a control group that received only standard care.
The outcome parameters of tension-type headache were evaluated after 6 months and again after 12 months. Previously, these same researchers published that the intensity but not the frequency of tension-type headache was reduced by active therapy.
In Cephalalgia, they published the outcome for the endpoints of depression, anxiety, and quality of life. Acupuncture, exercise, and the combination of the two improved depression, anxiety, and quality of life. This shows that nonmedical treatment is effective in people with frequent episodic and chronic tension-type headache.
Headache after COVID-19
The next study was published in Headache and discusses headache after COVID-19. In this review of published studies, more than 50% of people with COVID-19 develop headache. It is more frequent in young patients and people with preexisting primary headaches, such as migraine and tension-type headache. Prognosis is usually good, but some patients develop new, daily persistent headache, which is a major problem because treatment is unclear. We desperately need studies investigating how to treat this new, daily persistent headache after COVID-19.
SSRIs during COVID-19 infection
The next study also focuses on COVID-19. We have conflicting results from several studies suggesting that selective serotonin reuptake inhibitors might be effective in people with mild COVID-19 infection. This hypothesis was tested in a study in Brazil and was published in JAMA, The study included 1,288 outpatients with mild COVID-19 who either received 50 mg of fluvoxamine twice daily for 10 days or placebo. There was no benefit of the treatment for any outcome.
Preventing dementia with antihypertensive treatment
The next study was published in the European Heart Journal and addresses the question of whether effective antihypertensive treatment in elderly persons can prevent dementia. This is a meta-analysis of five placebo-controlled trials with more than 28,000 patients. The meta-analysis clearly shows that treating hypertension in elderly patients does prevent dementia. The benefit is higher if the blood pressure is lowered by a larger amount which also stays true for elderly patients. There is no negative impact of lowering blood pressure in this population.
Antiplatelet therapy
The next study was published in Stroke and reexamines whether resumption of antiplatelet therapy should be early or late in people who had an intracerebral hemorrhage while on antiplatelet therapy. In the Taiwanese Health Registry, this was studied in 1,584 patients. The researchers divided participants into groups based on whether antiplatelet therapy was resumed within 30 days or after 30 days. In 1 year, the rate of recurrent intracerebral hemorrhage was 3.2%. There was no difference whether antiplatelet therapy was resumed early or late.
Regular exercise in Parkinson’s disease
The final study is a review of nonmedical therapy. This meta-analysis of 19 randomized trials looked at the benefit of regular exercise in patients with Parkinson’s disease and depression. The analysis clearly showed that rigorous and moderate exercise improved depression in patients with Parkinson’s disease. This is very important because exercise improves not only the symptoms of Parkinson’s disease but also comorbid depression while presenting no serious adverse events or side effects.
Dr. Diener is a professor in the department of neurology at Stroke Center–Headache Center, University Duisburg-Essen, Germany. He disclosed ties with Abbott, Addex Pharma, Alder, Allergan, Almirall, Amgen, Autonomic Technology, AstraZeneca, Bayer Vital, Berlin Chemie, Bristol-Myers Squibb, Boehringer Ingelheim, Chordate, CoAxia, Corimmun, Covidien, Coherex, CoLucid, Daiichi Sankyo, D-Pharm, Electrocore, Fresenius, GlaxoSmithKline, Grunenthal, Janssen-Cilag, Labrys Biologics Lilly, La Roche, Lundbeck, 3M Medica, MSD, Medtronic, Menarini, MindFrame, Minster, Neuroscore, Neurobiological Technologies, Novartis, Novo Nordisk, Johnson & Johnson, Knoll, Paion, Parke-Davis, Pierre Fabre, Pfizer Inc, Schaper and Brummer, Sanofi-Aventis, Schering-Plough, Servier, Solvay, St. Jude, Talecris, Thrombogenics, WebMD Global, Weber and Weber, Wyeth, and Yamanouchi. Dr. Diener has served as editor of Aktuelle Neurologie, Arzneimitteltherapie, Kopfschmerz News, Stroke News, and the Treatment Guidelines of the German Neurological Society; as co-editor of Cephalalgia; and on the editorial board of The Lancet Neurology, Stroke, European Neurology, and Cerebrovascular Disorders. The department of neurology in Essen is supported by the German Research Council, the German Ministry of Education and Research, European Union, National Institutes of Health, Bertelsmann Foundation, and Heinz Nixdorf Foundation. Dr. Diener has no ownership interest and does not own stocks in any pharmaceutical company. A version of this article originally appeared on Medscape.com.
This transcript has been edited for clarity.
Dear colleagues, I am Christoph Diener from the medical faculty of the University of Duisburg-Essen in Germany.
Treatment of tension-type headache
I would like to start with headache. You are all aware that we have several new studies regarding the prevention of migraine, but very few studies involving nondrug treatments for tension-type headache.
A working group in Göttingen, Germany, conducted a study in people with frequent episodic and chronic tension-type headache. The first of the four randomized groups received traditional Chinese acupuncture for 3 months. The second group received physical therapy and exercise for 1 hour per week for 12 weeks. The third group received a combination of acupuncture and exercise. The last was a control group that received only standard care.
The outcome parameters of tension-type headache were evaluated after 6 months and again after 12 months. Previously, these same researchers published that the intensity but not the frequency of tension-type headache was reduced by active therapy.
In Cephalalgia, they published the outcome for the endpoints of depression, anxiety, and quality of life. Acupuncture, exercise, and the combination of the two improved depression, anxiety, and quality of life. This shows that nonmedical treatment is effective in people with frequent episodic and chronic tension-type headache.
Headache after COVID-19
The next study was published in Headache and discusses headache after COVID-19. In this review of published studies, more than 50% of people with COVID-19 develop headache. It is more frequent in young patients and people with preexisting primary headaches, such as migraine and tension-type headache. Prognosis is usually good, but some patients develop new, daily persistent headache, which is a major problem because treatment is unclear. We desperately need studies investigating how to treat this new, daily persistent headache after COVID-19.
SSRIs during COVID-19 infection
The next study also focuses on COVID-19. We have conflicting results from several studies suggesting that selective serotonin reuptake inhibitors might be effective in people with mild COVID-19 infection. This hypothesis was tested in a study in Brazil and was published in JAMA, The study included 1,288 outpatients with mild COVID-19 who either received 50 mg of fluvoxamine twice daily for 10 days or placebo. There was no benefit of the treatment for any outcome.
Preventing dementia with antihypertensive treatment
The next study was published in the European Heart Journal and addresses the question of whether effective antihypertensive treatment in elderly persons can prevent dementia. This is a meta-analysis of five placebo-controlled trials with more than 28,000 patients. The meta-analysis clearly shows that treating hypertension in elderly patients does prevent dementia. The benefit is higher if the blood pressure is lowered by a larger amount which also stays true for elderly patients. There is no negative impact of lowering blood pressure in this population.
Antiplatelet therapy
The next study was published in Stroke and reexamines whether resumption of antiplatelet therapy should be early or late in people who had an intracerebral hemorrhage while on antiplatelet therapy. In the Taiwanese Health Registry, this was studied in 1,584 patients. The researchers divided participants into groups based on whether antiplatelet therapy was resumed within 30 days or after 30 days. In 1 year, the rate of recurrent intracerebral hemorrhage was 3.2%. There was no difference whether antiplatelet therapy was resumed early or late.
Regular exercise in Parkinson’s disease
The final study is a review of nonmedical therapy. This meta-analysis of 19 randomized trials looked at the benefit of regular exercise in patients with Parkinson’s disease and depression. The analysis clearly showed that rigorous and moderate exercise improved depression in patients with Parkinson’s disease. This is very important because exercise improves not only the symptoms of Parkinson’s disease but also comorbid depression while presenting no serious adverse events or side effects.
Dr. Diener is a professor in the department of neurology at Stroke Center–Headache Center, University Duisburg-Essen, Germany. He disclosed ties with Abbott, Addex Pharma, Alder, Allergan, Almirall, Amgen, Autonomic Technology, AstraZeneca, Bayer Vital, Berlin Chemie, Bristol-Myers Squibb, Boehringer Ingelheim, Chordate, CoAxia, Corimmun, Covidien, Coherex, CoLucid, Daiichi Sankyo, D-Pharm, Electrocore, Fresenius, GlaxoSmithKline, Grunenthal, Janssen-Cilag, Labrys Biologics Lilly, La Roche, Lundbeck, 3M Medica, MSD, Medtronic, Menarini, MindFrame, Minster, Neuroscore, Neurobiological Technologies, Novartis, Novo Nordisk, Johnson & Johnson, Knoll, Paion, Parke-Davis, Pierre Fabre, Pfizer Inc, Schaper and Brummer, Sanofi-Aventis, Schering-Plough, Servier, Solvay, St. Jude, Talecris, Thrombogenics, WebMD Global, Weber and Weber, Wyeth, and Yamanouchi. Dr. Diener has served as editor of Aktuelle Neurologie, Arzneimitteltherapie, Kopfschmerz News, Stroke News, and the Treatment Guidelines of the German Neurological Society; as co-editor of Cephalalgia; and on the editorial board of The Lancet Neurology, Stroke, European Neurology, and Cerebrovascular Disorders. The department of neurology in Essen is supported by the German Research Council, the German Ministry of Education and Research, European Union, National Institutes of Health, Bertelsmann Foundation, and Heinz Nixdorf Foundation. Dr. Diener has no ownership interest and does not own stocks in any pharmaceutical company. A version of this article originally appeared on Medscape.com.
This transcript has been edited for clarity.
Dear colleagues, I am Christoph Diener from the medical faculty of the University of Duisburg-Essen in Germany.
Treatment of tension-type headache
I would like to start with headache. You are all aware that we have several new studies regarding the prevention of migraine, but very few studies involving nondrug treatments for tension-type headache.
A working group in Göttingen, Germany, conducted a study in people with frequent episodic and chronic tension-type headache. The first of the four randomized groups received traditional Chinese acupuncture for 3 months. The second group received physical therapy and exercise for 1 hour per week for 12 weeks. The third group received a combination of acupuncture and exercise. The last was a control group that received only standard care.
The outcome parameters of tension-type headache were evaluated after 6 months and again after 12 months. Previously, these same researchers published that the intensity but not the frequency of tension-type headache was reduced by active therapy.
In Cephalalgia, they published the outcome for the endpoints of depression, anxiety, and quality of life. Acupuncture, exercise, and the combination of the two improved depression, anxiety, and quality of life. This shows that nonmedical treatment is effective in people with frequent episodic and chronic tension-type headache.
Headache after COVID-19
The next study was published in Headache and discusses headache after COVID-19. In this review of published studies, more than 50% of people with COVID-19 develop headache. It is more frequent in young patients and people with preexisting primary headaches, such as migraine and tension-type headache. Prognosis is usually good, but some patients develop new, daily persistent headache, which is a major problem because treatment is unclear. We desperately need studies investigating how to treat this new, daily persistent headache after COVID-19.
SSRIs during COVID-19 infection
The next study also focuses on COVID-19. We have conflicting results from several studies suggesting that selective serotonin reuptake inhibitors might be effective in people with mild COVID-19 infection. This hypothesis was tested in a study in Brazil and was published in JAMA, The study included 1,288 outpatients with mild COVID-19 who either received 50 mg of fluvoxamine twice daily for 10 days or placebo. There was no benefit of the treatment for any outcome.
Preventing dementia with antihypertensive treatment
The next study was published in the European Heart Journal and addresses the question of whether effective antihypertensive treatment in elderly persons can prevent dementia. This is a meta-analysis of five placebo-controlled trials with more than 28,000 patients. The meta-analysis clearly shows that treating hypertension in elderly patients does prevent dementia. The benefit is higher if the blood pressure is lowered by a larger amount which also stays true for elderly patients. There is no negative impact of lowering blood pressure in this population.
Antiplatelet therapy
The next study was published in Stroke and reexamines whether resumption of antiplatelet therapy should be early or late in people who had an intracerebral hemorrhage while on antiplatelet therapy. In the Taiwanese Health Registry, this was studied in 1,584 patients. The researchers divided participants into groups based on whether antiplatelet therapy was resumed within 30 days or after 30 days. In 1 year, the rate of recurrent intracerebral hemorrhage was 3.2%. There was no difference whether antiplatelet therapy was resumed early or late.
Regular exercise in Parkinson’s disease
The final study is a review of nonmedical therapy. This meta-analysis of 19 randomized trials looked at the benefit of regular exercise in patients with Parkinson’s disease and depression. The analysis clearly showed that rigorous and moderate exercise improved depression in patients with Parkinson’s disease. This is very important because exercise improves not only the symptoms of Parkinson’s disease but also comorbid depression while presenting no serious adverse events or side effects.
Dr. Diener is a professor in the department of neurology at Stroke Center–Headache Center, University Duisburg-Essen, Germany. He disclosed ties with Abbott, Addex Pharma, Alder, Allergan, Almirall, Amgen, Autonomic Technology, AstraZeneca, Bayer Vital, Berlin Chemie, Bristol-Myers Squibb, Boehringer Ingelheim, Chordate, CoAxia, Corimmun, Covidien, Coherex, CoLucid, Daiichi Sankyo, D-Pharm, Electrocore, Fresenius, GlaxoSmithKline, Grunenthal, Janssen-Cilag, Labrys Biologics Lilly, La Roche, Lundbeck, 3M Medica, MSD, Medtronic, Menarini, MindFrame, Minster, Neuroscore, Neurobiological Technologies, Novartis, Novo Nordisk, Johnson & Johnson, Knoll, Paion, Parke-Davis, Pierre Fabre, Pfizer Inc, Schaper and Brummer, Sanofi-Aventis, Schering-Plough, Servier, Solvay, St. Jude, Talecris, Thrombogenics, WebMD Global, Weber and Weber, Wyeth, and Yamanouchi. Dr. Diener has served as editor of Aktuelle Neurologie, Arzneimitteltherapie, Kopfschmerz News, Stroke News, and the Treatment Guidelines of the German Neurological Society; as co-editor of Cephalalgia; and on the editorial board of The Lancet Neurology, Stroke, European Neurology, and Cerebrovascular Disorders. The department of neurology in Essen is supported by the German Research Council, the German Ministry of Education and Research, European Union, National Institutes of Health, Bertelsmann Foundation, and Heinz Nixdorf Foundation. Dr. Diener has no ownership interest and does not own stocks in any pharmaceutical company. A version of this article originally appeared on Medscape.com.
Three wild technologies about to change health care
When I was a child, I watched syndicated episodes of the original “Star Trek.” I was dazzled by the space travel, sure, but also the medical technology.
A handheld “tricorder” detected diseases, while an intramuscular injector (“hypospray”) could treat them. Sickbay “biobeds” came with real-time health monitors that looked futuristic at the time but seem primitive today.
Such visions inspired a lot of us kids to pursue science. Little did we know the real-life advances many of us would see in our lifetimes.
Artificial intelligence helping to spot disease, robots performing surgery, even video calls between doctor and patient – all these once sounded fantastical but now happen in clinical care.
Now, in the 23rd year of the 21st century, you might not believe wht we’ll be capable of next. Three especially wild examples are moving closer to clinical reality.
Human hibernation
Captain America, Han Solo, and “Star Trek” villain Khan – all were preserved at low temperatures and then revived, waking up alive and well months, decades, or centuries later. These are fictional examples, to be sure, but the science they’re rooted in is real.
(In one extreme case, a climber survived after almost 9 hours of efforts to revive him.)
Useful for a space traveler? Maybe not. But it’s potentially huge for someone with life-threatening injuries from a car accident or a gunshot wound.
That’s the thinking behind a breakthrough procedure that came after decades of research on pigs and dogs, now in a clinical trial. The idea: A person with massive blood loss whose heart has stopped is injected with an ice-cold fluid, cooling them from the inside, down to about 50° F.
Doctors already induce more modest hypothermia to protect the brain and other organs after cardiac arrest and during surgery on the aortic arch (the main artery carrying blood from the heart).
But this experimental procedure – called emergency preservation and resuscitation (EPR) – goes far beyond that, dramatically “decreasing the body’s need for oxygen and blood flow,” says Samuel Tisherman, MD, a trauma surgeon at the University of Maryland Medical Center and the trial’s lead researcher. This puts the patient in a state of suspended animation that “could buy time for surgeons to stop the bleeding and save more of these patients.”
