Stroke

PHOENIX — Thrombectomy is generally beneficial for patients from a low-income population who have a large vessel occlusion stroke presenting in the later time window and who can be identified as suitable for treatment without the need for advanced and costly imaging, a new Brazilian trial has shown.

“The RESILIENT-Extend trial is the first major study of thrombectomy in the late time window (8-24 h) conducted outside first-world countries and shows the procedure also has benefit in a lower socioeconomic status population without the need for costly imaging equipment,” said lead investigator Raul G. Nogueira, MD. 

“The trial expands the treatment window for thrombectomy globally with simplified selection criteria based on non-contrast CT, potentially altering current guidelines,” Dr. Nogueira said.

However, there were some caveats that need to be considered; in particular, a lack of benefit with thrombectomy in older patients (over 68 years of age), which Dr. Nogueira believes is a reflection of the particular population enrolled in this study. Specifically, he suggested that older age in this low socioeconomic status population is a surrogate for frailty, and the study may have identified frailty as a factor that correlates with reduced or lack of benefit of thrombectomy.

Dr. Nogueira, who is a professor of neurology and neurosurgery at the University of Pittsburgh, and Sheila Martins, MD, a professor of neurology at Hospital de Clinicas Porto Alegre in Brazil, presented the RESILIENT-Extend results at the International Stroke Conference presented by the American Stroke Association, a division of the American Heart Association.

Dr. Nogueira explained that the lack of available advanced imaging techniques is a major challenge for implementing endovascular therapy in an extended time window, especially in lower-income countries.

“Our main objective was to see if we could remove the need for advanced imaging to select patients with large vessel occlusion stroke in the late time window (8-24 h) for thrombectomy,” he said. “In this way, our trial overlaps somewhat with the MR CLEAN-LATE Trial conducted in the Netherlands, although the two trials were conducted in very different socioeconomic populations.”

The RESILIENT-Extend trial was conducted in the public health service of Brazil and involved a different population of people than have been included in other thrombectomy trials, which have mostly been conducted in first-world countries.

“The public health system in Brazil is not well-resourced and tends to care for patients at lower socioeconomic levels. These patients are fundamentally different from the average patients in the first-world recruited into most other thrombectomy trials,” Dr. Nogueira noted.

The trial enrolled 245 patients with a large vessel occlusion stroke within 8-24 hours of last known well. Patients were included who had a mismatch between the clinical severity as shown by the National Institutes of Health Stroke Scale (NIHSS) score and the stroke burden on imaging as measured by ASPECTS scores.

They had to have relatively high NIHSS scores (8 or more) showing more severe strokes but also a high ASPECTS score (5-10) excluding patients with large areas of ischemic brain. There was also a sliding scale that adjusted for age to avoid enrolling elderly patients with large strokes.

These patients were identified exclusively using non-contrast CT and CT angiography imaging.

The median age of patients included was 62-63 years. Dr. Nogueira pointed out that patients were slightly younger than seen in other thrombectomy trials, perhaps because in lower-middle-income countries strokes occur at a younger age. They also have a higher case fatality rate.

The median baseline NIHSS score was 16, and the median ASPECTS score was 7-8.

The median time to treatment was 12.5 hours, which is similar to other late window thrombectomy trials.
 

Conflicting Results on Shift Analysis

The primary outcome was a shift analysis of the modified Rankin Scale (mRS) disability score at 90 days.

This showed a bidirectional result, with thrombectomy increasing the chances of a good or excellent outcome (mRS, 0-3), but there was also a nonsignificant increased risk for a bad outcome (mRS, 5-6).

“This bidirectional result prevents a common odds ratio from being calculated, so the primary endpoint is not applicable,” Dr. Nogueira reported.

The researchers therefore used the secondary outcomes as the main results of the study.

These showed that the number of patients achieving a good outcome (mRS, 0-2) was significantly increased with thrombectomy (25% vs. 14%, adjusted odds ratio, 2.56; P = .012).

The number of patients achieving an excellent outcome (mRS, 0-1) was also significantly increased.

But these increases in good outcomes came at the cost of some patients having an increased risk for severe disability or death (mRS, 5-6).

The odds ratio for an mRS of 0-4 versus 5-6 was 0.71, and for an mRS of 0-5 versus 6, the odds ratio was 0.58. Both these results were nonsignificant.

Another anomaly in the RESILIENT-Extend trial was the observation of no benefit of thrombectomy seen in older patients.

“In general, trials of thrombectomy in the first world have shown a greater treatment effect in older patients, but this was not seen in our trial, where older patients (over 68 years) did not derive any benefit from the procedure,” Dr. Nogueira noted.

A similar observation was also seen in the first RESILIENT trial in patients treated within 8 hours of stroke onset, which was also conducted in Brazil, leading to the suggestion that it is related to the patient population included.

“In the Brazilian public health service, older patients are very vulnerable and frail. They are different to older patients in first world countries. It appears they may be too fragile to withstand the thrombectomy process,” Dr. Nogueira said.
 

Frailty: A Ceiling Effect?

Results from the two RESILIENT trials give a word of caution to the thrombectomy field, Dr. Nogueira said.

“This procedure was initially thought suitable only for patients with small core strokes, but we now have a series of trials showing benefit of thrombectomy in large core strokes as well,” Dr. Nogueira said. “We have started to believe that this intervention will benefit almost all patients with large vessel occlusion stroke everywhere around the world, but our data suggest that we have to consider the specific populations that we are serving and that factors such as socioeconomic status and frailty have to be taken into account.

“Both the RESILIENT trials have shown that thrombectomy does not appear to be suitable for older patients, over 68-70 years of age, in the public health service in Brazil,” he noted. “In this population, a patient aged 70 can be quite different to a patient of the same age in a first-world country. I think in our population, an age of over 68-70 is a surrogate for frailty, which will not be the case in first-world countries. In this regard, I think we have found a ceiling effect for benefit of thrombectomy, which is frailty.”

Dr. Nogueira speculated that the bidirectional effect on the mRS shift analysis may also have been caused by the frailty of some of the patients.

“What the results may be showing is that for most of the population, there is a benefit of thrombectomy, but for some patients, possibly the most frail, then the procedure can be too overwhelming for them. But the suggestion of harm was not significant, so this observation could have also just been the play of chance,” he added.
 

Interpreting the Findings

Commenting on the RESILIENT-Extend study results, Michael Hill, MD, professor of neurology at the University of Calgary, Canada, pointed out that there was an absolute benefit of 11.1% on the mRS of 0-2 outcome but a similar signal of harm, with a 10.2% increase in mortality in the thrombectomy group, although that was not statistically significant.

“This signal of harm appears not to be due to an increase in intracranial hemorrhage or procedural mishap,” he said. “It is unclear why there were more deaths; the overall trial numbers are small enough that this could be a chance finding.”

Dr. Hill also noted that the absolute proportion of patients achieving an independent functional outcome was 50% less than in the DAWN trial of thrombectomy in the extended window. “This tells us that the patients selected for inclusion into RESILIENT-Extend were physiologically different from those in DAWN,” he said.

Also commenting on the study, Amrou Sarraj, MD, professor of neurology at University Hospitals Cleveland Medical Center–Case Western Reserve University in Cleveland, said: “The RESILIENT-Extend investigators should be congratulated for the successful conduct of the trial and providing evidence of benefit of thrombectomy procedure with simplified neuroimaging protocol using CT and CTA in resource-limited settings. These findings will help support extending the access to thrombectomy in areas without availability of advanced imaging.”

He said the bidirectional effect on the primary endpoint and the positive interaction between age and thrombectomy treatment effect warranted further investigation.

The RESILIENT-Extend trial was sponsored by the Brazilian Ministry of Health.
 

A version of this article appeared on Medscape.com.