The technique has been done on at least six patients, though none were reported to survive. The trial is expected to include 20 people by the time it wraps up in December, according to the listing on the U.S. clinical trials database. Though given the strict requirements for candidates (emergency trauma victims who are not likely to survive), one can’t exactly rely on a set schedule.
Still, the technology is promising. Someday we may even use it to keep patients in suspended animation for months or years, experts predict, helping astronauts through decades-long spaceflights, or stalling death in sick patients awaiting a cure.
Artificial womb
Another sci-fi classic: growing human babies outside the womb. Think the fetus fields from “The Matrix,” or the frozen embryos in “Alien: Covenant.”
In 1923, British biologist J.B.S. Haldane coined a term for that – ectogenesis. He predicted that 70% of pregnancies would take place, from fertilization to birth, in artificial wombs by 2074. That many seems unlikely, but the timeline is on track.
Developing an embryo outside the womb is already routine in in vitro fertilization. And technology enables preterm babies to survive through much of the second half of gestation. Normal human pregnancy is 40 weeks, and the youngest preterm baby ever to survive was 21 weeks and 1 day old, just a few days younger than a smattering of others who lived.
The biggest obstacle for babies younger than that is lung viability. Mechanical ventilation can damage the lungs and lead to a chronic (sometimes fatal) lung disease known as bronchopulmonary dysplasia. Avoiding this would mean figuring out a way to maintain fetal circulation – the intricate system that delivers oxygenated blood from the placenta to the fetus via the umbilical cord. Researchers at Children’s Hospital of Philadelphia have done this using a fetal lamb.
The key to their invention is a substitute placenta: an oxygenator connected to the lamb’s umbilical cord. Tubes inserted through the umbilical vein and arteries carry oxygenated blood from the “placenta” to the fetus, and deoxygenated blood back out. The lamb resides in an artificial, fluid-filled amniotic sac until its lungs and other organs are developed.
Fertility treatment could benefit, too. “An artificial womb may substitute in situations in which a gestational carrier – surrogate – is indicated,” says Paula Amato, MD, a professor of obstetrics and gynecology at Oregon Health and Science University, Portland. (Dr. Amato is not involved in the CHOP research.) For example: when the mother is missing a uterus or can’t carry a pregnancy safely.
No date is set for clinical trials yet. But according to the research, the main difference between human and lamb may come down to size. A lamb’s umbilical vessels are larger, so feeding in a tube is easier. With today’s advances in miniaturizing surgical methods, that seems like a challenge scientists can overcome.
Messenger RNA therapeutics
Back to “Star Trek.” The hypospray injector’s contents could cure just about any disease, even one newly discovered on a strange planet. That’s not unlike messenger RNA (mRNA) technology, a breakthrough that enabled scientists to quickly develop some of the first COVID-19 vaccines.
But vaccines are just the beginning of what this technology can do.
A whole field of immunotherapy is emerging that uses mRNA to deliver instructions to produce chimeric antigen receptor–modified immune cells (CAR-modified immune cells). These cells are engineered to target diseased cells and tissues, like cancer cells and harmful fibroblasts (scar tissue) that promote fibrosis in, for example, the heart and lungs.
The field is bursting with rodent research, and clinical trials have started for treating some advanced-stage malignancies.
Actual clinical use may be years away, but if all goes well, these medicines could help treat or even cure the core medical problems facing humanity. We’re talking cancer, heart disease, neurodegenerative disease – transforming one therapy into another by simply changing the mRNA’s “nucleotide sequence,” the blueprint containing instructions telling it what to do, and what disease to attack.
As this technology matures, we may start to feel as if we’re really on “Star Trek,” where Dr. Leonard “Bones” McCoy pulls out the same device to treat just about every disease or injury.
A version of this article first appeared on WebMD.com.
When I was a child, I watched syndicated episodes of the original “Star Trek.” I was dazzled by the space travel, sure, but also the medical technology.
A handheld “tricorder” detected diseases, while an intramuscular injector (“hypospray”) could treat them. Sickbay “biobeds” came with real-time health monitors that looked futuristic at the time but seem primitive today.
Such visions inspired a lot of us kids to pursue science. Little did we know the real-life advances many of us would see in our lifetimes.
Artificial intelligence helping to spot disease, robots performing surgery, even video calls between doctor and patient – all these once sounded fantastical but now happen in clinical care.
Now, in the 23rd year of the 21st century, you might not believe wht we’ll be capable of next. Three especially wild examples are moving closer to clinical reality.
Human hibernation
Captain America, Han Solo, and “Star Trek” villain Khan – all were preserved at low temperatures and then revived, waking up alive and well months, decades, or centuries later. These are fictional examples, to be sure, but the science they’re rooted in is real.
(In one extreme case, a climber survived after almost 9 hours of efforts to revive him.)
Useful for a space traveler? Maybe not. But it’s potentially huge for someone with life-threatening injuries from a car accident or a gunshot wound.
That’s the thinking behind a breakthrough procedure that came after decades of research on pigs and dogs, now in a clinical trial. The idea: A person with massive blood loss whose heart has stopped is injected with an ice-cold fluid, cooling them from the inside, down to about 50° F.
Doctors already induce more modest hypothermia to protect the brain and other organs after cardiac arrest and during surgery on the aortic arch (the main artery carrying blood from the heart).
But this experimental procedure – called emergency preservation and resuscitation (EPR) – goes far beyond that, dramatically “decreasing the body’s need for oxygen and blood flow,” says Samuel Tisherman, MD, a trauma surgeon at the University of Maryland Medical Center and the trial’s lead researcher. This puts the patient in a state of suspended animation that “could buy time for surgeons to stop the bleeding and save more of these patients.”
The technique has been done on at least six patients, though none were reported to survive. The trial is expected to include 20 people by the time it wraps up in December, according to the listing on the U.S. clinical trials database. Though given the strict requirements for candidates (emergency trauma victims who are not likely to survive), one can’t exactly rely on a set schedule.
Still, the technology is promising. Someday we may even use it to keep patients in suspended animation for months or years, experts predict, helping astronauts through decades-long spaceflights, or stalling death in sick patients awaiting a cure.
Artificial womb
Another sci-fi classic: growing human babies outside the womb. Think the fetus fields from “The Matrix,” or the frozen embryos in “Alien: Covenant.”
In 1923, British biologist J.B.S. Haldane coined a term for that – ectogenesis. He predicted that 70% of pregnancies would take place, from fertilization to birth, in artificial wombs by 2074. That many seems unlikely, but the timeline is on track.
Developing an embryo outside the womb is already routine in in vitro fertilization. And technology enables preterm babies to survive through much of the second half of gestation. Normal human pregnancy is 40 weeks, and the youngest preterm baby ever to survive was 21 weeks and 1 day old, just a few days younger than a smattering of others who lived.
The biggest obstacle for babies younger than that is lung viability. Mechanical ventilation can damage the lungs and lead to a chronic (sometimes fatal) lung disease known as bronchopulmonary dysplasia. Avoiding this would mean figuring out a way to maintain fetal circulation – the intricate system that delivers oxygenated blood from the placenta to the fetus via the umbilical cord. Researchers at Children’s Hospital of Philadelphia have done this using a fetal lamb.
The key to their invention is a substitute placenta: an oxygenator connected to the lamb’s umbilical cord. Tubes inserted through the umbilical vein and arteries carry oxygenated blood from the “placenta” to the fetus, and deoxygenated blood back out. The lamb resides in an artificial, fluid-filled amniotic sac until its lungs and other organs are developed.
Fertility treatment could benefit, too. “An artificial womb may substitute in situations in which a gestational carrier – surrogate – is indicated,” says Paula Amato, MD, a professor of obstetrics and gynecology at Oregon Health and Science University, Portland. (Dr. Amato is not involved in the CHOP research.) For example: when the mother is missing a uterus or can’t carry a pregnancy safely.
No date is set for clinical trials yet. But according to the research, the main difference between human and lamb may come down to size. A lamb’s umbilical vessels are larger, so feeding in a tube is easier. With today’s advances in miniaturizing surgical methods, that seems like a challenge scientists can overcome.
Messenger RNA therapeutics
Back to “Star Trek.” The hypospray injector’s contents could cure just about any disease, even one newly discovered on a strange planet. That’s not unlike messenger RNA (mRNA) technology, a breakthrough that enabled scientists to quickly develop some of the first COVID-19 vaccines.
But vaccines are just the beginning of what this technology can do.
A whole field of immunotherapy is emerging that uses mRNA to deliver instructions to produce chimeric antigen receptor–modified immune cells (CAR-modified immune cells). These cells are engineered to target diseased cells and tissues, like cancer cells and harmful fibroblasts (scar tissue) that promote fibrosis in, for example, the heart and lungs.
The field is bursting with rodent research, and clinical trials have started for treating some advanced-stage malignancies.
Actual clinical use may be years away, but if all goes well, these medicines could help treat or even cure the core medical problems facing humanity. We’re talking cancer, heart disease, neurodegenerative disease – transforming one therapy into another by simply changing the mRNA’s “nucleotide sequence,” the blueprint containing instructions telling it what to do, and what disease to attack.
As this technology matures, we may start to feel as if we’re really on “Star Trek,” where Dr. Leonard “Bones” McCoy pulls out the same device to treat just about every disease or injury.
A version of this article first appeared on WebMD.com.
When I was a child, I watched syndicated episodes of the original “Star Trek.” I was dazzled by the space travel, sure, but also the medical technology.
A handheld “tricorder” detected diseases, while an intramuscular injector (“hypospray”) could treat them. Sickbay “biobeds” came with real-time health monitors that looked futuristic at the time but seem primitive today.
Such visions inspired a lot of us kids to pursue science. Little did we know the real-life advances many of us would see in our lifetimes.
Artificial intelligence helping to spot disease, robots performing surgery, even video calls between doctor and patient – all these once sounded fantastical but now happen in clinical care.
Now, in the 23rd year of the 21st century, you might not believe wht we’ll be capable of next. Three especially wild examples are moving closer to clinical reality.
Human hibernation
Captain America, Han Solo, and “Star Trek” villain Khan – all were preserved at low temperatures and then revived, waking up alive and well months, decades, or centuries later. These are fictional examples, to be sure, but the science they’re rooted in is real.
(In one extreme case, a climber survived after almost 9 hours of efforts to revive him.)
Useful for a space traveler? Maybe not. But it’s potentially huge for someone with life-threatening injuries from a car accident or a gunshot wound.
That’s the thinking behind a breakthrough procedure that came after decades of research on pigs and dogs, now in a clinical trial. The idea: A person with massive blood loss whose heart has stopped is injected with an ice-cold fluid, cooling them from the inside, down to about 50° F.
Doctors already induce more modest hypothermia to protect the brain and other organs after cardiac arrest and during surgery on the aortic arch (the main artery carrying blood from the heart).
But this experimental procedure – called emergency preservation and resuscitation (EPR) – goes far beyond that, dramatically “decreasing the body’s need for oxygen and blood flow,” says Samuel Tisherman, MD, a trauma surgeon at the University of Maryland Medical Center and the trial’s lead researcher. This puts the patient in a state of suspended animation that “could buy time for surgeons to stop the bleeding and save more of these patients.”
The technique has been done on at least six patients, though none were reported to survive. The trial is expected to include 20 people by the time it wraps up in December, according to the listing on the U.S. clinical trials database. Though given the strict requirements for candidates (emergency trauma victims who are not likely to survive), one can’t exactly rely on a set schedule.
Still, the technology is promising. Someday we may even use it to keep patients in suspended animation for months or years, experts predict, helping astronauts through decades-long spaceflights, or stalling death in sick patients awaiting a cure.
Artificial womb
Another sci-fi classic: growing human babies outside the womb. Think the fetus fields from “The Matrix,” or the frozen embryos in “Alien: Covenant.”
In 1923, British biologist J.B.S. Haldane coined a term for that – ectogenesis. He predicted that 70% of pregnancies would take place, from fertilization to birth, in artificial wombs by 2074. That many seems unlikely, but the timeline is on track.
Developing an embryo outside the womb is already routine in in vitro fertilization. And technology enables preterm babies to survive through much of the second half of gestation. Normal human pregnancy is 40 weeks, and the youngest preterm baby ever to survive was 21 weeks and 1 day old, just a few days younger than a smattering of others who lived.
The biggest obstacle for babies younger than that is lung viability. Mechanical ventilation can damage the lungs and lead to a chronic (sometimes fatal) lung disease known as bronchopulmonary dysplasia. Avoiding this would mean figuring out a way to maintain fetal circulation – the intricate system that delivers oxygenated blood from the placenta to the fetus via the umbilical cord. Researchers at Children’s Hospital of Philadelphia have done this using a fetal lamb.
The key to their invention is a substitute placenta: an oxygenator connected to the lamb’s umbilical cord. Tubes inserted through the umbilical vein and arteries carry oxygenated blood from the “placenta” to the fetus, and deoxygenated blood back out. The lamb resides in an artificial, fluid-filled amniotic sac until its lungs and other organs are developed.
Fertility treatment could benefit, too. “An artificial womb may substitute in situations in which a gestational carrier – surrogate – is indicated,” says Paula Amato, MD, a professor of obstetrics and gynecology at Oregon Health and Science University, Portland. (Dr. Amato is not involved in the CHOP research.) For example: when the mother is missing a uterus or can’t carry a pregnancy safely.
No date is set for clinical trials yet. But according to the research, the main difference between human and lamb may come down to size. A lamb’s umbilical vessels are larger, so feeding in a tube is easier. With today’s advances in miniaturizing surgical methods, that seems like a challenge scientists can overcome.
Messenger RNA therapeutics
Back to “Star Trek.” The hypospray injector’s contents could cure just about any disease, even one newly discovered on a strange planet. That’s not unlike messenger RNA (mRNA) technology, a breakthrough that enabled scientists to quickly develop some of the first COVID-19 vaccines.
But vaccines are just the beginning of what this technology can do.
A whole field of immunotherapy is emerging that uses mRNA to deliver instructions to produce chimeric antigen receptor–modified immune cells (CAR-modified immune cells). These cells are engineered to target diseased cells and tissues, like cancer cells and harmful fibroblasts (scar tissue) that promote fibrosis in, for example, the heart and lungs.
The field is bursting with rodent research, and clinical trials have started for treating some advanced-stage malignancies.
Actual clinical use may be years away, but if all goes well, these medicines could help treat or even cure the core medical problems facing humanity. We’re talking cancer, heart disease, neurodegenerative disease – transforming one therapy into another by simply changing the mRNA’s “nucleotide sequence,” the blueprint containing instructions telling it what to do, and what disease to attack.
As this technology matures, we may start to feel as if we’re really on “Star Trek,” where Dr. Leonard “Bones” McCoy pulls out the same device to treat just about every disease or injury.
A version of this article first appeared on WebMD.com.
Drinking tea can keep your heart healthy as you age
according to the Heart Foundation and researchers from Edith Cowan University, Perth, Australia.
What to know
- Elderly women who drank black tea on a regular basis or consumed a high level of flavonoids in their diet were found to be far less likely to develop extensive AAC.
- AAC is calcification of the large artery that supplies oxygenated blood from the heart to the abdominal organs and lower limbs. It is associated with cardiovascular disorders, such as heart attack and stroke, as well as late-life dementia.
- Flavonoids are naturally occurring substances that regulate cellular activity. They are found in many common foods and beverages, such as black tea, green tea, apples, nuts, citrus fruit, berries, red wine, dark chocolate, and others.
- Study participants who had a higher intake of total flavonoids, flavan-3-ols, and flavonols were almost 40% less likely to have extensive AAC, while those who drank two to six cups of black tea per day had up to 42% less chance of experiencing extensive AAC.
- People who do not drink tea can still benefit by including foods rich in flavonoids in their diet, which protects against extensive calcification of the arteries.
This is a summary of the article, “Higher Habitual Dietary Flavonoid Intake Associates With Less Extensive Abdominal Aortic Calcification in a Cohort of Older Women,” published in Arteriosclerosis, Thrombosis, and Vascular Biology on Nov. 2, 2022. The full article can be found on ahajournals.org. A version of this article originally appeared on Medscape.com.
according to the Heart Foundation and researchers from Edith Cowan University, Perth, Australia.
What to know
- Elderly women who drank black tea on a regular basis or consumed a high level of flavonoids in their diet were found to be far less likely to develop extensive AAC.
- AAC is calcification of the large artery that supplies oxygenated blood from the heart to the abdominal organs and lower limbs. It is associated with cardiovascular disorders, such as heart attack and stroke, as well as late-life dementia.
- Flavonoids are naturally occurring substances that regulate cellular activity. They are found in many common foods and beverages, such as black tea, green tea, apples, nuts, citrus fruit, berries, red wine, dark chocolate, and others.
- Study participants who had a higher intake of total flavonoids, flavan-3-ols, and flavonols were almost 40% less likely to have extensive AAC, while those who drank two to six cups of black tea per day had up to 42% less chance of experiencing extensive AAC.
- People who do not drink tea can still benefit by including foods rich in flavonoids in their diet, which protects against extensive calcification of the arteries.
This is a summary of the article, “Higher Habitual Dietary Flavonoid Intake Associates With Less Extensive Abdominal Aortic Calcification in a Cohort of Older Women,” published in Arteriosclerosis, Thrombosis, and Vascular Biology on Nov. 2, 2022. The full article can be found on ahajournals.org. A version of this article originally appeared on Medscape.com.
according to the Heart Foundation and researchers from Edith Cowan University, Perth, Australia.
What to know
- Elderly women who drank black tea on a regular basis or consumed a high level of flavonoids in their diet were found to be far less likely to develop extensive AAC.
- AAC is calcification of the large artery that supplies oxygenated blood from the heart to the abdominal organs and lower limbs. It is associated with cardiovascular disorders, such as heart attack and stroke, as well as late-life dementia.
- Flavonoids are naturally occurring substances that regulate cellular activity. They are found in many common foods and beverages, such as black tea, green tea, apples, nuts, citrus fruit, berries, red wine, dark chocolate, and others.
- Study participants who had a higher intake of total flavonoids, flavan-3-ols, and flavonols were almost 40% less likely to have extensive AAC, while those who drank two to six cups of black tea per day had up to 42% less chance of experiencing extensive AAC.
- People who do not drink tea can still benefit by including foods rich in flavonoids in their diet, which protects against extensive calcification of the arteries.
This is a summary of the article, “Higher Habitual Dietary Flavonoid Intake Associates With Less Extensive Abdominal Aortic Calcification in a Cohort of Older Women,” published in Arteriosclerosis, Thrombosis, and Vascular Biology on Nov. 2, 2022. The full article can be found on ahajournals.org. A version of this article originally appeared on Medscape.com.
If a saphenous graft is available, treat limb threatening ischemia surgically
CHICAGO – In patients with chronic limb-threatening ischemia (CLTI) and a usable saphenous vein segment, a surgical procedure leads to better outcomes than an endovascular approach, according results of the multinational randomized BEST-CLI trial.
In that study, conducted with two cohorts, the advantage of surgery was limited to the group with an available saphenous vein, but in this group the advantage over an endovascular approach was substantial, according to Alik Farber, MD, chief of vascular and endovascular surgery at Boston University.
“Bypass with adequate saphenous vein should be offered as a first-line treatment option for suitable candidates with CLTI as part of fully informed, shared decision-making,” Dr. Farber stated in presenting the results at the annual scientific sessions of the American Heart Association.
The study pursued two hypotheses, which is why CLTI patients were divided into two cohorts. For cohort 1, which was limited to CLTI patients with an available saphenous vein, it was predicted that surgery would be better than an endovascular approach. For cohort 2, which enrolled patients who needed an alternative conduit, the hypothesis was that endovascular procedures would prove superior.
The study confirmed the first hypothesis, but there was no difference between the two approaches for the composite primary outcome of major adverse limb events (MALE) in the second cohort.
Saphenous vein availability determined cohort
Candidates for the BEST-CLI (Best Endovascular versus Best Surgical Therapy in Patients with CLTI) trial had to have CLTI producing severe ischemia and to be judged by both surgeons and cardiovascular specialists to be candidates for both types of interventions. Eligible patients were then enrolled in cohort 1 if the saphenous vein was considered the best conduit on imaging. If not, they were enrolled in cohort 2.
Patients were randomized to undergo surgical or endovascular repair only after the cohort was assigned. The primary composite MALE endpoint consisted of an adjudicated first major reintervention, such as new bypass or thrombectomy, an above-the-ankle amputation, or death from any cause.
In cohort 1, the primary composite MALE endpoint was reached in 42.6% of those in surgical arm and 57.4% in the endovascular arm, translating into a 32% relative risk reduction (hazard ratio, 0.68; P < .001) in favor of surgery at the end of a median of 2.7 years of follow-up.
The main advantage was the difference in reinterventions. The lower rate in the surgical group (9.2% vs. 23.5%), translated into a 65% relative risk reduction for this endpoint (HR, 035; P < .001).
The reduction in above-ankle amputations in the surgical group (10.4% vs. 14.9%) was also significant (HR, 0.73; P = .04), but the reduction in all-cause mortality (33.0% vs. 37.6%) was not (HR, 0.98; P = .81).
BEST-CLI involved 150 sites in North America, Europe, and New Zealand. Cohort 1, which randomized 1,434 patients, was the larger of the two. In the second cohort, only 396 patients were randomized, which Dr. Farber said “might have been underpowered.”
The results were published in the New England Journal of Medicine simultaneously with presentation of the results at the meeting.
After a median follow-up of 1.6 years in cohort 2, the slightly lower proportion of patients who reached the composite MALE endpoint in the surgical group relative to the endovascular group (42.8% vs. 47.7%) did not translate into a significant advantage (HR, 0.79; P = .12).
For the individual components, the lower rate of reinterventions in the surgical arm (14.4% vs. 25.6%) did reach statistical significance (HR, 0.47; P = .002), but both amputation (14.9% vs. 14.1%) and all-cause death (26.3% vs. 24.1%) were numerically but not significantly higher in the surgical group.
The primary safety endpoint was major adverse cardiovascular events (MACE). This was not significantly different in either cohort. There were also no major differences between groups in the risk of perioperative complications.
Level 1 evidence provided for intervention choice
Overall, BEST-CLI showed that both surgical and endovascular revascularizations are effective and safe, according to Dr. Farber. As a result, he suggested that both can be considered even if a saphenous vein is available when specific patient characteristics make one more attractive than another.
Yet, in a general population with an available saphenous vein, these data provide “level 1 evidence” that a surgical approach should be the dominant choice, he added.
A quality of life (QOL) substudy of BEST-CLI did not challenge this conclusion. Rather, the main finding was that restoring circulation by either approach has a major favorable impact on patient well-being, according to Matthew Menard, MD, codirector of endovascular surgery at Brigham and Women’s Hospital, Boston.
In this substudy, presented separately from the primary BEST-CLI results, that analysis confirmed that baseline QOL was extremely poor, whether measured with a disease specific instrument such as VascuQol, or generic instruments, such as SF-12.
Surgical or endovascular treatment produced clinically meaningful and sustained improvements in every QOL measure employed, according to Dr. Menard, and this was true in either cohort.
Results not necessarily relevant to all
These data are likely relevant to the patients evaluated, but “it is important to consider who made it into this trial,” according to Naomi M. Hamburg, MD, section chief of vascular biology at Boston University.
Not least, patients had to be candidates for either surgical or endovascular repair to get into the study, omitting those patients not deemed by the investigators to be suited for either.
In addition, Dr. Hamburg pointed out that there was a low enrollment of Blacks (20%) and women (28%), two groups for whom CTLI is a common condition.
Lastly, Dr Hamburg questioned whether specific types of anatomy might be better suited to one procedure relative to another, a variable not considered in this study. Reassured by Dr. Farber that this will be explored in subsequent analyses of BEST-CLI data, Dr. Hamburg expressed interest in learning the results.
Dr. Hamburg was among those who spoke about the growing urgency to optimize strategies for early diagnosis and treatment of CTLI. She plugged the PAD National Action Plan as one of the efforts to thwart the coming wave of CTLI expected from the steep climb in the prevalence of diabetes in the United States.
Dr. Farber reported a financial relationship with Sanifit Therapeutics. The study was funded by the National Heart, Lung, and Blood Institute, but received additional support from multiple pharmaceutical companies. Dr. Menard reported a financial relationship with Janssen Pharmaceuticals. Dr. Hamburg reported financial relationships with Acceleron Pharma, Merck, NovoNordisk, and Sanifit.
CHICAGO – In patients with chronic limb-threatening ischemia (CLTI) and a usable saphenous vein segment, a surgical procedure leads to better outcomes than an endovascular approach, according results of the multinational randomized BEST-CLI trial.
In that study, conducted with two cohorts, the advantage of surgery was limited to the group with an available saphenous vein, but in this group the advantage over an endovascular approach was substantial, according to Alik Farber, MD, chief of vascular and endovascular surgery at Boston University.
“Bypass with adequate saphenous vein should be offered as a first-line treatment option for suitable candidates with CLTI as part of fully informed, shared decision-making,” Dr. Farber stated in presenting the results at the annual scientific sessions of the American Heart Association.
The study pursued two hypotheses, which is why CLTI patients were divided into two cohorts. For cohort 1, which was limited to CLTI patients with an available saphenous vein, it was predicted that surgery would be better than an endovascular approach. For cohort 2, which enrolled patients who needed an alternative conduit, the hypothesis was that endovascular procedures would prove superior.
The study confirmed the first hypothesis, but there was no difference between the two approaches for the composite primary outcome of major adverse limb events (MALE) in the second cohort.
Saphenous vein availability determined cohort
Candidates for the BEST-CLI (Best Endovascular versus Best Surgical Therapy in Patients with CLTI) trial had to have CLTI producing severe ischemia and to be judged by both surgeons and cardiovascular specialists to be candidates for both types of interventions. Eligible patients were then enrolled in cohort 1 if the saphenous vein was considered the best conduit on imaging. If not, they were enrolled in cohort 2.
Patients were randomized to undergo surgical or endovascular repair only after the cohort was assigned. The primary composite MALE endpoint consisted of an adjudicated first major reintervention, such as new bypass or thrombectomy, an above-the-ankle amputation, or death from any cause.
In cohort 1, the primary composite MALE endpoint was reached in 42.6% of those in surgical arm and 57.4% in the endovascular arm, translating into a 32% relative risk reduction (hazard ratio, 0.68; P < .001) in favor of surgery at the end of a median of 2.7 years of follow-up.
The main advantage was the difference in reinterventions. The lower rate in the surgical group (9.2% vs. 23.5%), translated into a 65% relative risk reduction for this endpoint (HR, 035; P < .001).
The reduction in above-ankle amputations in the surgical group (10.4% vs. 14.9%) was also significant (HR, 0.73; P = .04), but the reduction in all-cause mortality (33.0% vs. 37.6%) was not (HR, 0.98; P = .81).
BEST-CLI involved 150 sites in North America, Europe, and New Zealand. Cohort 1, which randomized 1,434 patients, was the larger of the two. In the second cohort, only 396 patients were randomized, which Dr. Farber said “might have been underpowered.”
The results were published in the New England Journal of Medicine simultaneously with presentation of the results at the meeting.
After a median follow-up of 1.6 years in cohort 2, the slightly lower proportion of patients who reached the composite MALE endpoint in the surgical group relative to the endovascular group (42.8% vs. 47.7%) did not translate into a significant advantage (HR, 0.79; P = .12).
For the individual components, the lower rate of reinterventions in the surgical arm (14.4% vs. 25.6%) did reach statistical significance (HR, 0.47; P = .002), but both amputation (14.9% vs. 14.1%) and all-cause death (26.3% vs. 24.1%) were numerically but not significantly higher in the surgical group.
The primary safety endpoint was major adverse cardiovascular events (MACE). This was not significantly different in either cohort. There were also no major differences between groups in the risk of perioperative complications.
Level 1 evidence provided for intervention choice
Overall, BEST-CLI showed that both surgical and endovascular revascularizations are effective and safe, according to Dr. Farber. As a result, he suggested that both can be considered even if a saphenous vein is available when specific patient characteristics make one more attractive than another.
Yet, in a general population with an available saphenous vein, these data provide “level 1 evidence” that a surgical approach should be the dominant choice, he added.
A quality of life (QOL) substudy of BEST-CLI did not challenge this conclusion. Rather, the main finding was that restoring circulation by either approach has a major favorable impact on patient well-being, according to Matthew Menard, MD, codirector of endovascular surgery at Brigham and Women’s Hospital, Boston.
In this substudy, presented separately from the primary BEST-CLI results, that analysis confirmed that baseline QOL was extremely poor, whether measured with a disease specific instrument such as VascuQol, or generic instruments, such as SF-12.
Surgical or endovascular treatment produced clinically meaningful and sustained improvements in every QOL measure employed, according to Dr. Menard, and this was true in either cohort.
Results not necessarily relevant to all
These data are likely relevant to the patients evaluated, but “it is important to consider who made it into this trial,” according to Naomi M. Hamburg, MD, section chief of vascular biology at Boston University.
Not least, patients had to be candidates for either surgical or endovascular repair to get into the study, omitting those patients not deemed by the investigators to be suited for either.
In addition, Dr. Hamburg pointed out that there was a low enrollment of Blacks (20%) and women (28%), two groups for whom CTLI is a common condition.
Lastly, Dr Hamburg questioned whether specific types of anatomy might be better suited to one procedure relative to another, a variable not considered in this study. Reassured by Dr. Farber that this will be explored in subsequent analyses of BEST-CLI data, Dr. Hamburg expressed interest in learning the results.
Dr. Hamburg was among those who spoke about the growing urgency to optimize strategies for early diagnosis and treatment of CTLI. She plugged the PAD National Action Plan as one of the efforts to thwart the coming wave of CTLI expected from the steep climb in the prevalence of diabetes in the United States.
Dr. Farber reported a financial relationship with Sanifit Therapeutics. The study was funded by the National Heart, Lung, and Blood Institute, but received additional support from multiple pharmaceutical companies. Dr. Menard reported a financial relationship with Janssen Pharmaceuticals. Dr. Hamburg reported financial relationships with Acceleron Pharma, Merck, NovoNordisk, and Sanifit.
CHICAGO – In patients with chronic limb-threatening ischemia (CLTI) and a usable saphenous vein segment, a surgical procedure leads to better outcomes than an endovascular approach, according results of the multinational randomized BEST-CLI trial.
In that study, conducted with two cohorts, the advantage of surgery was limited to the group with an available saphenous vein, but in this group the advantage over an endovascular approach was substantial, according to Alik Farber, MD, chief of vascular and endovascular surgery at Boston University.
“Bypass with adequate saphenous vein should be offered as a first-line treatment option for suitable candidates with CLTI as part of fully informed, shared decision-making,” Dr. Farber stated in presenting the results at the annual scientific sessions of the American Heart Association.
The study pursued two hypotheses, which is why CLTI patients were divided into two cohorts. For cohort 1, which was limited to CLTI patients with an available saphenous vein, it was predicted that surgery would be better than an endovascular approach. For cohort 2, which enrolled patients who needed an alternative conduit, the hypothesis was that endovascular procedures would prove superior.
The study confirmed the first hypothesis, but there was no difference between the two approaches for the composite primary outcome of major adverse limb events (MALE) in the second cohort.
Saphenous vein availability determined cohort
Candidates for the BEST-CLI (Best Endovascular versus Best Surgical Therapy in Patients with CLTI) trial had to have CLTI producing severe ischemia and to be judged by both surgeons and cardiovascular specialists to be candidates for both types of interventions. Eligible patients were then enrolled in cohort 1 if the saphenous vein was considered the best conduit on imaging. If not, they were enrolled in cohort 2.
Patients were randomized to undergo surgical or endovascular repair only after the cohort was assigned. The primary composite MALE endpoint consisted of an adjudicated first major reintervention, such as new bypass or thrombectomy, an above-the-ankle amputation, or death from any cause.
In cohort 1, the primary composite MALE endpoint was reached in 42.6% of those in surgical arm and 57.4% in the endovascular arm, translating into a 32% relative risk reduction (hazard ratio, 0.68; P < .001) in favor of surgery at the end of a median of 2.7 years of follow-up.
The main advantage was the difference in reinterventions. The lower rate in the surgical group (9.2% vs. 23.5%), translated into a 65% relative risk reduction for this endpoint (HR, 035; P < .001).
The reduction in above-ankle amputations in the surgical group (10.4% vs. 14.9%) was also significant (HR, 0.73; P = .04), but the reduction in all-cause mortality (33.0% vs. 37.6%) was not (HR, 0.98; P = .81).
BEST-CLI involved 150 sites in North America, Europe, and New Zealand. Cohort 1, which randomized 1,434 patients, was the larger of the two. In the second cohort, only 396 patients were randomized, which Dr. Farber said “might have been underpowered.”