PHOENIX — Thrombectomy is generally beneficial for patients from a low-income population who have a large vessel occlusion stroke presenting in the later time window and who can be identified as suitable for treatment without the need for advanced and costly imaging, a new Brazilian trial has shown.

“The RESILIENT-Extend trial is the first major study of thrombectomy in the late time window (8-24 h) conducted outside first-world countries and shows the procedure also has benefit in a lower socioeconomic status population without the need for costly imaging equipment,” said lead investigator Raul G. Nogueira, MD. 

“The trial expands the treatment window for thrombectomy globally with simplified selection criteria based on non-contrast CT, potentially altering current guidelines,” Dr. Nogueira said.

However, there were some caveats that need to be considered; in particular, a lack of benefit with thrombectomy in older patients (over 68 years of age), which Dr. Nogueira believes is a reflection of the particular population enrolled in this study. Specifically, he suggested that older age in this low socioeconomic status population is a surrogate for frailty, and the study may have identified frailty as a factor that correlates with reduced or lack of benefit of thrombectomy.

Dr. Nogueira, who is a professor of neurology and neurosurgery at the University of Pittsburgh, and Sheila Martins, MD, a professor of neurology at Hospital de Clinicas Porto Alegre in Brazil, presented the RESILIENT-Extend results at the International Stroke Conference presented by the American Stroke Association, a division of the American Heart Association.

Dr. Nogueira explained that the lack of available advanced imaging techniques is a major challenge for implementing endovascular therapy in an extended time window, especially in lower-income countries.

“Our main objective was to see if we could remove the need for advanced imaging to select patients with large vessel occlusion stroke in the late time window (8-24 h) for thrombectomy,” he said. “In this way, our trial overlaps somewhat with the MR CLEAN-LATE Trial conducted in the Netherlands, although the two trials were conducted in very different socioeconomic populations.”

The RESILIENT-Extend trial was conducted in the public health service of Brazil and involved a different population of people than have been included in other thrombectomy trials, which have mostly been conducted in first-world countries.

“The public health system in Brazil is not well-resourced and tends to care for patients at lower socioeconomic levels. These patients are fundamentally different from the average patients in the first-world recruited into most other thrombectomy trials,” Dr. Nogueira noted.

The trial enrolled 245 patients with a large vessel occlusion stroke within 8-24 hours of last known well. Patients were included who had a mismatch between the clinical severity as shown by the National Institutes of Health Stroke Scale (NIHSS) score and the stroke burden on imaging as measured by ASPECTS scores.

They had to have relatively high NIHSS scores (8 or more) showing more severe strokes but also a high ASPECTS score (5-10) excluding patients with large areas of ischemic brain. There was also a sliding scale that adjusted for age to avoid enrolling elderly patients with large strokes.

These patients were identified exclusively using non-contrast CT and CT angiography imaging.

The median age of patients included was 62-63 years. Dr. Nogueira pointed out that patients were slightly younger than seen in other thrombectomy trials, perhaps because in lower-middle-income countries strokes occur at a younger age. They also have a higher case fatality rate.

The median baseline NIHSS score was 16, and the median ASPECTS score was 7-8.

The median time to treatment was 12.5 hours, which is similar to other late window thrombectomy trials.
 

Conflicting Results on Shift Analysis

The primary outcome was a shift analysis of the modified Rankin Scale (mRS) disability score at 90 days.

This showed a bidirectional result, with thrombectomy increasing the chances of a good or excellent outcome (mRS, 0-3), but there was also a nonsignificant increased risk for a bad outcome (mRS, 5-6).

“This bidirectional result prevents a common odds ratio from being calculated, so the primary endpoint is not applicable,” Dr. Nogueira reported.

The researchers therefore used the secondary outcomes as the main results of the study.

These showed that the number of patients achieving a good outcome (mRS, 0-2) was significantly increased with thrombectomy (25% vs. 14%, adjusted odds ratio, 2.56; P = .012).

The number of patients achieving an excellent outcome (mRS, 0-1) was also significantly increased.

But these increases in good outcomes came at the cost of some patients having an increased risk for severe disability or death (mRS, 5-6).

The odds ratio for an mRS of 0-4 versus 5-6 was 0.71, and for an mRS of 0-5 versus 6, the odds ratio was 0.58. Both these results were nonsignificant.

Another anomaly in the RESILIENT-Extend trial was the observation of no benefit of thrombectomy seen in older patients.

“In general, trials of thrombectomy in the first world have shown a greater treatment effect in older patients, but this was not seen in our trial, where older patients (over 68 years) did not derive any benefit from the procedure,” Dr. Nogueira noted.

A similar observation was also seen in the first RESILIENT trial in patients treated within 8 hours of stroke onset, which was also conducted in Brazil, leading to the suggestion that it is related to the patient population included.

“In the Brazilian public health service, older patients are very vulnerable and frail. They are different to older patients in first world countries. It appears they may be too fragile to withstand the thrombectomy process,” Dr. Nogueira said.
 

Frailty: A Ceiling Effect?

Results from the two RESILIENT trials give a word of caution to the thrombectomy field, Dr. Nogueira said.

“This procedure was initially thought suitable only for patients with small core strokes, but we now have a series of trials showing benefit of thrombectomy in large core strokes as well,” Dr. Nogueira said. “We have started to believe that this intervention will benefit almost all patients with large vessel occlusion stroke everywhere around the world, but our data suggest that we have to consider the specific populations that we are serving and that factors such as socioeconomic status and frailty have to be taken into account.

“Both the RESILIENT trials have shown that thrombectomy does not appear to be suitable for older patients, over 68-70 years of age, in the public health service in Brazil,” he noted. “In this population, a patient aged 70 can be quite different to a patient of the same age in a first-world country. I think in our population, an age of over 68-70 is a surrogate for frailty, which will not be the case in first-world countries. In this regard, I think we have found a ceiling effect for benefit of thrombectomy, which is frailty.”

Dr. Nogueira speculated that the bidirectional effect on the mRS shift analysis may also have been caused by the frailty of some of the patients.

“What the results may be showing is that for most of the population, there is a benefit of thrombectomy, but for some patients, possibly the most frail, then the procedure can be too overwhelming for them. But the suggestion of harm was not significant, so this observation could have also just been the play of chance,” he added.
 

Interpreting the Findings

Commenting on the RESILIENT-Extend study results, Michael Hill, MD, professor of neurology at the University of Calgary, Canada, pointed out that there was an absolute benefit of 11.1% on the mRS of 0-2 outcome but a similar signal of harm, with a 10.2% increase in mortality in the thrombectomy group, although that was not statistically significant.

“This signal of harm appears not to be due to an increase in intracranial hemorrhage or procedural mishap,” he said. “It is unclear why there were more deaths; the overall trial numbers are small enough that this could be a chance finding.”

Dr. Hill also noted that the absolute proportion of patients achieving an independent functional outcome was 50% less than in the DAWN trial of thrombectomy in the extended window. “This tells us that the patients selected for inclusion into RESILIENT-Extend were physiologically different from those in DAWN,” he said.

Also commenting on the study, Amrou Sarraj, MD, professor of neurology at University Hospitals Cleveland Medical Center–Case Western Reserve University in Cleveland, said: “The RESILIENT-Extend investigators should be congratulated for the successful conduct of the trial and providing evidence of benefit of thrombectomy procedure with simplified neuroimaging protocol using CT and CTA in resource-limited settings. These findings will help support extending the access to thrombectomy in areas without availability of advanced imaging.”

He said the bidirectional effect on the primary endpoint and the positive interaction between age and thrombectomy treatment effect warranted further investigation.

The RESILIENT-Extend trial was sponsored by the Brazilian Ministry of Health.
 

A version of this article appeared on Medscape.com.

PHOENIX — Thrombectomy is generally beneficial for patients from a low-income population who have a large vessel occlusion stroke presenting in the later time window and who can be identified as suitable for treatment without the need for advanced and costly imaging, a new Brazilian trial has shown.

“The RESILIENT-Extend trial is the first major study of thrombectomy in the late time window (8-24 h) conducted outside first-world countries and shows the procedure also has benefit in a lower socioeconomic status population without the need for costly imaging equipment,” said lead investigator Raul G. Nogueira, MD. 

“The trial expands the treatment window for thrombectomy globally with simplified selection criteria based on non-contrast CT, potentially altering current guidelines,” Dr. Nogueira said.

However, there were some caveats that need to be considered; in particular, a lack of benefit with thrombectomy in older patients (over 68 years of age), which Dr. Nogueira believes is a reflection of the particular population enrolled in this study. Specifically, he suggested that older age in this low socioeconomic status population is a surrogate for frailty, and the study may have identified frailty as a factor that correlates with reduced or lack of benefit of thrombectomy.

Dr. Nogueira, who is a professor of neurology and neurosurgery at the University of Pittsburgh, and Sheila Martins, MD, a professor of neurology at Hospital de Clinicas Porto Alegre in Brazil, presented the RESILIENT-Extend results at the International Stroke Conference presented by the American Stroke Association, a division of the American Heart Association.

Dr. Nogueira explained that the lack of available advanced imaging techniques is a major challenge for implementing endovascular therapy in an extended time window, especially in lower-income countries.

“Our main objective was to see if we could remove the need for advanced imaging to select patients with large vessel occlusion stroke in the late time window (8-24 h) for thrombectomy,” he said. “In this way, our trial overlaps somewhat with the MR CLEAN-LATE Trial conducted in the Netherlands, although the two trials were conducted in very different socioeconomic populations.”

The RESILIENT-Extend trial was conducted in the public health service of Brazil and involved a different population of people than have been included in other thrombectomy trials, which have mostly been conducted in first-world countries.

“The public health system in Brazil is not well-resourced and tends to care for patients at lower socioeconomic levels. These patients are fundamentally different from the average patients in the first-world recruited into most other thrombectomy trials,” Dr. Nogueira noted.

The trial enrolled 245 patients with a large vessel occlusion stroke within 8-24 hours of last known well. Patients were included who had a mismatch between the clinical severity as shown by the National Institutes of Health Stroke Scale (NIHSS) score and the stroke burden on imaging as measured by ASPECTS scores.

They had to have relatively high NIHSS scores (8 or more) showing more severe strokes but also a high ASPECTS score (5-10) excluding patients with large areas of ischemic brain. There was also a sliding scale that adjusted for age to avoid enrolling elderly patients with large strokes.

These patients were identified exclusively using non-contrast CT and CT angiography imaging.

The median age of patients included was 62-63 years. Dr. Nogueira pointed out that patients were slightly younger than seen in other thrombectomy trials, perhaps because in lower-middle-income countries strokes occur at a younger age. They also have a higher case fatality rate.

The median baseline NIHSS score was 16, and the median ASPECTS score was 7-8.

The median time to treatment was 12.5 hours, which is similar to other late window thrombectomy trials.
 

Conflicting Results on Shift Analysis

The primary outcome was a shift analysis of the modified Rankin Scale (mRS) disability score at 90 days.

This showed a bidirectional result, with thrombectomy increasing the chances of a good or excellent outcome (mRS, 0-3), but there was also a nonsignificant increased risk for a bad outcome (mRS, 5-6).

“This bidirectional result prevents a common odds ratio from being calculated, so the primary endpoint is not applicable,” Dr. Nogueira reported.

The researchers therefore used the secondary outcomes as the main results of the study.

These showed that the number of patients achieving a good outcome (mRS, 0-2) was significantly increased with thrombectomy (25% vs. 14%, adjusted odds ratio, 2.56; P = .012).

The number of patients achieving an excellent outcome (mRS, 0-1) was also significantly increased.

But these increases in good outcomes came at the cost of some patients having an increased risk for severe disability or death (mRS, 5-6).

The odds ratio for an mRS of 0-4 versus 5-6 was 0.71, and for an mRS of 0-5 versus 6, the odds ratio was 0.58. Both these results were nonsignificant.

Another anomaly in the RESILIENT-Extend trial was the observation of no benefit of thrombectomy seen in older patients.

“In general, trials of thrombectomy in the first world have shown a greater treatment effect in older patients, but this was not seen in our trial, where older patients (over 68 years) did not derive any benefit from the procedure,” Dr. Nogueira noted.

A similar observation was also seen in the first RESILIENT trial in patients treated within 8 hours of stroke onset, which was also conducted in Brazil, leading to the suggestion that it is related to the patient population included.

“In the Brazilian public health service, older patients are very vulnerable and frail. They are different to older patients in first world countries. It appears they may be too fragile to withstand the thrombectomy process,” Dr. Nogueira said.
 

Frailty: A Ceiling Effect?

Results from the two RESILIENT trials give a word of caution to the thrombectomy field, Dr. Nogueira said.

“This procedure was initially thought suitable only for patients with small core strokes, but we now have a series of trials showing benefit of thrombectomy in large core strokes as well,” Dr. Nogueira said. “We have started to believe that this intervention will benefit almost all patients with large vessel occlusion stroke everywhere around the world, but our data suggest that we have to consider the specific populations that we are serving and that factors such as socioeconomic status and frailty have to be taken into account.

“Both the RESILIENT trials have shown that thrombectomy does not appear to be suitable for older patients, over 68-70 years of age, in the public health service in Brazil,” he noted. “In this population, a patient aged 70 can be quite different to a patient of the same age in a first-world country. I think in our population, an age of over 68-70 is a surrogate for frailty, which will not be the case in first-world countries. In this regard, I think we have found a ceiling effect for benefit of thrombectomy, which is frailty.”

Dr. Nogueira speculated that the bidirectional effect on the mRS shift analysis may also have been caused by the frailty of some of the patients.

“What the results may be showing is that for most of the population, there is a benefit of thrombectomy, but for some patients, possibly the most frail, then the procedure can be too overwhelming for them. But the suggestion of harm was not significant, so this observation could have also just been the play of chance,” he added.
 

Interpreting the Findings

Commenting on the RESILIENT-Extend study results, Michael Hill, MD, professor of neurology at the University of Calgary, Canada, pointed out that there was an absolute benefit of 11.1% on the mRS of 0-2 outcome but a similar signal of harm, with a 10.2% increase in mortality in the thrombectomy group, although that was not statistically significant.

“This signal of harm appears not to be due to an increase in intracranial hemorrhage or procedural mishap,” he said. “It is unclear why there were more deaths; the overall trial numbers are small enough that this could be a chance finding.”

Dr. Hill also noted that the absolute proportion of patients achieving an independent functional outcome was 50% less than in the DAWN trial of thrombectomy in the extended window. “This tells us that the patients selected for inclusion into RESILIENT-Extend were physiologically different from those in DAWN,” he said.

Also commenting on the study, Amrou Sarraj, MD, professor of neurology at University Hospitals Cleveland Medical Center–Case Western Reserve University in Cleveland, said: “The RESILIENT-Extend investigators should be congratulated for the successful conduct of the trial and providing evidence of benefit of thrombectomy procedure with simplified neuroimaging protocol using CT and CTA in resource-limited settings. These findings will help support extending the access to thrombectomy in areas without availability of advanced imaging.”

He said the bidirectional effect on the primary endpoint and the positive interaction between age and thrombectomy treatment effect warranted further investigation.

The RESILIENT-Extend trial was sponsored by the Brazilian Ministry of Health.
 

A version of this article appeared on Medscape.com.

PHOENIX — Black women who develop high blood pressure before age 35 have a threefold increased risk of having a midlife stroke, new observational data suggest. The Black Women’s Health Study, which has followed 59,000 participants in the United States since 1990s, also showed that those who develop hypertension before age 45 have twice the risk of suffering a stroke.