The results were published in the New England Journal of Medicine simultaneously with presentation of the results at the meeting.
After a median follow-up of 1.6 years in cohort 2, the slightly lower proportion of patients who reached the composite MALE endpoint in the surgical group relative to the endovascular group (42.8% vs. 47.7%) did not translate into a significant advantage (HR, 0.79; P = .12).
For the individual components, the lower rate of reinterventions in the surgical arm (14.4% vs. 25.6%) did reach statistical significance (HR, 0.47; P = .002), but both amputation (14.9% vs. 14.1%) and all-cause death (26.3% vs. 24.1%) were numerically but not significantly higher in the surgical group.
The primary safety endpoint was major adverse cardiovascular events (MACE). This was not significantly different in either cohort. There were also no major differences between groups in the risk of perioperative complications.
Level 1 evidence provided for intervention choice
Overall, BEST-CLI showed that both surgical and endovascular revascularizations are effective and safe, according to Dr. Farber. As a result, he suggested that both can be considered even if a saphenous vein is available when specific patient characteristics make one more attractive than another.
Yet, in a general population with an available saphenous vein, these data provide “level 1 evidence” that a surgical approach should be the dominant choice, he added.
A quality of life (QOL) substudy of BEST-CLI did not challenge this conclusion. Rather, the main finding was that restoring circulation by either approach has a major favorable impact on patient well-being, according to Matthew Menard, MD, codirector of endovascular surgery at Brigham and Women’s Hospital, Boston.
In this substudy, presented separately from the primary BEST-CLI results, that analysis confirmed that baseline QOL was extremely poor, whether measured with a disease specific instrument such as VascuQol, or generic instruments, such as SF-12.
Surgical or endovascular treatment produced clinically meaningful and sustained improvements in every QOL measure employed, according to Dr. Menard, and this was true in either cohort.
Results not necessarily relevant to all
These data are likely relevant to the patients evaluated, but “it is important to consider who made it into this trial,” according to Naomi M. Hamburg, MD, section chief of vascular biology at Boston University.
Not least, patients had to be candidates for either surgical or endovascular repair to get into the study, omitting those patients not deemed by the investigators to be suited for either.
In addition, Dr. Hamburg pointed out that there was a low enrollment of Blacks (20%) and women (28%), two groups for whom CTLI is a common condition.
Lastly, Dr Hamburg questioned whether specific types of anatomy might be better suited to one procedure relative to another, a variable not considered in this study. Reassured by Dr. Farber that this will be explored in subsequent analyses of BEST-CLI data, Dr. Hamburg expressed interest in learning the results.
Dr. Hamburg was among those who spoke about the growing urgency to optimize strategies for early diagnosis and treatment of CTLI. She plugged the PAD National Action Plan as one of the efforts to thwart the coming wave of CTLI expected from the steep climb in the prevalence of diabetes in the United States.
Dr. Farber reported a financial relationship with Sanifit Therapeutics. The study was funded by the National Heart, Lung, and Blood Institute, but received additional support from multiple pharmaceutical companies. Dr. Menard reported a financial relationship with Janssen Pharmaceuticals. Dr. Hamburg reported financial relationships with Acceleron Pharma, Merck, NovoNordisk, and Sanifit.
AT AHA 2022
AHA pens roadmap to more patient-focused care for PAD
Patient-reported symptoms and quality of life should guide treatment for the roughly 8.5 million people in the United States living with peripheral artery disease (PAD), the American Heart Association said in a new scientific statement released Oct. 13.
“The person living with PAD is the authority on the impact it has on their daily life. Our treatment must be grounded in their lived experiences and go beyond the clinical measures of how well blood flows through the arteries,” Kim G. Smolderen, PhD, lead author of the statement writing group, says in a release.
“We have spent years developing and validating standardized instruments to capture people’s experiences in a reliable and sensitive way. We are now at a point where we can start integrating this information into real-world care, through pilot programs that can develop quality benchmarks for different phenotypes of patients with PAD and the types of treatments they undergo, as seen from their perspective,” adds Dr. Smolderen, co-director of the Vascular Medicine Outcomes Research (VAMOS) lab at Yale University, New Haven, Conn.
The statement, “Advancing Peripheral Artery Disease Quality of Care and Outcomes Through Patient-Reported Health Status Assessment,” is published online in Circulation.
It comes on the heels of a 2021 AHA statement urging greater attention to PAD, which is underdiagnosed and undertreated in the United States despite its high prevalence.
Fragmented care
Dr. Smolderen said that the multidisciplinary writing group was united in one overarching goal: “How can we disrupt the fragmented care model for PAD and make PAD care more accountable, value-based, and patient-centered?”
“True disruption is needed in a clinical space where the treatment of lower-extremity disease lies in the hands of many different specialties and variability in care and outcomes is a major concern,” Dr. Smolderen said.
The statement calls for improving and individualizing PAD care by gathering feedback from their experience through treatment using systematic and validated patient-reported outcome measures (PROMs).
PROMs for PAD include the Walking Impairment Questionnaire (WIQ), the Vascular Quality of Life Questionnaire (VascuQoL), and Peripheral Artery Questionnaire (PAQ).
Accountability tied to reimbursement
Dr. Smolderen noted that PROMs are increasingly being integrated into definitions of what it means to deliver high-quality, patient-centered care, and PROMs scores may directly impact reimbursement.
“Using a template that has been implemented in other medical conditions, we propose a shift in metrics that will tell us whether high-quality PAD care has been delivered from a patients’ perspective,” Dr. Smolderen told this news organization.
That is, “have we been able to improve the health status of that person’s life? We may have removed the blockage in the arteries, but will the patient feel that this intervention has addressed their PAD-specific health status goals?”
To facilitate accountability in quality PAD care, the writing group calls for developing, testing, and implementing PAD-specific patient-reported outcomes performance measures – or PRO-PMs.
Pilot efforts demonstrating feasibility of PRO-PMs in various practice settings are needed, as is implementation research evaluating the integration of PRO-PMs and pragmatic clinical trial evidence to demonstrate efficacy of the use of PROs in real world care settings to improve overall PAD outcomes, the writing group says.
“Following that experience and data, we believe value-based models can be proposed integrating PRO information that will affect accountability in PAD care and may ultimately affect reimbursement,” Dr. Smolderen said.
“Adoption of this new paradigm will further improve the quality of care for PAD and will put the patient front and center, as an agent in their care,” she added.
This scientific statement was prepared by the volunteer writing group on behalf of the AHA Council on Peripheral Vascular Disease and the Council on Lifestyle and Cardiometabolic Health. The writing group includes a patient advocate and experts in clinical psychology, outcomes research, nursing, cardiology, vascular surgery, and vascular medicine.
This research had no commercial funding. Dr. Smolderen has disclosed relationships with Optum, Abbott, Cook Medical, Happify, and Tegus.
A version of this article first appeared on Medscape.com.
Patient-reported symptoms and quality of life should guide treatment for the roughly 8.5 million people in the United States living with peripheral artery disease (PAD), the American Heart Association said in a new scientific statement released Oct. 13.
“The person living with PAD is the authority on the impact it has on their daily life. Our treatment must be grounded in their lived experiences and go beyond the clinical measures of how well blood flows through the arteries,” Kim G. Smolderen, PhD, lead author of the statement writing group, says in a release.
“We have spent years developing and validating standardized instruments to capture people’s experiences in a reliable and sensitive way. We are now at a point where we can start integrating this information into real-world care, through pilot programs that can develop quality benchmarks for different phenotypes of patients with PAD and the types of treatments they undergo, as seen from their perspective,” adds Dr. Smolderen, co-director of the Vascular Medicine Outcomes Research (VAMOS) lab at Yale University, New Haven, Conn.
The statement, “Advancing Peripheral Artery Disease Quality of Care and Outcomes Through Patient-Reported Health Status Assessment,” is published online in Circulation.
It comes on the heels of a 2021 AHA statement urging greater attention to PAD, which is underdiagnosed and undertreated in the United States despite its high prevalence.
Fragmented care
Dr. Smolderen said that the multidisciplinary writing group was united in one overarching goal: “How can we disrupt the fragmented care model for PAD and make PAD care more accountable, value-based, and patient-centered?”
“True disruption is needed in a clinical space where the treatment of lower-extremity disease lies in the hands of many different specialties and variability in care and outcomes is a major concern,” Dr. Smolderen said.
The statement calls for improving and individualizing PAD care by gathering feedback from their experience through treatment using systematic and validated patient-reported outcome measures (PROMs).
PROMs for PAD include the Walking Impairment Questionnaire (WIQ), the Vascular Quality of Life Questionnaire (VascuQoL), and Peripheral Artery Questionnaire (PAQ).
Accountability tied to reimbursement
Dr. Smolderen noted that PROMs are increasingly being integrated into definitions of what it means to deliver high-quality, patient-centered care, and PROMs scores may directly impact reimbursement.
“Using a template that has been implemented in other medical conditions, we propose a shift in metrics that will tell us whether high-quality PAD care has been delivered from a patients’ perspective,” Dr. Smolderen told this news organization.
That is, “have we been able to improve the health status of that person’s life? We may have removed the blockage in the arteries, but will the patient feel that this intervention has addressed their PAD-specific health status goals?”
To facilitate accountability in quality PAD care, the writing group calls for developing, testing, and implementing PAD-specific patient-reported outcomes performance measures – or PRO-PMs.
Pilot efforts demonstrating feasibility of PRO-PMs in various practice settings are needed, as is implementation research evaluating the integration of PRO-PMs and pragmatic clinical trial evidence to demonstrate efficacy of the use of PROs in real world care settings to improve overall PAD outcomes, the writing group says.
“Following that experience and data, we believe value-based models can be proposed integrating PRO information that will affect accountability in PAD care and may ultimately affect reimbursement,” Dr. Smolderen said.
“Adoption of this new paradigm will further improve the quality of care for PAD and will put the patient front and center, as an agent in their care,” she added.
This scientific statement was prepared by the volunteer writing group on behalf of the AHA Council on Peripheral Vascular Disease and the Council on Lifestyle and Cardiometabolic Health. The writing group includes a patient advocate and experts in clinical psychology, outcomes research, nursing, cardiology, vascular surgery, and vascular medicine.
This research had no commercial funding. Dr. Smolderen has disclosed relationships with Optum, Abbott, Cook Medical, Happify, and Tegus.
A version of this article first appeared on Medscape.com.
Patient-reported symptoms and quality of life should guide treatment for the roughly 8.5 million people in the United States living with peripheral artery disease (PAD), the American Heart Association said in a new scientific statement released Oct. 13.
“The person living with PAD is the authority on the impact it has on their daily life. Our treatment must be grounded in their lived experiences and go beyond the clinical measures of how well blood flows through the arteries,” Kim G. Smolderen, PhD, lead author of the statement writing group, says in a release.
“We have spent years developing and validating standardized instruments to capture people’s experiences in a reliable and sensitive way. We are now at a point where we can start integrating this information into real-world care, through pilot programs that can develop quality benchmarks for different phenotypes of patients with PAD and the types of treatments they undergo, as seen from their perspective,” adds Dr. Smolderen, co-director of the Vascular Medicine Outcomes Research (VAMOS) lab at Yale University, New Haven, Conn.
The statement, “Advancing Peripheral Artery Disease Quality of Care and Outcomes Through Patient-Reported Health Status Assessment,” is published online in Circulation.
It comes on the heels of a 2021 AHA statement urging greater attention to PAD, which is underdiagnosed and undertreated in the United States despite its high prevalence.
Fragmented care
Dr. Smolderen said that the multidisciplinary writing group was united in one overarching goal: “How can we disrupt the fragmented care model for PAD and make PAD care more accountable, value-based, and patient-centered?”
“True disruption is needed in a clinical space where the treatment of lower-extremity disease lies in the hands of many different specialties and variability in care and outcomes is a major concern,” Dr. Smolderen said.
The statement calls for improving and individualizing PAD care by gathering feedback from their experience through treatment using systematic and validated patient-reported outcome measures (PROMs).
PROMs for PAD include the Walking Impairment Questionnaire (WIQ), the Vascular Quality of Life Questionnaire (VascuQoL), and Peripheral Artery Questionnaire (PAQ).
Accountability tied to reimbursement
Dr. Smolderen noted that PROMs are increasingly being integrated into definitions of what it means to deliver high-quality, patient-centered care, and PROMs scores may directly impact reimbursement.
“Using a template that has been implemented in other medical conditions, we propose a shift in metrics that will tell us whether high-quality PAD care has been delivered from a patients’ perspective,” Dr. Smolderen told this news organization.
That is, “have we been able to improve the health status of that person’s life? We may have removed the blockage in the arteries, but will the patient feel that this intervention has addressed their PAD-specific health status goals?”
To facilitate accountability in quality PAD care, the writing group calls for developing, testing, and implementing PAD-specific patient-reported outcomes performance measures – or PRO-PMs.
Pilot efforts demonstrating feasibility of PRO-PMs in various practice settings are needed, as is implementation research evaluating the integration of PRO-PMs and pragmatic clinical trial evidence to demonstrate efficacy of the use of PROs in real world care settings to improve overall PAD outcomes, the writing group says.
“Following that experience and data, we believe value-based models can be proposed integrating PRO information that will affect accountability in PAD care and may ultimately affect reimbursement,” Dr. Smolderen said.
“Adoption of this new paradigm will further improve the quality of care for PAD and will put the patient front and center, as an agent in their care,” she added.
This scientific statement was prepared by the volunteer writing group on behalf of the AHA Council on Peripheral Vascular Disease and the Council on Lifestyle and Cardiometabolic Health. The writing group includes a patient advocate and experts in clinical psychology, outcomes research, nursing, cardiology, vascular surgery, and vascular medicine.
This research had no commercial funding. Dr. Smolderen has disclosed relationships with Optum, Abbott, Cook Medical, Happify, and Tegus.
A version of this article first appeared on Medscape.com.
FROM CIRCULATION
‘Amazing’ data for cheap beta-blocker gel for diabetic foot ulcers
STOCKHOLM – Esmolol hydrochloride gel (Galnobax, NovoLead) appears to be a safe and effective novel topical treatment option for diabetic foot ulcers, according to results from a new trial of the drug, which is widely available as a generic and is inexpensive.
Of note, the proportion of participants achieving target ulcer closure at 12 weeks with esmolol (plus standard of care) was around 60% compared with just over 40% in patients who received standard of care alone.
Presenting the findings at this year’s annual meeting of the European Association for the Study of Diabetes was Ashu Rastogi, MD, a professor of endocrinology at the Postgraduate Institute of Medical Education and Research in Chandigarh, India.
“Esmolol can be given topically as a 14% gel and is a novel treatment option in diabetic foot ulcer,” said Dr. Rastogi.
Esmolol, a short-acting beta-adrenergic blocker, is currently approved by the U.S. Food and Drug Administration for cardiac indications only, such as short-term use for controlling supraventricular tachycardia. Beta-blockers are also used to treat hypertension.
However, esmolol has also been repurposed and formulated as a topical gel for the treatment of hard-to-heal diabetic foot ulcers (mainly neuropathic grade 1).
Audience member Ketan Dhatariya, MBBS, MD, PhD, a National Health Service consultant in diabetes, endocrinology, and general medicine and honorary senior lecturer at Norfolk and Norwich University Hospitals, England, enthused about the findings.
“This is an amazing study. I’m part of a working group looking at the updating of a guideline for the International Working Group of the Diabetic Foot, reviewing all the studies on wound healing, specifically pharmacological interventions. This is way beyond anything shown to date in terms of medical intervention. [The authors] should be congratulated; this is really astounding,” he told this news organization.
“Right now, there is very little out there in terms of pharmacological interventions that have shown benefit,” he added. “Once this study has been peer-reviewed and is published properly, it is potentially game-changing because it is a generic, worldwide, cheap, and freely available medication.”
Study across 27 sites in India
Prior phase 1/2 data have shown that 60% of ulcers completely closed with esmolol (14% gel) compared with 39% with standard of care. Encouraged by these findings, a phase 3 randomized, double-blind placebo-controlled study was conducted across 27 sites in India.
Patients were a mean age of 56 years, and had a body mass index (BMI) of 25-26 kg/m2 and mean hemoglobin A1c of 8.4%-8.7%. Around 70% of participants were men. Mean ulcer area was approximately 460-500 mm2, two-thirds of the ulcers were plantar, and mean ulcer duration was 40-50 weeks.