“The really concerning thing about this data is the high proportion of young Black women who had high blood pressure and are suffering strokes relatively early in life,” said the study’s lead author, Hugo J. Aparicio, MD, associate professor of neurology at Boston University Chobanian & Avedisian School of Medicine, Boston. “This can lead to a burden of disability in relatively young women who may be at the prime of their life, pursuing careers, and looking after family.”

Dr. Aparicio presented the data at the International Stroke Conference presented by the American Stroke Association, a division of the American Heart Association.

He explained that while there has been good progress in reducing stroke rates in older people over the past decades, there is a concerning observation from multiple datasets showing that stroke rates in midlife have been plateauing or even increasing in recent years.

“For Black women specifically, there is a concern, as we know this group has higher rates of raised blood pressure and stroke overall,” said Dr. Aparicio. “We were interested in looking at whether the onset of hypertension at an earlier age in this group is one of the reasons for the increased stroke risk in midlife.”
 

A Large Study Cohort

The researchers analyzed data from the Black Women’s Health Study; the baseline year for this analysis, which included 46,754 stroke-free participants younger than age 65 (mean age, 42 years), was the 1999 questionnaire.

Both history of hypertension — defined as physician-diagnosed hypertension with the use of an antihypertensive medication — and stroke occurrence were determined by self-report. It has been shown in previous studies that these self-reported data on incidence of hypertension in this dataset are highly reliable, Dr. Aparicio noted.

At baseline, 10.5% of participants aged 45-64 years had hypertension. Stroke occurred in 3.2% of individuals over a mean follow-up of 17 years.

Black women with hypertension before age 45 had a higher risk for midlife stroke (hazard ratio [HR], 2.23; 95% confidence interval [CI], 1.79-2.78), after adjustment for age, neighborhood socioeconomic status, residence in the Stroke Belt, smoking, body mass index, and diabetes than women with no history of hypertension.

The risk was also increased with hypertension at midlife ages 45-64 years (HR, 1.69; 95% CI, 1.47-1.95) and was highest among those with hypertension at ages 24-34 years (HR, 3.15; 95% CI, 1.92-5.16).

“Our results show that among young Black women, those with hypertension have a much higher stroke risk than those without hypertension, even if they are taking antihypertensive medication,” Dr. Aparicio said. “This underscores how potent hypertension is as a risk factor for stroke.”

He concluded that both individuals and doctors need to realize that hypertension and stroke are not problems of the elderly exclusively.

“These are conditions that need to be addressed very early in life. This is even more important for Black women, as they are a high-risk group. They need to pay attention to blood pressure numbers early in life — ideally from adolescence — to catch levels before they become too elevated,” Dr. Aparicio said.

“We also need to address lifestyle changes including diet, physical activity, sleep habits, and address other cardiovascular risk factors such as cholesterol and body mass index, so we can prevent strokes from occurring,” he added. “At the policy level, we need to advocate, provide and fund primary prevention measures, and enable earlier screening and better treatment.”
 

The Role of Psychosocial Stressors

Commenting on the study, the American Heart Association immediate past president, Michelle A. Albert, MD, professor of medicine at the University of California, San Francisco, emphasized the importance of regular primary care appointments to screen for high blood pressure and other cardiovascular risk factors.

She pointed out that one of the contributing factors that may increase the risk for Black women is their disproportionate experience of psychosocial stressors and chronic cumulative stress.

This could include stress related to financial issues, racism and other forms of bias, the neighborhood environment, and having to take care of multiple generations of family with limited resources.

“These are some of the things that are less talked about as going into the heightened risk for many cardiovascular risk factors, including hypertension, very early in life for Black women that we need to bring to the forefront of conversations,” Dr. Albert said.

“These stressors not only impact hypertension onset but also they impact one’s ability to be able to seek help, and once the help is sought, to be able to sustain the therapies recommended and the interventions recommended,” she added.

The authors reported no relevant disclosures.
 

A version of this article appeared on Medscape.com.

PHOENIX — Black women who develop high blood pressure before age 35 have a threefold increased risk of having a midlife stroke, new observational data suggest. The Black Women’s Health Study, which has followed 59,000 participants in the United States since 1990s, also showed that those who develop hypertension before age 45 have twice the risk of suffering a stroke.

“The really concerning thing about this data is the high proportion of young Black women who had high blood pressure and are suffering strokes relatively early in life,” said the study’s lead author, Hugo J. Aparicio, MD, associate professor of neurology at Boston University Chobanian & Avedisian School of Medicine, Boston. “This can lead to a burden of disability in relatively young women who may be at the prime of their life, pursuing careers, and looking after family.”

Dr. Aparicio presented the data at the International Stroke Conference presented by the American Stroke Association, a division of the American Heart Association.

He explained that while there has been good progress in reducing stroke rates in older people over the past decades, there is a concerning observation from multiple datasets showing that stroke rates in midlife have been plateauing or even increasing in recent years.

“For Black women specifically, there is a concern, as we know this group has higher rates of raised blood pressure and stroke overall,” said Dr. Aparicio. “We were interested in looking at whether the onset of hypertension at an earlier age in this group is one of the reasons for the increased stroke risk in midlife.”
 

A Large Study Cohort

The researchers analyzed data from the Black Women’s Health Study; the baseline year for this analysis, which included 46,754 stroke-free participants younger than age 65 (mean age, 42 years), was the 1999 questionnaire.

Both history of hypertension — defined as physician-diagnosed hypertension with the use of an antihypertensive medication — and stroke occurrence were determined by self-report. It has been shown in previous studies that these self-reported data on incidence of hypertension in this dataset are highly reliable, Dr. Aparicio noted.

At baseline, 10.5% of participants aged 45-64 years had hypertension. Stroke occurred in 3.2% of individuals over a mean follow-up of 17 years.

Black women with hypertension before age 45 had a higher risk for midlife stroke (hazard ratio [HR], 2.23; 95% confidence interval [CI], 1.79-2.78), after adjustment for age, neighborhood socioeconomic status, residence in the Stroke Belt, smoking, body mass index, and diabetes than women with no history of hypertension.

The risk was also increased with hypertension at midlife ages 45-64 years (HR, 1.69; 95% CI, 1.47-1.95) and was highest among those with hypertension at ages 24-34 years (HR, 3.15; 95% CI, 1.92-5.16).

“Our results show that among young Black women, those with hypertension have a much higher stroke risk than those without hypertension, even if they are taking antihypertensive medication,” Dr. Aparicio said. “This underscores how potent hypertension is as a risk factor for stroke.”

He concluded that both individuals and doctors need to realize that hypertension and stroke are not problems of the elderly exclusively.

“These are conditions that need to be addressed very early in life. This is even more important for Black women, as they are a high-risk group. They need to pay attention to blood pressure numbers early in life — ideally from adolescence — to catch levels before they become too elevated,” Dr. Aparicio said.

“We also need to address lifestyle changes including diet, physical activity, sleep habits, and address other cardiovascular risk factors such as cholesterol and body mass index, so we can prevent strokes from occurring,” he added. “At the policy level, we need to advocate, provide and fund primary prevention measures, and enable earlier screening and better treatment.”
 

The Role of Psychosocial Stressors

Commenting on the study, the American Heart Association immediate past president, Michelle A. Albert, MD, professor of medicine at the University of California, San Francisco, emphasized the importance of regular primary care appointments to screen for high blood pressure and other cardiovascular risk factors.

She pointed out that one of the contributing factors that may increase the risk for Black women is their disproportionate experience of psychosocial stressors and chronic cumulative stress.

This could include stress related to financial issues, racism and other forms of bias, the neighborhood environment, and having to take care of multiple generations of family with limited resources.

“These are some of the things that are less talked about as going into the heightened risk for many cardiovascular risk factors, including hypertension, very early in life for Black women that we need to bring to the forefront of conversations,” Dr. Albert said.

“These stressors not only impact hypertension onset but also they impact one’s ability to be able to seek help, and once the help is sought, to be able to sustain the therapies recommended and the interventions recommended,” she added.

The authors reported no relevant disclosures.
 

A version of this article appeared on Medscape.com.

PHOENIX — Black women who develop high blood pressure before age 35 have a threefold increased risk of having a midlife stroke, new observational data suggest. The Black Women’s Health Study, which has followed 59,000 participants in the United States since 1990s, also showed that those who develop hypertension before age 45 have twice the risk of suffering a stroke.

“The really concerning thing about this data is the high proportion of young Black women who had high blood pressure and are suffering strokes relatively early in life,” said the study’s lead author, Hugo J. Aparicio, MD, associate professor of neurology at Boston University Chobanian & Avedisian School of Medicine, Boston. “This can lead to a burden of disability in relatively young women who may be at the prime of their life, pursuing careers, and looking after family.”

Dr. Aparicio presented the data at the International Stroke Conference presented by the American Stroke Association, a division of the American Heart Association.

He explained that while there has been good progress in reducing stroke rates in older people over the past decades, there is a concerning observation from multiple datasets showing that stroke rates in midlife have been plateauing or even increasing in recent years.

“For Black women specifically, there is a concern, as we know this group has higher rates of raised blood pressure and stroke overall,” said Dr. Aparicio. “We were interested in looking at whether the onset of hypertension at an earlier age in this group is one of the reasons for the increased stroke risk in midlife.”
 

A Large Study Cohort

The researchers analyzed data from the Black Women’s Health Study; the baseline year for this analysis, which included 46,754 stroke-free participants younger than age 65 (mean age, 42 years), was the 1999 questionnaire.

Both history of hypertension — defined as physician-diagnosed hypertension with the use of an antihypertensive medication — and stroke occurrence were determined by self-report. It has been shown in previous studies that these self-reported data on incidence of hypertension in this dataset are highly reliable, Dr. Aparicio noted.

At baseline, 10.5% of participants aged 45-64 years had hypertension. Stroke occurred in 3.2% of individuals over a mean follow-up of 17 years.

Black women with hypertension before age 45 had a higher risk for midlife stroke (hazard ratio [HR], 2.23; 95% confidence interval [CI], 1.79-2.78), after adjustment for age, neighborhood socioeconomic status, residence in the Stroke Belt, smoking, body mass index, and diabetes than women with no history of hypertension.

The risk was also increased with hypertension at midlife ages 45-64 years (HR, 1.69; 95% CI, 1.47-1.95) and was highest among those with hypertension at ages 24-34 years (HR, 3.15; 95% CI, 1.92-5.16).

“Our results show that among young Black women, those with hypertension have a much higher stroke risk than those without hypertension, even if they are taking antihypertensive medication,” Dr. Aparicio said. “This underscores how potent hypertension is as a risk factor for stroke.”

He concluded that both individuals and doctors need to realize that hypertension and stroke are not problems of the elderly exclusively.

“These are conditions that need to be addressed very early in life. This is even more important for Black women, as they are a high-risk group. They need to pay attention to blood pressure numbers early in life — ideally from adolescence — to catch levels before they become too elevated,” Dr. Aparicio said.

“We also need to address lifestyle changes including diet, physical activity, sleep habits, and address other cardiovascular risk factors such as cholesterol and body mass index, so we can prevent strokes from occurring,” he added. “At the policy level, we need to advocate, provide and fund primary prevention measures, and enable earlier screening and better treatment.”
 

The Role of Psychosocial Stressors

Commenting on the study, the American Heart Association immediate past president, Michelle A. Albert, MD, professor of medicine at the University of California, San Francisco, emphasized the importance of regular primary care appointments to screen for high blood pressure and other cardiovascular risk factors.

She pointed out that one of the contributing factors that may increase the risk for Black women is their disproportionate experience of psychosocial stressors and chronic cumulative stress.

This could include stress related to financial issues, racism and other forms of bias, the neighborhood environment, and having to take care of multiple generations of family with limited resources.

“These are some of the things that are less talked about as going into the heightened risk for many cardiovascular risk factors, including hypertension, very early in life for Black women that we need to bring to the forefront of conversations,” Dr. Albert said.

“These stressors not only impact hypertension onset but also they impact one’s ability to be able to seek help, and once the help is sought, to be able to sustain the therapies recommended and the interventions recommended,” she added.

The authors reported no relevant disclosures.
 

A version of this article appeared on Medscape.com.

Complications during pregnancy may be a wake-up call pointing to a higher risk for cardiovascular (CVD) and other diseases later in life. Therefore, the postpartum and interpregnancy periods are opportune windows for reducing CVD susceptibility and providing preventive care, especially for mothers with a history of adverse pregnancy outcomes (APOs). To that end, the American Heart Association recently released a scientific statement in Circulation outlining pregnancy-related CVD risks and reviewing evidence for preventive lifestyle strategies based on the AHA’s Life’s Essential 8 recommendations.

The Life’s Essential 8 encompass healthy eating, sleeping, and activity patterns; controlling weight, blood pressure, cholesterol, and blood sugar; and avoiding tobacco use.

“The motivation behind this statement was that complications in pregnancy are becoming more common and we now have more understanding that these serve as important risk factors for heart disease later in life,” said Jennifer Lewey, MD, MPH, director of the Penn Women’s Cardiovascular Health Program and an assistant professor of medicine at the University of Pennsylvania Perelman School of Medicine in Philadelphia.

Perelman School of Medicine

“These risk factors are underrecognized and underappreciated. Clinicians don’t feel comfortable counseling their patients about how to reduce their cardiovascular disease risk,” Dr. Lewey, chair of the AHA writing group, said in an interview.

“So we thought this was the perfect time to highlight what we know and don’t know about how to care for this population,” she said.

APOs predispose mothers to heart disease and other long-term complications, including heart failure, stroke, chronic kidney disease, and vascular dementia. “Pregnancy is a significant stress on the body, and APOs such as preeclampsia can lead to vascular changes in the blood vessels and structural changes to the heart that can persist long term,” Dr. Lewey explained. Reduced maternal physical activity and unshed weight can compound the problem.

Varying by race and ethnicity, the proportion of mothers experiencing pregnancy complications, such as high blood pressure, gestational diabetes, and/or preterm birth is estimated at 10%-20%, the statement authors noted. These complications may serve as a wake-up call to young mothers.

The AHA panel believes that identifying at-risk women at younger ages will enable prevention through lifestyle changes and timely treatment. Little is known, however about what specific care may best reduce long-term CVD risk in women who had pregnancy complications, Dr. Lewey said. While randomized clinical trials have yet to evaluate the effects of postpartum interventions on CVD outcomes, the need for strategies supported by rigorous evidence is clear. “In particular, the fourth trimester, defined as the 12 weeks after delivery, is an optimal time to engage postpartum individuals in care to reduce maternal morbidity and improve care transitions,” the AHA group wrote.

An earlier AHA statement in 2021 recommended frequent cardiac risk factor screening in the first year postpartum at 6 and 12 weeks and again at 6 and 12 months, with appropriate transition from postpartum to longitudinal primary care around the 8- to 12-week mark.

Among the current statement’s findings: High blood pressure is the most prevalent cardiovascular condition during pregnancy, and the last two decades have seen a 25% increase in preeclampsia.

Hypertension during pregnancy carries a two- to fourfold higher risk of chronic hypertension within 2-7 years.

Women with one or more APOs experience heart attack and stroke at younger ages. Commenting on the statement but not involved in it, internist Natalie A. Cameron, MD, a primary and preventive care physician at Northwestern Medicine in Chicago, said, “This statement will be very helpful for physicians from a primary care perspective, especially since in internal medicine we don’t standardly receive education in cardiovascular health in the context of pregnancy and the first year postpartum.”