After screening and discontinuations (39 participants), a 12-week treatment phase began with patients randomized to one of three groups: esmolol (14% gel) along with standard of care administered twice daily (57 completers); standard of care only (63 completers); or vehicle gel (placebo) along with standard of care administered twice daily (17 completers).
Standard of care comprised wound cleaning, debridement, maintenance of moist wound environment, twice-daily fresh bandages, and off-loading footwear as needed, and was provided to all participants irrespective of study group.
The 12-week treatment period was followed by an observation period of 12 weeks up to the 24-week study endpoint.
The primary efficacy endpoint was the proportion of participants achieving target ulcer closure (100% re-epithelialization without drainage or dressing requirement) within the 12-week treatment phase.
Secondary endpoints included time to target ulcer closure during the 12-week treatment phase and proportion of participants achieving target ulcer closure by 24 weeks (end of study). Investigators were blinded throughout.
Subanalyses were conducted based on ulcer location, size, and age, as well as estimated glomerular filtration rate less than 90 mL/min and ankle-brachial index under 0.9 but greater than 0.7.
50% more patients on esmolol had complete ulcer closure
The proportion of participants with complete ulcer closure at 12 weeks was 60.3% in the esmolol plus standard of care group, compared with 41.7% with standard of care only, a difference of 18.6% (odds ratio, 2.13; P = .0276).
“The 24-week end-of-study data show what happened in the 12 weeks following end of treatment,” said Dr. Rastogi, turning to results showing that by 24 weeks the proportion of participants with complete ulcer closure was 77.2% versus 55.6%, respectively, with a difference of 21.6% (OR, 2.71; P = .013).
Time to ulcer closure (a secondary endpoint) was similar between the esmolol plus standard of care vs. standard of care groups (74.3 vs. 72.5 days).
The impact of ulcer location on complete ulcer closure, a subanalysis, showed a higher proportion of patients experienced complete ulcer closure with esmolol plus standard of care versus standard of care. For example, in plantar-based ulcers, esmolol led to complete closure in 58.7% vs. 43.1%, while for nonplantar ulcers, complete closure was found in 63.6% vs. 38.1%.
In wounds less than 5 cm2, the proportion of complete closures was 66.0% vs. 50.0% for esmolol compared with standard of care alone, while in wounds over 5 cm2, these proportions were 47.6% vs. 26.9%.
Subanalyses also showed that esmolol was substantially better in patients with BMI greater than 25, ulcer duration over 12 weeks, and A1c above 8%.
Also, a subanalysis stratified by “real-life” situations favored esmolol, showing a 50.9% difference in the proportion of patients with diabetic foot ulcer healing in those with a history of hypertension and a 31.8% difference favoring esmolol in those with an abnormal electrocardiogram.
Overall, the proportions of patients who had an adverse event were 13.2%, 18.4%, and 37.5% in the esmolol plus standard of care, standard of care alone, and vehicle plus standard of care groups, respectively, and the vast majority were unrelated to study drug. There were no serious adverse events in the esmolol plus standard of care group.
A class effect of beta blockers?
The proposed mechanism of action of esmolol relates to a sequence of reducing inflammation (via vasodilation, fibroblast migration, and cytokine reduction); proliferation by beta-blockade (improves keratinocyte migration and epithelialization); and remodeling (increases collagen turnover).
Asked by an audience member if the observations were a class effect and systemic effect of beta-blockers, Dr. Rastogi said he could not say for sure that it was a class effect, but they deliberately used a beta-1 adrenergic receptor antagonist.
“It may not be a systemic effect because we have some patients who use beta-blockers systemically and they still have diabetic foot ulcers,” he said.
Dr. Rastogi and Dr. Dhatariya have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
STOCKHOLM – Esmolol hydrochloride gel (Galnobax, NovoLead) appears to be a safe and effective novel topical treatment option for diabetic foot ulcers, according to results from a new trial of the drug, which is widely available as a generic and is inexpensive.
Of note, the proportion of participants achieving target ulcer closure at 12 weeks with esmolol (plus standard of care) was around 60% compared with just over 40% in patients who received standard of care alone.
Presenting the findings at this year’s annual meeting of the European Association for the Study of Diabetes was Ashu Rastogi, MD, a professor of endocrinology at the Postgraduate Institute of Medical Education and Research in Chandigarh, India.
“Esmolol can be given topically as a 14% gel and is a novel treatment option in diabetic foot ulcer,” said Dr. Rastogi.
Esmolol, a short-acting beta-adrenergic blocker, is currently approved by the U.S. Food and Drug Administration for cardiac indications only, such as short-term use for controlling supraventricular tachycardia. Beta-blockers are also used to treat hypertension.
However, esmolol has also been repurposed and formulated as a topical gel for the treatment of hard-to-heal diabetic foot ulcers (mainly neuropathic grade 1).
Audience member Ketan Dhatariya, MBBS, MD, PhD, a National Health Service consultant in diabetes, endocrinology, and general medicine and honorary senior lecturer at Norfolk and Norwich University Hospitals, England, enthused about the findings.
“This is an amazing study. I’m part of a working group looking at the updating of a guideline for the International Working Group of the Diabetic Foot, reviewing all the studies on wound healing, specifically pharmacological interventions. This is way beyond anything shown to date in terms of medical intervention. [The authors] should be congratulated; this is really astounding,” he told this news organization.
“Right now, there is very little out there in terms of pharmacological interventions that have shown benefit,” he added. “Once this study has been peer-reviewed and is published properly, it is potentially game-changing because it is a generic, worldwide, cheap, and freely available medication.”
Study across 27 sites in India
Prior phase 1/2 data have shown that 60% of ulcers completely closed with esmolol (14% gel) compared with 39% with standard of care. Encouraged by these findings, a phase 3 randomized, double-blind placebo-controlled study was conducted across 27 sites in India.
Patients were a mean age of 56 years, and had a body mass index (BMI) of 25-26 kg/m2 and mean hemoglobin A1c of 8.4%-8.7%. Around 70% of participants were men. Mean ulcer area was approximately 460-500 mm2, two-thirds of the ulcers were plantar, and mean ulcer duration was 40-50 weeks.
After screening and discontinuations (39 participants), a 12-week treatment phase began with patients randomized to one of three groups: esmolol (14% gel) along with standard of care administered twice daily (57 completers); standard of care only (63 completers); or vehicle gel (placebo) along with standard of care administered twice daily (17 completers).
Standard of care comprised wound cleaning, debridement, maintenance of moist wound environment, twice-daily fresh bandages, and off-loading footwear as needed, and was provided to all participants irrespective of study group.
The 12-week treatment period was followed by an observation period of 12 weeks up to the 24-week study endpoint.
The primary efficacy endpoint was the proportion of participants achieving target ulcer closure (100% re-epithelialization without drainage or dressing requirement) within the 12-week treatment phase.
Secondary endpoints included time to target ulcer closure during the 12-week treatment phase and proportion of participants achieving target ulcer closure by 24 weeks (end of study). Investigators were blinded throughout.
Subanalyses were conducted based on ulcer location, size, and age, as well as estimated glomerular filtration rate less than 90 mL/min and ankle-brachial index under 0.9 but greater than 0.7.
50% more patients on esmolol had complete ulcer closure
The proportion of participants with complete ulcer closure at 12 weeks was 60.3% in the esmolol plus standard of care group, compared with 41.7% with standard of care only, a difference of 18.6% (odds ratio, 2.13; P = .0276).
“The 24-week end-of-study data show what happened in the 12 weeks following end of treatment,” said Dr. Rastogi, turning to results showing that by 24 weeks the proportion of participants with complete ulcer closure was 77.2% versus 55.6%, respectively, with a difference of 21.6% (OR, 2.71; P = .013).
Time to ulcer closure (a secondary endpoint) was similar between the esmolol plus standard of care vs. standard of care groups (74.3 vs. 72.5 days).
The impact of ulcer location on complete ulcer closure, a subanalysis, showed a higher proportion of patients experienced complete ulcer closure with esmolol plus standard of care versus standard of care. For example, in plantar-based ulcers, esmolol led to complete closure in 58.7% vs. 43.1%, while for nonplantar ulcers, complete closure was found in 63.6% vs. 38.1%.
In wounds less than 5 cm2, the proportion of complete closures was 66.0% vs. 50.0% for esmolol compared with standard of care alone, while in wounds over 5 cm2, these proportions were 47.6% vs. 26.9%.
Subanalyses also showed that esmolol was substantially better in patients with BMI greater than 25, ulcer duration over 12 weeks, and A1c above 8%.
Also, a subanalysis stratified by “real-life” situations favored esmolol, showing a 50.9% difference in the proportion of patients with diabetic foot ulcer healing in those with a history of hypertension and a 31.8% difference favoring esmolol in those with an abnormal electrocardiogram.
Overall, the proportions of patients who had an adverse event were 13.2%, 18.4%, and 37.5% in the esmolol plus standard of care, standard of care alone, and vehicle plus standard of care groups, respectively, and the vast majority were unrelated to study drug. There were no serious adverse events in the esmolol plus standard of care group.
A class effect of beta blockers?
The proposed mechanism of action of esmolol relates to a sequence of reducing inflammation (via vasodilation, fibroblast migration, and cytokine reduction); proliferation by beta-blockade (improves keratinocyte migration and epithelialization); and remodeling (increases collagen turnover).
Asked by an audience member if the observations were a class effect and systemic effect of beta-blockers, Dr. Rastogi said he could not say for sure that it was a class effect, but they deliberately used a beta-1 adrenergic receptor antagonist.
“It may not be a systemic effect because we have some patients who use beta-blockers systemically and they still have diabetic foot ulcers,” he said.
Dr. Rastogi and Dr. Dhatariya have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
STOCKHOLM – Esmolol hydrochloride gel (Galnobax, NovoLead) appears to be a safe and effective novel topical treatment option for diabetic foot ulcers, according to results from a new trial of the drug, which is widely available as a generic and is inexpensive.
Of note, the proportion of participants achieving target ulcer closure at 12 weeks with esmolol (plus standard of care) was around 60% compared with just over 40% in patients who received standard of care alone.
Presenting the findings at this year’s annual meeting of the European Association for the Study of Diabetes was Ashu Rastogi, MD, a professor of endocrinology at the Postgraduate Institute of Medical Education and Research in Chandigarh, India.
“Esmolol can be given topically as a 14% gel and is a novel treatment option in diabetic foot ulcer,” said Dr. Rastogi.
Esmolol, a short-acting beta-adrenergic blocker, is currently approved by the U.S. Food and Drug Administration for cardiac indications only, such as short-term use for controlling supraventricular tachycardia. Beta-blockers are also used to treat hypertension.
However, esmolol has also been repurposed and formulated as a topical gel for the treatment of hard-to-heal diabetic foot ulcers (mainly neuropathic grade 1).
Audience member Ketan Dhatariya, MBBS, MD, PhD, a National Health Service consultant in diabetes, endocrinology, and general medicine and honorary senior lecturer at Norfolk and Norwich University Hospitals, England, enthused about the findings.
“This is an amazing study. I’m part of a working group looking at the updating of a guideline for the International Working Group of the Diabetic Foot, reviewing all the studies on wound healing, specifically pharmacological interventions. This is way beyond anything shown to date in terms of medical intervention. [The authors] should be congratulated; this is really astounding,” he told this news organization.
“Right now, there is very little out there in terms of pharmacological interventions that have shown benefit,” he added. “Once this study has been peer-reviewed and is published properly, it is potentially game-changing because it is a generic, worldwide, cheap, and freely available medication.”
Study across 27 sites in India
Prior phase 1/2 data have shown that 60% of ulcers completely closed with esmolol (14% gel) compared with 39% with standard of care. Encouraged by these findings, a phase 3 randomized, double-blind placebo-controlled study was conducted across 27 sites in India.
Patients were a mean age of 56 years, and had a body mass index (BMI) of 25-26 kg/m2 and mean hemoglobin A1c of 8.4%-8.7%. Around 70% of participants were men. Mean ulcer area was approximately 460-500 mm2, two-thirds of the ulcers were plantar, and mean ulcer duration was 40-50 weeks.
After screening and discontinuations (39 participants), a 12-week treatment phase began with patients randomized to one of three groups: esmolol (14% gel) along with standard of care administered twice daily (57 completers); standard of care only (63 completers); or vehicle gel (placebo) along with standard of care administered twice daily (17 completers).
Standard of care comprised wound cleaning, debridement, maintenance of moist wound environment, twice-daily fresh bandages, and off-loading footwear as needed, and was provided to all participants irrespective of study group.
The 12-week treatment period was followed by an observation period of 12 weeks up to the 24-week study endpoint.
The primary efficacy endpoint was the proportion of participants achieving target ulcer closure (100% re-epithelialization without drainage or dressing requirement) within the 12-week treatment phase.
Secondary endpoints included time to target ulcer closure during the 12-week treatment phase and proportion of participants achieving target ulcer closure by 24 weeks (end of study). Investigators were blinded throughout.
Subanalyses were conducted based on ulcer location, size, and age, as well as estimated glomerular filtration rate less than 90 mL/min and ankle-brachial index under 0.9 but greater than 0.7.
50% more patients on esmolol had complete ulcer closure
The proportion of participants with complete ulcer closure at 12 weeks was 60.3% in the esmolol plus standard of care group, compared with 41.7% with standard of care only, a difference of 18.6% (odds ratio, 2.13; P = .0276).
“The 24-week end-of-study data show what happened in the 12 weeks following end of treatment,” said Dr. Rastogi, turning to results showing that by 24 weeks the proportion of participants with complete ulcer closure was 77.2% versus 55.6%, respectively, with a difference of 21.6% (OR, 2.71; P = .013).
Time to ulcer closure (a secondary endpoint) was similar between the esmolol plus standard of care vs. standard of care groups (74.3 vs. 72.5 days).
The impact of ulcer location on complete ulcer closure, a subanalysis, showed a higher proportion of patients experienced complete ulcer closure with esmolol plus standard of care versus standard of care. For example, in plantar-based ulcers, esmolol led to complete closure in 58.7% vs. 43.1%, while for nonplantar ulcers, complete closure was found in 63.6% vs. 38.1%.
In wounds less than 5 cm2, the proportion of complete closures was 66.0% vs. 50.0% for esmolol compared with standard of care alone, while in wounds over 5 cm2, these proportions were 47.6% vs. 26.9%.
Subanalyses also showed that esmolol was substantially better in patients with BMI greater than 25, ulcer duration over 12 weeks, and A1c above 8%.
Also, a subanalysis stratified by “real-life” situations favored esmolol, showing a 50.9% difference in the proportion of patients with diabetic foot ulcer healing in those with a history of hypertension and a 31.8% difference favoring esmolol in those with an abnormal electrocardiogram.
Overall, the proportions of patients who had an adverse event were 13.2%, 18.4%, and 37.5% in the esmolol plus standard of care, standard of care alone, and vehicle plus standard of care groups, respectively, and the vast majority were unrelated to study drug. There were no serious adverse events in the esmolol plus standard of care group.
A class effect of beta blockers?
The proposed mechanism of action of esmolol relates to a sequence of reducing inflammation (via vasodilation, fibroblast migration, and cytokine reduction); proliferation by beta-blockade (improves keratinocyte migration and epithelialization); and remodeling (increases collagen turnover).
Asked by an audience member if the observations were a class effect and systemic effect of beta-blockers, Dr. Rastogi said he could not say for sure that it was a class effect, but they deliberately used a beta-1 adrenergic receptor antagonist.
“It may not be a systemic effect because we have some patients who use beta-blockers systemically and they still have diabetic foot ulcers,” he said.
Dr. Rastogi and Dr. Dhatariya have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM EASD 2022
ARBs, beta-blockers independently inhibit Marfan syndrome progression
Early start might delay surgery
Beta-blockers have long been recommended to prevent aortic dissection associated with Marfan syndrome despite limited evidence, but a new analysis also supports a benefit from angiotensin receptors blockers (ARBs) and further suggests that beta-blockers and ARBs exert independent effects.
For the endpoint of inhibition of growth of the aortic root, “there is no evidence of any interaction between the effects of ARBs with beta-blockers, and so we think that the treatment effects are likely to be additive,” reported Alex Pitcher, BMBCh, DPhil, Oxford (England) University Hospitals, NHS Trust.
Based on these data, Dr. Pitcher recommended considering ARBs and beta-blockers together soon after the diagnosis of Marfan syndrome. This includes young children.