Northwestern Medicine

Complications during pregnancy may be a wake-up call pointing to a higher risk for cardiovascular (CVD) and other diseases later in life. Therefore, the postpartum and interpregnancy periods are opportune windows for reducing CVD susceptibility and providing preventive care, especially for mothers with a history of adverse pregnancy outcomes (APOs). To that end, the American Heart Association recently released a scientific statement in Circulation outlining pregnancy-related CVD risks and reviewing evidence for preventive lifestyle strategies based on the AHA’s Life’s Essential 8 recommendations.

The Life’s Essential 8 encompass healthy eating, sleeping, and activity patterns; controlling weight, blood pressure, cholesterol, and blood sugar; and avoiding tobacco use.

“The motivation behind this statement was that complications in pregnancy are becoming more common and we now have more understanding that these serve as important risk factors for heart disease later in life,” said Jennifer Lewey, MD, MPH, director of the Penn Women’s Cardiovascular Health Program and an assistant professor of medicine at the University of Pennsylvania Perelman School of Medicine in Philadelphia.

Perelman School of Medicine

“These risk factors are underrecognized and underappreciated. Clinicians don’t feel comfortable counseling their patients about how to reduce their cardiovascular disease risk,” Dr. Lewey, chair of the AHA writing group, said in an interview.

“So we thought this was the perfect time to highlight what we know and don’t know about how to care for this population,” she said.

APOs predispose mothers to heart disease and other long-term complications, including heart failure, stroke, chronic kidney disease, and vascular dementia. “Pregnancy is a significant stress on the body, and APOs such as preeclampsia can lead to vascular changes in the blood vessels and structural changes to the heart that can persist long term,” Dr. Lewey explained. Reduced maternal physical activity and unshed weight can compound the problem.

Varying by race and ethnicity, the proportion of mothers experiencing pregnancy complications, such as high blood pressure, gestational diabetes, and/or preterm birth is estimated at 10%-20%, the statement authors noted. These complications may serve as a wake-up call to young mothers.

The AHA panel believes that identifying at-risk women at younger ages will enable prevention through lifestyle changes and timely treatment. Little is known, however about what specific care may best reduce long-term CVD risk in women who had pregnancy complications, Dr. Lewey said. While randomized clinical trials have yet to evaluate the effects of postpartum interventions on CVD outcomes, the need for strategies supported by rigorous evidence is clear. “In particular, the fourth trimester, defined as the 12 weeks after delivery, is an optimal time to engage postpartum individuals in care to reduce maternal morbidity and improve care transitions,” the AHA group wrote.

An earlier AHA statement in 2021 recommended frequent cardiac risk factor screening in the first year postpartum at 6 and 12 weeks and again at 6 and 12 months, with appropriate transition from postpartum to longitudinal primary care around the 8- to 12-week mark.

Among the current statement’s findings: High blood pressure is the most prevalent cardiovascular condition during pregnancy, and the last two decades have seen a 25% increase in preeclampsia.

Hypertension during pregnancy carries a two- to fourfold higher risk of chronic hypertension within 2-7 years.

Women with one or more APOs experience heart attack and stroke at younger ages. Commenting on the statement but not involved in it, internist Natalie A. Cameron, MD, a primary and preventive care physician at Northwestern Medicine in Chicago, said, “This statement will be very helpful for physicians from a primary care perspective, especially since in internal medicine we don’t standardly receive education in cardiovascular health in the context of pregnancy and the first year postpartum.”

Northwestern Medicine

Complications during pregnancy may be a wake-up call pointing to a higher risk for cardiovascular (CVD) and other diseases later in life. Therefore, the postpartum and interpregnancy periods are opportune windows for reducing CVD susceptibility and providing preventive care, especially for mothers with a history of adverse pregnancy outcomes (APOs). To that end, the American Heart Association recently released a scientific statement in Circulation outlining pregnancy-related CVD risks and reviewing evidence for preventive lifestyle strategies based on the AHA’s Life’s Essential 8 recommendations.

The Life’s Essential 8 encompass healthy eating, sleeping, and activity patterns; controlling weight, blood pressure, cholesterol, and blood sugar; and avoiding tobacco use.

“The motivation behind this statement was that complications in pregnancy are becoming more common and we now have more understanding that these serve as important risk factors for heart disease later in life,” said Jennifer Lewey, MD, MPH, director of the Penn Women’s Cardiovascular Health Program and an assistant professor of medicine at the University of Pennsylvania Perelman School of Medicine in Philadelphia.

Perelman School of Medicine

“These risk factors are underrecognized and underappreciated. Clinicians don’t feel comfortable counseling their patients about how to reduce their cardiovascular disease risk,” Dr. Lewey, chair of the AHA writing group, said in an interview.

“So we thought this was the perfect time to highlight what we know and don’t know about how to care for this population,” she said.

APOs predispose mothers to heart disease and other long-term complications, including heart failure, stroke, chronic kidney disease, and vascular dementia. “Pregnancy is a significant stress on the body, and APOs such as preeclampsia can lead to vascular changes in the blood vessels and structural changes to the heart that can persist long term,” Dr. Lewey explained. Reduced maternal physical activity and unshed weight can compound the problem.

Varying by race and ethnicity, the proportion of mothers experiencing pregnancy complications, such as high blood pressure, gestational diabetes, and/or preterm birth is estimated at 10%-20%, the statement authors noted. These complications may serve as a wake-up call to young mothers.

The AHA panel believes that identifying at-risk women at younger ages will enable prevention through lifestyle changes and timely treatment. Little is known, however about what specific care may best reduce long-term CVD risk in women who had pregnancy complications, Dr. Lewey said. While randomized clinical trials have yet to evaluate the effects of postpartum interventions on CVD outcomes, the need for strategies supported by rigorous evidence is clear. “In particular, the fourth trimester, defined as the 12 weeks after delivery, is an optimal time to engage postpartum individuals in care to reduce maternal morbidity and improve care transitions,” the AHA group wrote.

An earlier AHA statement in 2021 recommended frequent cardiac risk factor screening in the first year postpartum at 6 and 12 weeks and again at 6 and 12 months, with appropriate transition from postpartum to longitudinal primary care around the 8- to 12-week mark.

Among the current statement’s findings: High blood pressure is the most prevalent cardiovascular condition during pregnancy, and the last two decades have seen a 25% increase in preeclampsia.

Hypertension during pregnancy carries a two- to fourfold higher risk of chronic hypertension within 2-7 years.

Women with one or more APOs experience heart attack and stroke at younger ages. Commenting on the statement but not involved in it, internist Natalie A. Cameron, MD, a primary and preventive care physician at Northwestern Medicine in Chicago, said, “This statement will be very helpful for physicians from a primary care perspective, especially since in internal medicine we don’t standardly receive education in cardiovascular health in the context of pregnancy and the first year postpartum.”

Northwestern Medicine

Intravenous (IV) administration of the antiplatelet agent tirofiban for 72 hours was associated with a reduction in early neurologic deterioration compared with oral aspirin therapy in patients with acute ischemic stroke, in the randomized TREND trial.

The results were presented at the International Stroke Conference 2024, held on February 7-9 in Phoenix, Arizona.

Lead author Zhao Wenbo, MD, Xuanwu Hospital, Beijing, China, noted that neurologic deterioration, characterized by a sudden onset and quick peak of neurologic deficits, is a common phenomenon in acute ischemic stroke and is strongly associated with poor clinical outcomes.

Ischemic stroke progression is the main cause of neurologic deterioration, especially during the first few days after onset, Dr. Wenbo said. Several clinical studies have found that intensive antiplatelet therapy may prevent early neurologic deterioration and improve functional outcomes, but administering oral antiplatelet agents can be difficult because of dysphagia, he reported.

The TREND trial was conducted to investigate whether IV tirofiban could prevent early neurologic deterioration without increasing the risk for symptomatic intracerebral hemorrhage in acute ischemic stroke.