“We think that medical treatments can delay surgery and dissection substantially if given for a number of years,” he added.
In this study, undertaken by the Marfan Treatment Trialists (MTT) collaboration, data were available from 1,442 Marfan syndrome patients participating in seven treatment trials. The primary outcome was aortic root enlargement, a predictor of life-threatening aortic dissection and rupture. Rather than a meta-analysis of the pooled data, the meta-analysis was conducted with individual patient data that involved collaboration with the original trialists.
Four of the studies with 746 patients compared ARBs to placebo or a control medication. A second group of three trials with 766 patients compared ARBs to beta-blockers.
From the two sets of data, a calculation of the effect of beta-blockers was indirectly estimated.
ARBs slow annualized aortic growth rate significantly
In the first set of trials, the analysis showed a significantly slower annualized aortic root growth rate for those treated with ARBs relative to controls (0.07 vs. 0.13), producing a statistically significant absolute difference (0.7%; P = .01) in favor of the ARB.
“In other words, the rate of growth was nearly double in the control arm,” Dr. Pitcher said.
In the three trials comparing ARBs to beta-blockers, the annualized growth rate among those taking an ARB was similar (0.8%) to that seen in the previous set of controlled trials. This rate of annualized growth was not significantly different from the 0.11% annualized rate of growth in patients receiving beta-blockers. When an analysis of the impact of beta-blockers was conducted by indirectly evaluating the change in growth relative to controls, the estimated impact was an annualized growth rate of 0.9% (P = .042).
A second set of data provided the basis for suggesting that the effects of beta ARBs and beta-blockers are independent and potentially additive.
“We were able to look at subgroups of patients in the ARB trials that were broken down by whether they were or were not on beta-blockers at baseline, and so by doing able to estimate independent effects,” Dr. Pitcher said. The lack of any interactions led Dr. Pitcher to conclude that benefits are likely additive.
Of patients genotyped in the ARB studies, more than 80% had the FBN1 pathogenic variant of Marfan syndrome. When the data were analyzed by subgroups, including age or blood pressure, there were no differences in treatment effect except for those with the FBN1 mutation in whom the benefit of ARB therapy was greater relative to those without.
As FBN1 is one of the most common genetic signatures of Marfan syndrome, the “greater effect of ARBs in this group makes it more plausible that the effect is real,” Dr. Pitcher said.
Results could change treatment guidelines
Current guidelines recommend beta-blockers in Marfan syndrome prior to a dilatation size of 4.5 to 5 cm when surgery is indicated, according to Dr. Pitcher, but he said these data might change guidelines. While reinforcing the benefit of beta-blockers, this analysis suggests ARBs should also be considered, possibly in combination with beta-blockers.
“What I hope this meta-analysis does is add substantially to the certainty with which physicians can discuss treatments with patients.”
As for the mechanism, it is reasonable to speculate the antihypertensive effect of both medications is relevant, but each has plausible independent activities that might contribute to modifying aortic growth, according to Roland R.J. van Kimmenade, MD, PhD, a specialist in aortic diseases and heart failure at Raboud University Medical Center, Nijmegan, the Netherlands.
Citing several studies, he suggested that the benefit of beta-blockers could also stem from their ability to reduce heart rate and aortic stiffness while ARBs are likely to inhibit the interaction between the renin-angiotensin system (RAS) and TGF-beta pathway. Each of these might participate in risk of aortic root growth, according to Dr. van Kimmenade, who was invited by ESC to discuss this study.
On the basis of these data as well as past studies, he agreed that the combination of beta-blockers and ARBs might not just be additive but “even a little bit synergistic.”
While Dr. Pitcher suggested that the evidence supports starting both beta-blockers and ARBs soon after the diagnosis, Dr. van Kimmenade said, “I don’t like using beta-blockers in young patients, but ARBs are now shown to be an excellent alternative.”
Ultimately, “the prescription pencil will not replace the surgical knife” in a disease that is likely to eventually require surgery to prevent life-threatening events, according to Dr. van Kimmenade, but he agreed that these data provide more certainty about the value of beta-blockers and ARBs for slowing progression.
Dr. Pitcher reports no potential conflicts of interest. Dr. van Kimmenade has financial relationships with Bayer and Novartis.
Early start might delay surgery
Early start might delay surgery
Beta-blockers have long been recommended to prevent aortic dissection associated with Marfan syndrome despite limited evidence, but a new analysis also supports a benefit from angiotensin receptors blockers (ARBs) and further suggests that beta-blockers and ARBs exert independent effects.
For the endpoint of inhibition of growth of the aortic root, “there is no evidence of any interaction between the effects of ARBs with beta-blockers, and so we think that the treatment effects are likely to be additive,” reported Alex Pitcher, BMBCh, DPhil, Oxford (England) University Hospitals, NHS Trust.
Based on these data, Dr. Pitcher recommended considering ARBs and beta-blockers together soon after the diagnosis of Marfan syndrome. This includes young children.
“We think that medical treatments can delay surgery and dissection substantially if given for a number of years,” he added.
In this study, undertaken by the Marfan Treatment Trialists (MTT) collaboration, data were available from 1,442 Marfan syndrome patients participating in seven treatment trials. The primary outcome was aortic root enlargement, a predictor of life-threatening aortic dissection and rupture. Rather than a meta-analysis of the pooled data, the meta-analysis was conducted with individual patient data that involved collaboration with the original trialists.
Four of the studies with 746 patients compared ARBs to placebo or a control medication. A second group of three trials with 766 patients compared ARBs to beta-blockers.
From the two sets of data, a calculation of the effect of beta-blockers was indirectly estimated.
ARBs slow annualized aortic growth rate significantly
In the first set of trials, the analysis showed a significantly slower annualized aortic root growth rate for those treated with ARBs relative to controls (0.07 vs. 0.13), producing a statistically significant absolute difference (0.7%; P = .01) in favor of the ARB.
“In other words, the rate of growth was nearly double in the control arm,” Dr. Pitcher said.
In the three trials comparing ARBs to beta-blockers, the annualized growth rate among those taking an ARB was similar (0.8%) to that seen in the previous set of controlled trials. This rate of annualized growth was not significantly different from the 0.11% annualized rate of growth in patients receiving beta-blockers. When an analysis of the impact of beta-blockers was conducted by indirectly evaluating the change in growth relative to controls, the estimated impact was an annualized growth rate of 0.9% (P = .042).
A second set of data provided the basis for suggesting that the effects of beta ARBs and beta-blockers are independent and potentially additive.
“We were able to look at subgroups of patients in the ARB trials that were broken down by whether they were or were not on beta-blockers at baseline, and so by doing able to estimate independent effects,” Dr. Pitcher said. The lack of any interactions led Dr. Pitcher to conclude that benefits are likely additive.
Of patients genotyped in the ARB studies, more than 80% had the FBN1 pathogenic variant of Marfan syndrome. When the data were analyzed by subgroups, including age or blood pressure, there were no differences in treatment effect except for those with the FBN1 mutation in whom the benefit of ARB therapy was greater relative to those without.
As FBN1 is one of the most common genetic signatures of Marfan syndrome, the “greater effect of ARBs in this group makes it more plausible that the effect is real,” Dr. Pitcher said.
Results could change treatment guidelines
Current guidelines recommend beta-blockers in Marfan syndrome prior to a dilatation size of 4.5 to 5 cm when surgery is indicated, according to Dr. Pitcher, but he said these data might change guidelines. While reinforcing the benefit of beta-blockers, this analysis suggests ARBs should also be considered, possibly in combination with beta-blockers.
“What I hope this meta-analysis does is add substantially to the certainty with which physicians can discuss treatments with patients.”
As for the mechanism, it is reasonable to speculate the antihypertensive effect of both medications is relevant, but each has plausible independent activities that might contribute to modifying aortic growth, according to Roland R.J. van Kimmenade, MD, PhD, a specialist in aortic diseases and heart failure at Raboud University Medical Center, Nijmegan, the Netherlands.
Citing several studies, he suggested that the benefit of beta-blockers could also stem from their ability to reduce heart rate and aortic stiffness while ARBs are likely to inhibit the interaction between the renin-angiotensin system (RAS) and TGF-beta pathway. Each of these might participate in risk of aortic root growth, according to Dr. van Kimmenade, who was invited by ESC to discuss this study.
On the basis of these data as well as past studies, he agreed that the combination of beta-blockers and ARBs might not just be additive but “even a little bit synergistic.”
While Dr. Pitcher suggested that the evidence supports starting both beta-blockers and ARBs soon after the diagnosis, Dr. van Kimmenade said, “I don’t like using beta-blockers in young patients, but ARBs are now shown to be an excellent alternative.”
Ultimately, “the prescription pencil will not replace the surgical knife” in a disease that is likely to eventually require surgery to prevent life-threatening events, according to Dr. van Kimmenade, but he agreed that these data provide more certainty about the value of beta-blockers and ARBs for slowing progression.
Dr. Pitcher reports no potential conflicts of interest. Dr. van Kimmenade has financial relationships with Bayer and Novartis.
Beta-blockers have long been recommended to prevent aortic dissection associated with Marfan syndrome despite limited evidence, but a new analysis also supports a benefit from angiotensin receptors blockers (ARBs) and further suggests that beta-blockers and ARBs exert independent effects.
For the endpoint of inhibition of growth of the aortic root, “there is no evidence of any interaction between the effects of ARBs with beta-blockers, and so we think that the treatment effects are likely to be additive,” reported Alex Pitcher, BMBCh, DPhil, Oxford (England) University Hospitals, NHS Trust.
Based on these data, Dr. Pitcher recommended considering ARBs and beta-blockers together soon after the diagnosis of Marfan syndrome. This includes young children.
“We think that medical treatments can delay surgery and dissection substantially if given for a number of years,” he added.
In this study, undertaken by the Marfan Treatment Trialists (MTT) collaboration, data were available from 1,442 Marfan syndrome patients participating in seven treatment trials. The primary outcome was aortic root enlargement, a predictor of life-threatening aortic dissection and rupture. Rather than a meta-analysis of the pooled data, the meta-analysis was conducted with individual patient data that involved collaboration with the original trialists.
Four of the studies with 746 patients compared ARBs to placebo or a control medication. A second group of three trials with 766 patients compared ARBs to beta-blockers.
From the two sets of data, a calculation of the effect of beta-blockers was indirectly estimated.
ARBs slow annualized aortic growth rate significantly
In the first set of trials, the analysis showed a significantly slower annualized aortic root growth rate for those treated with ARBs relative to controls (0.07 vs. 0.13), producing a statistically significant absolute difference (0.7%; P = .01) in favor of the ARB.
“In other words, the rate of growth was nearly double in the control arm,” Dr. Pitcher said.
In the three trials comparing ARBs to beta-blockers, the annualized growth rate among those taking an ARB was similar (0.8%) to that seen in the previous set of controlled trials. This rate of annualized growth was not significantly different from the 0.11% annualized rate of growth in patients receiving beta-blockers. When an analysis of the impact of beta-blockers was conducted by indirectly evaluating the change in growth relative to controls, the estimated impact was an annualized growth rate of 0.9% (P = .042).
A second set of data provided the basis for suggesting that the effects of beta ARBs and beta-blockers are independent and potentially additive.
“We were able to look at subgroups of patients in the ARB trials that were broken down by whether they were or were not on beta-blockers at baseline, and so by doing able to estimate independent effects,” Dr. Pitcher said. The lack of any interactions led Dr. Pitcher to conclude that benefits are likely additive.
Of patients genotyped in the ARB studies, more than 80% had the FBN1 pathogenic variant of Marfan syndrome. When the data were analyzed by subgroups, including age or blood pressure, there were no differences in treatment effect except for those with the FBN1 mutation in whom the benefit of ARB therapy was greater relative to those without.
As FBN1 is one of the most common genetic signatures of Marfan syndrome, the “greater effect of ARBs in this group makes it more plausible that the effect is real,” Dr. Pitcher said.
Results could change treatment guidelines
Current guidelines recommend beta-blockers in Marfan syndrome prior to a dilatation size of 4.5 to 5 cm when surgery is indicated, according to Dr. Pitcher, but he said these data might change guidelines. While reinforcing the benefit of beta-blockers, this analysis suggests ARBs should also be considered, possibly in combination with beta-blockers.
“What I hope this meta-analysis does is add substantially to the certainty with which physicians can discuss treatments with patients.”
As for the mechanism, it is reasonable to speculate the antihypertensive effect of both medications is relevant, but each has plausible independent activities that might contribute to modifying aortic growth, according to Roland R.J. van Kimmenade, MD, PhD, a specialist in aortic diseases and heart failure at Raboud University Medical Center, Nijmegan, the Netherlands.
Citing several studies, he suggested that the benefit of beta-blockers could also stem from their ability to reduce heart rate and aortic stiffness while ARBs are likely to inhibit the interaction between the renin-angiotensin system (RAS) and TGF-beta pathway. Each of these might participate in risk of aortic root growth, according to Dr. van Kimmenade, who was invited by ESC to discuss this study.
On the basis of these data as well as past studies, he agreed that the combination of beta-blockers and ARBs might not just be additive but “even a little bit synergistic.”
While Dr. Pitcher suggested that the evidence supports starting both beta-blockers and ARBs soon after the diagnosis, Dr. van Kimmenade said, “I don’t like using beta-blockers in young patients, but ARBs are now shown to be an excellent alternative.”
Ultimately, “the prescription pencil will not replace the surgical knife” in a disease that is likely to eventually require surgery to prevent life-threatening events, according to Dr. van Kimmenade, but he agreed that these data provide more certainty about the value of beta-blockers and ARBs for slowing progression.
Dr. Pitcher reports no potential conflicts of interest. Dr. van Kimmenade has financial relationships with Bayer and Novartis.
FROM ESC CONGRESS 2022
AHA statement outlines symptoms of common heart diseases
Symptoms of six common cardiovascular diseases (CVD) – acute coronary syndromes, heart failure, valvular disorders, stroke, rhythm disorders, and peripheral vascular disease – often overlap and may vary over time and by sex, the American Heart Association noted in a new scientific statement.
“Symptoms of these cardiovascular diseases can profoundly affect quality of life, and a clear understanding of them is critical for effective diagnosis and treatment decisions,” Corrine Y. Jurgens, PhD, chair of the writing committee, said in a news release.
This scientific statement is a “compendium detailing the symptoms associated with CVD, similarities or differences in symptoms among the conditions, and sex differences in symptom presentation and reporting,” said Dr. Jurgens, associate professor at Connell School of Nursing, Boston College.
The new statement was published online in Circulation.
The writing group noted that measuring CVD symptoms can be challenging because of their subjective nature. Symptoms may go unrecognized or unreported if people don’t think they are important or are related to an existing health condition.
“Some people may not consider symptoms like fatigue, sleep disturbance, weight gain, and depression as important or related to cardiovascular disease. However, research indicates that subtle symptoms such as these may predict acute events and the need for hospitalization,” Dr. Jurgens said.
ACS – chest pain and associated symptoms
The writing group noted that chest pain is the most frequently reported symptom of ACS and has often been described as substernal pressure or discomfort and may radiate to the jaw, shoulder, arm, or upper back.
The most common co-occurring symptoms are dyspnea, diaphoresis, unusual fatigue, nausea, and lightheadedness. Women are more likely than men to report additional symptoms outside of chest pain.
As a result, they have often been labeled “atypical.” However, a recent AHA advisory notes that this label may have been caused by the lack of women included in the clinical trials from which the symptom lists were derived.
The writing group said there is a need to “harmonize” ACS symptom measurement in research. The current lack of harmonization of ACS symptom measurement in research hampers growth in cumulative evidence.
“Therefore, little can be done to synthesize salient findings about symptoms across ischemic heart disease/ACS studies and to incorporate evidence-based information about symptoms into treatment guidelines and patient education materials,” they cautioned.
Heart failure
Turning to heart failure (HF), the writing group noted that dyspnea is the classic symptom and a common reason adults seek medical care.
However, early, more subtle symptoms should be recognized. These include gastrointestinal symptoms such as upset stomach, nausea, vomiting, and loss of appetite; fatigue; exercise intolerance; insomnia; pain (chest and otherwise); mood disturbances (primarily depression and anxiety); and cognitive dysfunction (brain fog, memory problems).
Women with HF report a wider variety of symptoms, are more likely to have depression and anxiety, and report a lower quality of life, compared with men with HF.
“It is important to account for dyspnea heterogeneity in both clinical practice and research by using nuanced measures and probing questions to capture this common and multifaceted symptom,” the writing group said.
“Monitoring symptoms on a spectrum, versus present or not present, with reliable and valid measures may enhance clinical care by identifying more quickly those who may be at risk for poor outcomes, such as lower quality of life, hospitalization, or death,” Dr. Jurgens added.
“Ultimately, we have work to do in terms of determining who needs more frequent monitoring or intervention to avert poor HF outcomes,” she said.
Valvular heart disease
Valvular heart disease is a frequent cause of HF, with symptoms generally indistinguishable from other HF causes. Rheumatic heart disease is still prevalent in low- and middle-income countries but has largely disappeared in high-income countries, with population aging and cardiomyopathies now key drivers of valve disease.
In the absence of acute severe valve dysfunction, patients generally have a prolonged asymptomatic period, followed by a period of progressive symptoms, resulting from the valve lesion itself or secondary myocardial remodeling and dysfunction, the writing group said.
Symptoms of aortic valve disease often differ between men and women. Aortic stenosis is typically silent for years. As stenosis progresses, women report dyspnea and exercise intolerance more often than men. Women are also more likely to be physically frail and to have a higher New York Heart Association class (III/IV) than men. Men are more likely to have chest pain.
“Given the importance of symptom assessment, more work is needed to determine the incremental value of quantitative symptom measurement as an aid to clinical management,” the writing group said.
Stroke
For clinicians, classic stroke symptoms (face drooping, arm weakness, speech difficulty), in addition to nonclassic symptoms, such as partial sensory deficit, dysarthria, vertigo, and diplopia, should be considered for activating a stroke response team, the group says.
A systematic review and meta-analysis revealed that women with stroke were more likely to present with nonfocal symptoms (for example, headache, altered mentality, and coma/stupor) than men, they noted.
To enhance public education about stroke symptoms and to facilitate the diagnosis and treatment of stroke, they say research is needed to better understand the presentation of stroke symptoms by other select demographic characteristics including race and ethnicity, age, and stroke subtype.
Poststroke screening should include assessment for anxiety, depression, fatigue, and pain, the writing group said.
Rhythm disorders
Turning to rhythm disorders, the writing group wrote that cardiac arrhythmias, including atrial fibrillation (AFib), atrial flutter, supraventricular tachycardia, bradyarrhythmia, and ventricular tachycardia, present with common symptoms.
Palpitations are a characteristic symptom of many cardiac arrhythmias. The most common cardiac arrhythmia, AFib, may present with palpitations or less specific symptoms (fatigue, dyspnea, dizziness) that occur with a broad range of rhythm disorders. Chest pain, dizziness, presyncope/syncope, and anxiety occur less frequently in AFib, the group said.
Palpitations are considered the typical symptom presentation for AFib, yet patients with new-onset AFib often present with nonspecific symptoms or no symptoms, they pointed out.
Women and younger individuals with AFib typically present with palpitations, whereas men are more commonly asymptomatic. Older age also increases the likelihood of a nonclassic or asymptomatic presentation of AFib.
Despite non-Hispanic Black individuals being at lower risk for development of AFib, research suggests that Black patients are burdened more with palpitations, dyspnea on exertion, exercise intolerance, dizziness, dyspnea at rest, and chest discomfort, compared with White or Hispanic patients.
Peripheral vascular disease
Classic claudication occurs in roughly one-third of patients with peripheral arterial disease (PAD) and is defined as calf pain that occurs in one or both legs with exertion (walking), does not begin at rest, and resolves within 10 minutes of standing still or rest.
However, non–calf exercise pain is reported more frequently than classic claudication symptoms. Women with PAD are more likely to have nonclassic symptoms or an absence of symptoms.
Assessing symptoms at rest, during exercise, and during recovery can assist with classifying symptoms as ischemic or not, the writing group said.
PAD with symptoms is associated with an increased risk for myocardial infarction and stroke, with men at higher risk than women.
Similar to PAD, peripheral venous disease (PVD) can be symptomatic or asymptomatic. Clinical classification of PVD includes symptoms such as leg pain, aching, fatigue, heaviness, cramping, tightness, restless legs syndrome, and skin irritation.
“Measuring vascular symptoms includes assessing quality of life and activity limitations, as well as the psychological impact of the disease. However, existing measures are often based on the clinician’s appraisal rather than the individual’s self-reported symptoms and severity of symptoms,” Dr. Jurgens commented.
Watch for depression
Finally, the writing group highlighted the importance of depression in cardiac patients, which occurs at about twice the rate, compared with people without any medical condition (10% vs. 5%).
In a prior statement, the AHA said depression should be considered a risk factor for worse outcomes in patients with ACS or CVD diagnosis.
The new statement highlights that people with persistent chest pain, people with HF, as well as stroke survivors and people with PAD commonly have depression and/or anxiety. In addition, cognitive changes after a stroke may affect how and whether symptoms are experienced or noticed.
While symptom relief is an important part of managing CVD, it’s also important to recognize that “factors such as depression and cognitive function may affect symptom detection and reporting,” Dr. Jurgens said.
“Monitoring and measuring symptoms with tools that appropriately account for depression and cognitive function may help to improve patient care by identifying more quickly people who may be at higher risk,” she added.
The scientific statement was prepared by the volunteer writing group on behalf of the AHA Council on Cardiovascular and Stroke Nursing; the Council on Hypertension; and the Stroke Council. The research had no commercial funding. The authors reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Symptoms of six common cardiovascular diseases (CVD) – acute coronary syndromes, heart failure, valvular disorders, stroke, rhythm disorders, and peripheral vascular disease – often overlap and may vary over time and by sex, the American Heart Association noted in a new scientific statement.
“Symptoms of these cardiovascular diseases can profoundly affect quality of life, and a clear understanding of them is critical for effective diagnosis and treatment decisions,” Corrine Y. Jurgens, PhD, chair of the writing committee, said in a news release.
This scientific statement is a “compendium detailing the symptoms associated with CVD, similarities or differences in symptoms among the conditions, and sex differences in symptom presentation and reporting,” said Dr. Jurgens, associate professor at Connell School of Nursing, Boston College.
The new statement was published online in Circulation.
The writing group noted that measuring CVD symptoms can be challenging because of their subjective nature. Symptoms may go unrecognized or unreported if people don’t think they are important or are related to an existing health condition.
“Some people may not consider symptoms like fatigue, sleep disturbance, weight gain, and depression as important or related to cardiovascular disease. However, research indicates that subtle symptoms such as these may predict acute events and the need for hospitalization,” Dr. Jurgens said.
ACS – chest pain and associated symptoms
The writing group noted that chest pain is the most frequently reported symptom of ACS and has often been described as substernal pressure or discomfort and may radiate to the jaw, shoulder, arm, or upper back.
The most common co-occurring symptoms are dyspnea, diaphoresis, unusual fatigue, nausea, and lightheadedness. Women are more likely than men to report additional symptoms outside of chest pain.
As a result, they have often been labeled “atypical.” However, a recent AHA advisory notes that this label may have been caused by the lack of women included in the clinical trials from which the symptom lists were derived.
The writing group said there is a need to “harmonize” ACS symptom measurement in research. The current lack of harmonization of ACS symptom measurement in research hampers growth in cumulative evidence.
“Therefore, little can be done to synthesize salient findings about symptoms across ischemic heart disease/ACS studies and to incorporate evidence-based information about symptoms into treatment guidelines and patient education materials,” they cautioned.
Heart failure
Turning to heart failure (HF), the writing group noted that dyspnea is the classic symptom and a common reason adults seek medical care.
However, early, more subtle symptoms should be recognized. These include gastrointestinal symptoms such as upset stomach, nausea, vomiting, and loss of appetite; fatigue; exercise intolerance; insomnia; pain (chest and otherwise); mood disturbances (primarily depression and anxiety); and cognitive dysfunction (brain fog, memory problems).
Women with HF report a wider variety of symptoms, are more likely to have depression and anxiety, and report a lower quality of life, compared with men with HF.
“It is important to account for dyspnea heterogeneity in both clinical practice and research by using nuanced measures and probing questions to capture this common and multifaceted symptom,” the writing group said.
“Monitoring symptoms on a spectrum, versus present or not present, with reliable and valid measures may enhance clinical care by identifying more quickly those who may be at risk for poor outcomes, such as lower quality of life, hospitalization, or death,” Dr. Jurgens added.
“Ultimately, we have work to do in terms of determining who needs more frequent monitoring or intervention to avert poor HF outcomes,” she said.
Valvular heart disease
Valvular heart disease is a frequent cause of HF, with symptoms generally indistinguishable from other HF causes. Rheumatic heart disease is still prevalent in low- and middle-income countries but has largely disappeared in high-income countries, with population aging and cardiomyopathies now key drivers of valve disease.
In the absence of acute severe valve dysfunction, patients generally have a prolonged asymptomatic period, followed by a period of progressive symptoms, resulting from the valve lesion itself or secondary myocardial remodeling and dysfunction, the writing group said.
Symptoms of aortic valve disease often differ between men and women. Aortic stenosis is typically silent for years. As stenosis progresses, women report dyspnea and exercise intolerance more often than men. Women are also more likely to be physically frail and to have a higher New York Heart Association class (III/IV) than men. Men are more likely to have chest pain.
“Given the importance of symptom assessment, more work is needed to determine the incremental value of quantitative symptom measurement as an aid to clinical management,” the writing group said.
Stroke
For clinicians, classic stroke symptoms (face drooping, arm weakness, speech difficulty), in addition to nonclassic symptoms, such as partial sensory deficit, dysarthria, vertigo, and diplopia, should be considered for activating a stroke response team, the group says.
A systematic review and meta-analysis revealed that women with stroke were more likely to present with nonfocal symptoms (for example, headache, altered mentality, and coma/stupor) than men, they noted.
To enhance public education about stroke symptoms and to facilitate the diagnosis and treatment of stroke, they say research is needed to better understand the presentation of stroke symptoms by other select demographic characteristics including race and ethnicity, age, and stroke subtype.
Poststroke screening should include assessment for anxiety, depression, fatigue, and pain, the writing group said.
Rhythm disorders
Turning to rhythm disorders, the writing group wrote that cardiac arrhythmias, including atrial fibrillation (AFib), atrial flutter, supraventricular tachycardia, bradyarrhythmia, and ventricular tachycardia, present with common symptoms.
Palpitations are a characteristic symptom of many cardiac arrhythmias. The most common cardiac arrhythmia, AFib, may present with palpitations or less specific symptoms (fatigue, dyspnea, dizziness) that occur with a broad range of rhythm disorders. Chest pain, dizziness, presyncope/syncope, and anxiety occur less frequently in AFib, the group said.
Palpitations are considered the typical symptom presentation for AFib, yet patients with new-onset AFib often present with nonspecific symptoms or no symptoms, they pointed out.
Women and younger individuals with AFib typically present with palpitations, whereas men are more commonly asymptomatic. Older age also increases the likelihood of a nonclassic or asymptomatic presentation of AFib.
Despite non-Hispanic Black individuals being at lower risk for development of AFib, research suggests that Black patients are burdened more with palpitations, dyspnea on exertion, exercise intolerance, dizziness, dyspnea at rest, and chest discomfort, compared with White or Hispanic patients.
Peripheral vascular disease
Classic claudication occurs in roughly one-third of patients with peripheral arterial disease (PAD) and is defined as calf pain that occurs in one or both legs with exertion (walking), does not begin at rest, and resolves within 10 minutes of standing still or rest.
However, non–calf exercise pain is reported more frequently than classic claudication symptoms. Women with PAD are more likely to have nonclassic symptoms or an absence of symptoms.
Assessing symptoms at rest, during exercise, and during recovery can assist with classifying symptoms as ischemic or not, the writing group said.
PAD with symptoms is associated with an increased risk for myocardial infarction and stroke, with men at higher risk than women.
Similar to PAD, peripheral venous disease (PVD) can be symptomatic or asymptomatic. Clinical classification of PVD includes symptoms such as leg pain, aching, fatigue, heaviness, cramping, tightness, restless legs syndrome, and skin irritation.
“Measuring vascular symptoms includes assessing quality of life and activity limitations, as well as the psychological impact of the disease. However, existing measures are often based on the clinician’s appraisal rather than the individual’s self-reported symptoms and severity of symptoms,” Dr. Jurgens commented.
Watch for depression
Finally, the writing group highlighted the importance of depression in cardiac patients, which occurs at about twice the rate, compared with people without any medical condition (10% vs. 5%).
In a prior statement, the AHA said depression should be considered a risk factor for worse outcomes in patients with ACS or CVD diagnosis.
The new statement highlights that people with persistent chest pain, people with HF, as well as stroke survivors and people with PAD commonly have depression and/or anxiety. In addition, cognitive changes after a stroke may affect how and whether symptoms are experienced or noticed.
While symptom relief is an important part of managing CVD, it’s also important to recognize that “factors such as depression and cognitive function may affect symptom detection and reporting,” Dr. Jurgens said.
“Monitoring and measuring symptoms with tools that appropriately account for depression and cognitive function may help to improve patient care by identifying more quickly people who may be at higher risk,” she added.
The scientific statement was prepared by the volunteer writing group on behalf of the AHA Council on Cardiovascular and Stroke Nursing; the Council on Hypertension; and the Stroke Council. The research had no commercial funding. The authors reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Symptoms of six common cardiovascular diseases (CVD) – acute coronary syndromes, heart failure, valvular disorders, stroke, rhythm disorders, and peripheral vascular disease – often overlap and may vary over time and by sex, the American Heart Association noted in a new scientific statement.
“Symptoms of these cardiovascular diseases can profoundly affect quality of life, and a clear understanding of them is critical for effective diagnosis and treatment decisions,” Corrine Y. Jurgens, PhD, chair of the writing committee, said in a news release.
This scientific statement is a “compendium detailing the symptoms associated with CVD, similarities or differences in symptoms among the conditions, and sex differences in symptom presentation and reporting,” said Dr. Jurgens, associate professor at Connell School of Nursing, Boston College.
The new statement was published online in Circulation.
The writing group noted that measuring CVD symptoms can be challenging because of their subjective nature. Symptoms may go unrecognized or unreported if people don’t think they are important or are related to an existing health condition.
“Some people may not consider symptoms like fatigue, sleep disturbance, weight gain, and depression as important or related to cardiovascular disease. However, research indicates that subtle symptoms such as these may predict acute events and the need for hospitalization,” Dr. Jurgens said.
ACS – chest pain and associated symptoms
The writing group noted that chest pain is the most frequently reported symptom of ACS and has often been described as substernal pressure or discomfort and may radiate to the jaw, shoulder, arm, or upper back.
The most common co-occurring symptoms are dyspnea, diaphoresis, unusual fatigue, nausea, and lightheadedness. Women are more likely than men to report additional symptoms outside of chest pain.
As a result, they have often been labeled “atypical.” However, a recent AHA advisory notes that this label may have been caused by the lack of women included in the clinical trials from which the symptom lists were derived.
The writing group said there is a need to “harmonize” ACS symptom measurement in research. The current lack of harmonization of ACS symptom measurement in research hampers growth in cumulative evidence.
“Therefore, little can be done to synthesize salient findings about symptoms across ischemic heart disease/ACS studies and to incorporate evidence-based information about symptoms into treatment guidelines and patient education materials,” they cautioned.
Heart failure
Turning to heart failure (HF), the writing group noted that dyspnea is the classic symptom and a common reason adults seek medical care.
However, early, more subtle symptoms should be recognized. These include gastrointestinal symptoms such as upset stomach, nausea, vomiting, and loss of appetite; fatigue; exercise intolerance; insomnia; pain (chest and otherwise); mood disturbances (primarily depression and anxiety); and cognitive dysfunction (brain fog, memory problems).
Women with HF report a wider variety of symptoms, are more likely to have depression and anxiety, and report a lower quality of life, compared with men with HF.
“It is important to account for dyspnea heterogeneity in both clinical practice and research by using nuanced measures and probing questions to capture this common and multifaceted symptom,” the writing group said.
“Monitoring symptoms on a spectrum, versus present or not present, with reliable and valid measures may enhance clinical care by identifying more quickly those who may be at risk for poor outcomes, such as lower quality of life, hospitalization, or death,” Dr. Jurgens added.
“Ultimately, we have work to do in terms of determining who needs more frequent monitoring or intervention to avert poor HF outcomes,” she said.