The study included 426 patients with acute ischemic stroke within 24 hours of symptom onset who had a neurologic deficit attributed to focal cerebral ischemia and a National Institutes of Health Stroke Scale (NIHSS) score between 4 and 20 points and who were not treated with thrombolysis or endovascular thrombectomy. Patients with cardioembolic stroke were also excluded.

Patients were a median of 10-12 hours from symptom onset and had a baseline NIHSS score of 5.

They were randomized to IV tirofiban or oral aspirin for 72 hours. All patients were then continued on oral antiplatelet therapy.

The primary efficacy outcome was neurologic deterioration within 72 hours after randomization, defined as an increase in NIHSS score of 4 points or more.

This occurred in nine patients (4.2%) in the tirofiban group vs 28 (13.2%) in the control group (relative risk, 0.32; 95% CI, 0.15-0.66; P = .002).

A consistent benefit of IV tirofiban was seen across all subgroups.

The secondary endpoint of neurologic deterioration within 72 hours after randomization, defined as an increase of NIHSS score of 2 points or more, was also significantly reduced. This occurred in 11.7% of the tirofiban group vs 23.6% of the aspirin group (RR, 0.49; 95% CI, 0.32-0.75; P = .001).

An excellent outcome on the modified Rankin Scale (mRS) disability score (mRS, 0-1) at 90 days was seen in 75% of tirofiban vs 68% of aspirin patients, a nonsignificant difference.

A good outcome (mRS, 0-2) occurred in 89% of tirofiban vs 86% of aspirin patients, again a nonsignificant difference.

There were no symptomatic intracerebral hemorrhages within 72 hours after randomization (the primary safety endpoint) in either group, and the incidence of systemic bleeding also did not differ significantly between the groups.

Dr. Wenbo concluded that further randomized clinical trials are needed to determine the efficacy of tirofiban on functional outcomes.

‘Promising Results’

Commenting on the study for this news organization, conference chair, Tudor Jovin, MD, Cooper Medical School of Rowan University, Camden, New Jersey, and vice-chair, Lauren Sansing, MD, Yale School of Medicine, New Haven, Connecticut, both said they thought the results were promising.

“This study didn’t show any long-term outcome benefit, but this was a smaller study, and the results need to be replicated in a larger study with sufficient power to look at longer-term outcomes,” Sansing noted. “But we don’t have anything better than aspirin at present for these patients, so it’s exciting that there may be something in the pipeline for this group.”

Dr. Jovin pointed out that the TREND trial selected patients on the cause of their stroke, in line with the practice of precision medicine.

“By excluding patients who received thrombolysis or thrombectomy and those who had cardioembolic strokes, we are left with a population who we don’t have many treatment options for,” he said. “These are patients with smaller or moderate strokes who may arrive too late for thrombolysis. It would be great to be able to do something more than just aspirin for these patients.”

Dr. Jovin noted that the study was underpowered to show long-term benefits, but there were some promising trends.

“It stands to reason that if neurologic function does not get worse in the early hours and days after stroke, then the long-term outcomes are likely to be better,” he noted. “But this needs to be confirmed in larger trials.”

Interestingly, another study, the MOST trial, also presented at the ISC-24 meeting, showed no benefit with the IV antithrombotic agents argatroban or eptifibatide on 90-day functional outcomes when added to thrombolysis in acute ischemic stroke.

Dr. Jovin pointed out that the MOST and TREND trials included different populations of patients — the MOST patients received thrombolysis, while the TREND patients did not. And in the MOST trial, about half the patients had a large vessel occlusion and underwent thrombectomy, whereas these patients were excluded in TREND.

Dr. Sansing added that patients in the TREND trial may have had small vessel disease or other atherosclerotic disease, or strokes due to the narrowing of vessels or due to an unknown cause. They were also given 3 days of IV tirofiban, whereas the duration of antithrombotic treatment in MOST was shorter.

The TREND study was funded by the National Key Research and Development Program of China, the National Science Foundation of Beijing Municipality, and the Beijing Municipal Science and Technology Commission.

A version of this article appeared on Medscape.com.

Intravenous (IV) administration of the antiplatelet agent tirofiban for 72 hours was associated with a reduction in early neurologic deterioration compared with oral aspirin therapy in patients with acute ischemic stroke, in the randomized TREND trial.

The results were presented at the International Stroke Conference 2024, held on February 7-9 in Phoenix, Arizona.

Lead author Zhao Wenbo, MD, Xuanwu Hospital, Beijing, China, noted that neurologic deterioration, characterized by a sudden onset and quick peak of neurologic deficits, is a common phenomenon in acute ischemic stroke and is strongly associated with poor clinical outcomes.

Ischemic stroke progression is the main cause of neurologic deterioration, especially during the first few days after onset, Dr. Wenbo said. Several clinical studies have found that intensive antiplatelet therapy may prevent early neurologic deterioration and improve functional outcomes, but administering oral antiplatelet agents can be difficult because of dysphagia, he reported.

The TREND trial was conducted to investigate whether IV tirofiban could prevent early neurologic deterioration without increasing the risk for symptomatic intracerebral hemorrhage in acute ischemic stroke.

The study included 426 patients with acute ischemic stroke within 24 hours of symptom onset who had a neurologic deficit attributed to focal cerebral ischemia and a National Institutes of Health Stroke Scale (NIHSS) score between 4 and 20 points and who were not treated with thrombolysis or endovascular thrombectomy. Patients with cardioembolic stroke were also excluded.

Patients were a median of 10-12 hours from symptom onset and had a baseline NIHSS score of 5.

They were randomized to IV tirofiban or oral aspirin for 72 hours. All patients were then continued on oral antiplatelet therapy.

The primary efficacy outcome was neurologic deterioration within 72 hours after randomization, defined as an increase in NIHSS score of 4 points or more.

This occurred in nine patients (4.2%) in the tirofiban group vs 28 (13.2%) in the control group (relative risk, 0.32; 95% CI, 0.15-0.66; P = .002).

A consistent benefit of IV tirofiban was seen across all subgroups.

The secondary endpoint of neurologic deterioration within 72 hours after randomization, defined as an increase of NIHSS score of 2 points or more, was also significantly reduced. This occurred in 11.7% of the tirofiban group vs 23.6% of the aspirin group (RR, 0.49; 95% CI, 0.32-0.75; P = .001).

An excellent outcome on the modified Rankin Scale (mRS) disability score (mRS, 0-1) at 90 days was seen in 75% of tirofiban vs 68% of aspirin patients, a nonsignificant difference.

A good outcome (mRS, 0-2) occurred in 89% of tirofiban vs 86% of aspirin patients, again a nonsignificant difference.

There were no symptomatic intracerebral hemorrhages within 72 hours after randomization (the primary safety endpoint) in either group, and the incidence of systemic bleeding also did not differ significantly between the groups.

Dr. Wenbo concluded that further randomized clinical trials are needed to determine the efficacy of tirofiban on functional outcomes.

‘Promising Results’

Commenting on the study for this news organization, conference chair, Tudor Jovin, MD, Cooper Medical School of Rowan University, Camden, New Jersey, and vice-chair, Lauren Sansing, MD, Yale School of Medicine, New Haven, Connecticut, both said they thought the results were promising.

“This study didn’t show any long-term outcome benefit, but this was a smaller study, and the results need to be replicated in a larger study with sufficient power to look at longer-term outcomes,” Sansing noted. “But we don’t have anything better than aspirin at present for these patients, so it’s exciting that there may be something in the pipeline for this group.”

Dr. Jovin pointed out that the TREND trial selected patients on the cause of their stroke, in line with the practice of precision medicine.

“By excluding patients who received thrombolysis or thrombectomy and those who had cardioembolic strokes, we are left with a population who we don’t have many treatment options for,” he said. “These are patients with smaller or moderate strokes who may arrive too late for thrombolysis. It would be great to be able to do something more than just aspirin for these patients.”