Valvular heart disease
Valvular heart disease is a frequent cause of HF, with symptoms generally indistinguishable from other HF causes. Rheumatic heart disease is still prevalent in low- and middle-income countries but has largely disappeared in high-income countries, with population aging and cardiomyopathies now key drivers of valve disease.
In the absence of acute severe valve dysfunction, patients generally have a prolonged asymptomatic period, followed by a period of progressive symptoms, resulting from the valve lesion itself or secondary myocardial remodeling and dysfunction, the writing group said.
Symptoms of aortic valve disease often differ between men and women. Aortic stenosis is typically silent for years. As stenosis progresses, women report dyspnea and exercise intolerance more often than men. Women are also more likely to be physically frail and to have a higher New York Heart Association class (III/IV) than men. Men are more likely to have chest pain.
“Given the importance of symptom assessment, more work is needed to determine the incremental value of quantitative symptom measurement as an aid to clinical management,” the writing group said.
Stroke
For clinicians, classic stroke symptoms (face drooping, arm weakness, speech difficulty), in addition to nonclassic symptoms, such as partial sensory deficit, dysarthria, vertigo, and diplopia, should be considered for activating a stroke response team, the group says.
A systematic review and meta-analysis revealed that women with stroke were more likely to present with nonfocal symptoms (for example, headache, altered mentality, and coma/stupor) than men, they noted.
To enhance public education about stroke symptoms and to facilitate the diagnosis and treatment of stroke, they say research is needed to better understand the presentation of stroke symptoms by other select demographic characteristics including race and ethnicity, age, and stroke subtype.
Poststroke screening should include assessment for anxiety, depression, fatigue, and pain, the writing group said.
Rhythm disorders
Turning to rhythm disorders, the writing group wrote that cardiac arrhythmias, including atrial fibrillation (AFib), atrial flutter, supraventricular tachycardia, bradyarrhythmia, and ventricular tachycardia, present with common symptoms.
Palpitations are a characteristic symptom of many cardiac arrhythmias. The most common cardiac arrhythmia, AFib, may present with palpitations or less specific symptoms (fatigue, dyspnea, dizziness) that occur with a broad range of rhythm disorders. Chest pain, dizziness, presyncope/syncope, and anxiety occur less frequently in AFib, the group said.
Palpitations are considered the typical symptom presentation for AFib, yet patients with new-onset AFib often present with nonspecific symptoms or no symptoms, they pointed out.
Women and younger individuals with AFib typically present with palpitations, whereas men are more commonly asymptomatic. Older age also increases the likelihood of a nonclassic or asymptomatic presentation of AFib.
Despite non-Hispanic Black individuals being at lower risk for development of AFib, research suggests that Black patients are burdened more with palpitations, dyspnea on exertion, exercise intolerance, dizziness, dyspnea at rest, and chest discomfort, compared with White or Hispanic patients.
Peripheral vascular disease
Classic claudication occurs in roughly one-third of patients with peripheral arterial disease (PAD) and is defined as calf pain that occurs in one or both legs with exertion (walking), does not begin at rest, and resolves within 10 minutes of standing still or rest.
However, non–calf exercise pain is reported more frequently than classic claudication symptoms. Women with PAD are more likely to have nonclassic symptoms or an absence of symptoms.
Assessing symptoms at rest, during exercise, and during recovery can assist with classifying symptoms as ischemic or not, the writing group said.
PAD with symptoms is associated with an increased risk for myocardial infarction and stroke, with men at higher risk than women.
Similar to PAD, peripheral venous disease (PVD) can be symptomatic or asymptomatic. Clinical classification of PVD includes symptoms such as leg pain, aching, fatigue, heaviness, cramping, tightness, restless legs syndrome, and skin irritation.
“Measuring vascular symptoms includes assessing quality of life and activity limitations, as well as the psychological impact of the disease. However, existing measures are often based on the clinician’s appraisal rather than the individual’s self-reported symptoms and severity of symptoms,” Dr. Jurgens commented.
Watch for depression
Finally, the writing group highlighted the importance of depression in cardiac patients, which occurs at about twice the rate, compared with people without any medical condition (10% vs. 5%).
In a prior statement, the AHA said depression should be considered a risk factor for worse outcomes in patients with ACS or CVD diagnosis.
The new statement highlights that people with persistent chest pain, people with HF, as well as stroke survivors and people with PAD commonly have depression and/or anxiety. In addition, cognitive changes after a stroke may affect how and whether symptoms are experienced or noticed.
While symptom relief is an important part of managing CVD, it’s also important to recognize that “factors such as depression and cognitive function may affect symptom detection and reporting,” Dr. Jurgens said.
“Monitoring and measuring symptoms with tools that appropriately account for depression and cognitive function may help to improve patient care by identifying more quickly people who may be at higher risk,” she added.
The scientific statement was prepared by the volunteer writing group on behalf of the AHA Council on Cardiovascular and Stroke Nursing; the Council on Hypertension; and the Stroke Council. The research had no commercial funding. The authors reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM CIRCULATION
For patients with peripheral artery disease, pain can be gain
For people with peripheral artery disease (PAD), even short walks can be exercises in excruciation.
But a new study published in the Journal of the American Heart Association has found that patients who can push through the pain appear to reap significant benefits in ambulation, balance, and leg strength, which have been linked to increased longevity.
“You have to push yourself and get those uncomfortable symptoms, or else you probably won’t get gains,” said Mary McDermott, MD, professor of medicine at Northwestern University, Chicago, and the senior author of the study.
Walking for exercise is critical for people with lower-extremity PAD, Dr. McDermott said, but leg pain dissuades many people with the condition from doing so. She said her group hopes that showing the payoff of the “no pain, no gain” approach gives people with PAD the resolve to walk regularly, even when it’s hard.
The new study, a post hoc analysis of the LITE (Low-Intensity Exercise Intervention in PAD) trial, found that low-intensity exercise did not improve the symptoms of PAD but high-intensity exercise did.
Dr. McDermott and her colleagues compared 109 people with PAD who walked fast enough to cause discomfort versus 101 people who walked at a comfortable pace and 54 people who did not exercise at all. The average age was 69 years, 48% of participants were women, and 61% were Black.
Everyone in the exercise groups walked at home, with visits to a medical center early in the study to get exercise tips and then phone support from exercise coaches throughout the remainder of the study. Researchers encouraged those in the discomfort group to walk fast enough to cause significant pain in their legs, for up to 10 minutes or as long as they could. They then rested before walking again, ideally up to five times per day for 5 days per week.
At 6 months, people in the discomfort group were walking 0.056 m/sec faster than those in the comfort group during a 4-meter walking test (95% confidence interval [CI], 0.19-0.094 m/sec; P < .01), a gap that had grown by 12 months to 0.084 m/sec (95% CI, 0.049-0.120 m/sec; P <.01), according to the researchers. A statistically significant gap also emerged between the discomfort and nonexercising group at 6 months, but it eventually closed.
“It’s a question that people have asked for some time: Is it necessary to get that ischemic pain when you walk?” Dr. McDermott said. “This is the first well-powered clinical trial to provide a definitive answer on that, and the answer is that you do need that discomfort. It wasn’t even close.” Indeed, Dr. McDermott said, it’s possible that walking merely to the point of comfort and never pushing beyond it may harm people with PAD.
At the 6-month mark, the researchers found no statistical difference between the discomfort and comfort groups on a cumulative scale of usual walking speed, ability to rise from a chair, and ability to maintain balance in several positions. By 12 months, the two groups had diverged, with the discomfort group improving by almost 1 point on the scale, whereas the performance of the comfort group declined. No significant differences emerged between the discomfort and nonexercising groups, the researchers reported.
The investigators found, counterintuitively, that some people in the study who did not record exercising did as well as those in the discomfort group,
Dr. McDermott noted that the nonexercise group was smaller than the discomfort group, making firm comparisons between the two challenging to draw. In addition, people whose exercise was not recorded were not asked to take it easy whenever they walked, unlike those in the comfort group. As a result, she said, some people in this group may have walked vigorously.
Dr. McDermott emphasized that these benefits occurred at home rather than at medical centers that can be difficult for some people to visit regularly.
“It’s always good to have this kind of information for patients, to show them that it’s possible for them to continue to improve,” said Jonathan Ehrman, PhD, associate director of preventive cardiology at Henry Ford Medical Center, Detroit. Dr. Ehrman was not involved in this study but said that he is contemplating running a similar home-based study that would use video rather than telephone support for patients.
“There’s emerging data about walking speed being related to longevity and predicting better outcomes in cardiac surgeries,” Dr. Ehrman said. “It seems to be, if you can get people walking faster or they have a better walking pace, related to better health outcomes.”
Dr. McDermott reported relationships with Regeneron, Helixmith, Mars, ArtAssist, ReserveAge, and Hershey. Dr. Ehrman reported no relevant financial conflicts of interest.
A version of this article first appeared on Medscape.com.
For people with peripheral artery disease (PAD), even short walks can be exercises in excruciation.
But a new study published in the Journal of the American Heart Association has found that patients who can push through the pain appear to reap significant benefits in ambulation, balance, and leg strength, which have been linked to increased longevity.
“You have to push yourself and get those uncomfortable symptoms, or else you probably won’t get gains,” said Mary McDermott, MD, professor of medicine at Northwestern University, Chicago, and the senior author of the study.
Walking for exercise is critical for people with lower-extremity PAD, Dr. McDermott said, but leg pain dissuades many people with the condition from doing so. She said her group hopes that showing the payoff of the “no pain, no gain” approach gives people with PAD the resolve to walk regularly, even when it’s hard.
The new study, a post hoc analysis of the LITE (Low-Intensity Exercise Intervention in PAD) trial, found that low-intensity exercise did not improve the symptoms of PAD but high-intensity exercise did.
Dr. McDermott and her colleagues compared 109 people with PAD who walked fast enough to cause discomfort versus 101 people who walked at a comfortable pace and 54 people who did not exercise at all. The average age was 69 years, 48% of participants were women, and 61% were Black.
Everyone in the exercise groups walked at home, with visits to a medical center early in the study to get exercise tips and then phone support from exercise coaches throughout the remainder of the study. Researchers encouraged those in the discomfort group to walk fast enough to cause significant pain in their legs, for up to 10 minutes or as long as they could. They then rested before walking again, ideally up to five times per day for 5 days per week.
At 6 months, people in the discomfort group were walking 0.056 m/sec faster than those in the comfort group during a 4-meter walking test (95% confidence interval [CI], 0.19-0.094 m/sec; P < .01), a gap that had grown by 12 months to 0.084 m/sec (95% CI, 0.049-0.120 m/sec; P <.01), according to the researchers. A statistically significant gap also emerged between the discomfort and nonexercising group at 6 months, but it eventually closed.
“It’s a question that people have asked for some time: Is it necessary to get that ischemic pain when you walk?” Dr. McDermott said. “This is the first well-powered clinical trial to provide a definitive answer on that, and the answer is that you do need that discomfort. It wasn’t even close.” Indeed, Dr. McDermott said, it’s possible that walking merely to the point of comfort and never pushing beyond it may harm people with PAD.
At the 6-month mark, the researchers found no statistical difference between the discomfort and comfort groups on a cumulative scale of usual walking speed, ability to rise from a chair, and ability to maintain balance in several positions. By 12 months, the two groups had diverged, with the discomfort group improving by almost 1 point on the scale, whereas the performance of the comfort group declined. No significant differences emerged between the discomfort and nonexercising groups, the researchers reported.
The investigators found, counterintuitively, that some people in the study who did not record exercising did as well as those in the discomfort group,
Dr. McDermott noted that the nonexercise group was smaller than the discomfort group, making firm comparisons between the two challenging to draw. In addition, people whose exercise was not recorded were not asked to take it easy whenever they walked, unlike those in the comfort group. As a result, she said, some people in this group may have walked vigorously.
Dr. McDermott emphasized that these benefits occurred at home rather than at medical centers that can be difficult for some people to visit regularly.
“It’s always good to have this kind of information for patients, to show them that it’s possible for them to continue to improve,” said Jonathan Ehrman, PhD, associate director of preventive cardiology at Henry Ford Medical Center, Detroit. Dr. Ehrman was not involved in this study but said that he is contemplating running a similar home-based study that would use video rather than telephone support for patients.
“There’s emerging data about walking speed being related to longevity and predicting better outcomes in cardiac surgeries,” Dr. Ehrman said. “It seems to be, if you can get people walking faster or they have a better walking pace, related to better health outcomes.”
Dr. McDermott reported relationships with Regeneron, Helixmith, Mars, ArtAssist, ReserveAge, and Hershey. Dr. Ehrman reported no relevant financial conflicts of interest.
A version of this article first appeared on Medscape.com.
For people with peripheral artery disease (PAD), even short walks can be exercises in excruciation.
But a new study published in the Journal of the American Heart Association has found that patients who can push through the pain appear to reap significant benefits in ambulation, balance, and leg strength, which have been linked to increased longevity.
“You have to push yourself and get those uncomfortable symptoms, or else you probably won’t get gains,” said Mary McDermott, MD, professor of medicine at Northwestern University, Chicago, and the senior author of the study.
Walking for exercise is critical for people with lower-extremity PAD, Dr. McDermott said, but leg pain dissuades many people with the condition from doing so. She said her group hopes that showing the payoff of the “no pain, no gain” approach gives people with PAD the resolve to walk regularly, even when it’s hard.
The new study, a post hoc analysis of the LITE (Low-Intensity Exercise Intervention in PAD) trial, found that low-intensity exercise did not improve the symptoms of PAD but high-intensity exercise did.
Dr. McDermott and her colleagues compared 109 people with PAD who walked fast enough to cause discomfort versus 101 people who walked at a comfortable pace and 54 people who did not exercise at all. The average age was 69 years, 48% of participants were women, and 61% were Black.
Everyone in the exercise groups walked at home, with visits to a medical center early in the study to get exercise tips and then phone support from exercise coaches throughout the remainder of the study. Researchers encouraged those in the discomfort group to walk fast enough to cause significant pain in their legs, for up to 10 minutes or as long as they could. They then rested before walking again, ideally up to five times per day for 5 days per week.
At 6 months, people in the discomfort group were walking 0.056 m/sec faster than those in the comfort group during a 4-meter walking test (95% confidence interval [CI], 0.19-0.094 m/sec; P < .01), a gap that had grown by 12 months to 0.084 m/sec (95% CI, 0.049-0.120 m/sec; P <.01), according to the researchers. A statistically significant gap also emerged between the discomfort and nonexercising group at 6 months, but it eventually closed.
“It’s a question that people have asked for some time: Is it necessary to get that ischemic pain when you walk?” Dr. McDermott said. “This is the first well-powered clinical trial to provide a definitive answer on that, and the answer is that you do need that discomfort. It wasn’t even close.” Indeed, Dr. McDermott said, it’s possible that walking merely to the point of comfort and never pushing beyond it may harm people with PAD.
At the 6-month mark, the researchers found no statistical difference between the discomfort and comfort groups on a cumulative scale of usual walking speed, ability to rise from a chair, and ability to maintain balance in several positions. By 12 months, the two groups had diverged, with the discomfort group improving by almost 1 point on the scale, whereas the performance of the comfort group declined. No significant differences emerged between the discomfort and nonexercising groups, the researchers reported.
The investigators found, counterintuitively, that some people in the study who did not record exercising did as well as those in the discomfort group,
Dr. McDermott noted that the nonexercise group was smaller than the discomfort group, making firm comparisons between the two challenging to draw. In addition, people whose exercise was not recorded were not asked to take it easy whenever they walked, unlike those in the comfort group. As a result, she said, some people in this group may have walked vigorously.
Dr. McDermott emphasized that these benefits occurred at home rather than at medical centers that can be difficult for some people to visit regularly.
“It’s always good to have this kind of information for patients, to show them that it’s possible for them to continue to improve,” said Jonathan Ehrman, PhD, associate director of preventive cardiology at Henry Ford Medical Center, Detroit. Dr. Ehrman was not involved in this study but said that he is contemplating running a similar home-based study that would use video rather than telephone support for patients.
“There’s emerging data about walking speed being related to longevity and predicting better outcomes in cardiac surgeries,” Dr. Ehrman said. “It seems to be, if you can get people walking faster or they have a better walking pace, related to better health outcomes.”
Dr. McDermott reported relationships with Regeneron, Helixmith, Mars, ArtAssist, ReserveAge, and Hershey. Dr. Ehrman reported no relevant financial conflicts of interest.
A version of this article first appeared on Medscape.com.