Dr. Jovin noted that the study was underpowered to show long-term benefits, but there were some promising trends.

“It stands to reason that if neurologic function does not get worse in the early hours and days after stroke, then the long-term outcomes are likely to be better,” he noted. “But this needs to be confirmed in larger trials.”

Interestingly, another study, the MOST trial, also presented at the ISC-24 meeting, showed no benefit with the IV antithrombotic agents argatroban or eptifibatide on 90-day functional outcomes when added to thrombolysis in acute ischemic stroke.

Dr. Jovin pointed out that the MOST and TREND trials included different populations of patients — the MOST patients received thrombolysis, while the TREND patients did not. And in the MOST trial, about half the patients had a large vessel occlusion and underwent thrombectomy, whereas these patients were excluded in TREND.

Dr. Sansing added that patients in the TREND trial may have had small vessel disease or other atherosclerotic disease, or strokes due to the narrowing of vessels or due to an unknown cause. They were also given 3 days of IV tirofiban, whereas the duration of antithrombotic treatment in MOST was shorter.

The TREND study was funded by the National Key Research and Development Program of China, the National Science Foundation of Beijing Municipality, and the Beijing Municipal Science and Technology Commission.

A version of this article appeared on Medscape.com.

Intravenous (IV) administration of the antiplatelet agent tirofiban for 72 hours was associated with a reduction in early neurologic deterioration compared with oral aspirin therapy in patients with acute ischemic stroke, in the randomized TREND trial.

The results were presented at the International Stroke Conference 2024, held on February 7-9 in Phoenix, Arizona.

Lead author Zhao Wenbo, MD, Xuanwu Hospital, Beijing, China, noted that neurologic deterioration, characterized by a sudden onset and quick peak of neurologic deficits, is a common phenomenon in acute ischemic stroke and is strongly associated with poor clinical outcomes.

Ischemic stroke progression is the main cause of neurologic deterioration, especially during the first few days after onset, Dr. Wenbo said. Several clinical studies have found that intensive antiplatelet therapy may prevent early neurologic deterioration and improve functional outcomes, but administering oral antiplatelet agents can be difficult because of dysphagia, he reported.

The TREND trial was conducted to investigate whether IV tirofiban could prevent early neurologic deterioration without increasing the risk for symptomatic intracerebral hemorrhage in acute ischemic stroke.

The study included 426 patients with acute ischemic stroke within 24 hours of symptom onset who had a neurologic deficit attributed to focal cerebral ischemia and a National Institutes of Health Stroke Scale (NIHSS) score between 4 and 20 points and who were not treated with thrombolysis or endovascular thrombectomy. Patients with cardioembolic stroke were also excluded.

Patients were a median of 10-12 hours from symptom onset and had a baseline NIHSS score of 5.

They were randomized to IV tirofiban or oral aspirin for 72 hours. All patients were then continued on oral antiplatelet therapy.

The primary efficacy outcome was neurologic deterioration within 72 hours after randomization, defined as an increase in NIHSS score of 4 points or more.

This occurred in nine patients (4.2%) in the tirofiban group vs 28 (13.2%) in the control group (relative risk, 0.32; 95% CI, 0.15-0.66; P = .002).

A consistent benefit of IV tirofiban was seen across all subgroups.

The secondary endpoint of neurologic deterioration within 72 hours after randomization, defined as an increase of NIHSS score of 2 points or more, was also significantly reduced. This occurred in 11.7% of the tirofiban group vs 23.6% of the aspirin group (RR, 0.49; 95% CI, 0.32-0.75; P = .001).

An excellent outcome on the modified Rankin Scale (mRS) disability score (mRS, 0-1) at 90 days was seen in 75% of tirofiban vs 68% of aspirin patients, a nonsignificant difference.

A good outcome (mRS, 0-2) occurred in 89% of tirofiban vs 86% of aspirin patients, again a nonsignificant difference.

There were no symptomatic intracerebral hemorrhages within 72 hours after randomization (the primary safety endpoint) in either group, and the incidence of systemic bleeding also did not differ significantly between the groups.

Dr. Wenbo concluded that further randomized clinical trials are needed to determine the efficacy of tirofiban on functional outcomes.

‘Promising Results’

Commenting on the study for this news organization, conference chair, Tudor Jovin, MD, Cooper Medical School of Rowan University, Camden, New Jersey, and vice-chair, Lauren Sansing, MD, Yale School of Medicine, New Haven, Connecticut, both said they thought the results were promising.

“This study didn’t show any long-term outcome benefit, but this was a smaller study, and the results need to be replicated in a larger study with sufficient power to look at longer-term outcomes,” Sansing noted. “But we don’t have anything better than aspirin at present for these patients, so it’s exciting that there may be something in the pipeline for this group.”

Dr. Jovin pointed out that the TREND trial selected patients on the cause of their stroke, in line with the practice of precision medicine.

“By excluding patients who received thrombolysis or thrombectomy and those who had cardioembolic strokes, we are left with a population who we don’t have many treatment options for,” he said. “These are patients with smaller or moderate strokes who may arrive too late for thrombolysis. It would be great to be able to do something more than just aspirin for these patients.”

Dr. Jovin noted that the study was underpowered to show long-term benefits, but there were some promising trends.

“It stands to reason that if neurologic function does not get worse in the early hours and days after stroke, then the long-term outcomes are likely to be better,” he noted. “But this needs to be confirmed in larger trials.”

Interestingly, another study, the MOST trial, also presented at the ISC-24 meeting, showed no benefit with the IV antithrombotic agents argatroban or eptifibatide on 90-day functional outcomes when added to thrombolysis in acute ischemic stroke.

Dr. Jovin pointed out that the MOST and TREND trials included different populations of patients — the MOST patients received thrombolysis, while the TREND patients did not. And in the MOST trial, about half the patients had a large vessel occlusion and underwent thrombectomy, whereas these patients were excluded in TREND.

Dr. Sansing added that patients in the TREND trial may have had small vessel disease or other atherosclerotic disease, or strokes due to the narrowing of vessels or due to an unknown cause. They were also given 3 days of IV tirofiban, whereas the duration of antithrombotic treatment in MOST was shorter.

The TREND study was funded by the National Key Research and Development Program of China, the National Science Foundation of Beijing Municipality, and the Beijing Municipal Science and Technology Commission.

A version of this article appeared on Medscape.com.

Exposure to even moderate concentrations of radon is associated with a significant increase in stroke risk, new research suggests.

An analysis of radon exposures in more than 150,000 postmenopausal women in the Women’s Health Initiative revealed a 14% higher stroke risk in those exposed to the highest concentrations compared with those exposed to the lowest concentrations. Even moderate concentrations of radon were associated with a 6% higher stroke risk.

Radon is the second leading cause of lung cancer, but little was known about how exposure to the gas might affect stroke risk in women. 

“Our research found an increased risk of stroke among participants exposed to radon above — and as many as 2 picocuries per liter (pCi/L) below — concentrations that usually trigger Environmental Protection Agency recommendations to install a home radon mitigation system,” senior author Eric A. Whitsel, MD, MPH, professor of epidemiology and medicine, University of North Carolina, Chapel Hill, said in a news release.

The study was published online on January 31, 2024, in Neurology.

Women Particularly Affected

Radon is a naturally occurring odorless radioactive gas produced when uranium or radium break down in rocks and soil. Its presence is increasing as a result of climate change, and it is increasingly being found in people’s homes. When inhaled, this air pollutant releases ionizing radiation in the lungs and is seen as second only to smoking as an established cause of lung cancer.

The National Radon Action Plan of the US Environmental Protection Agency (EPA) lays out testing and mitigation guidelines based on the known role of radon in lung carcinogenesis. But radon testing and mitigation are less common than recommended, and the EPA’s action plan doesn’t cover diseases other than lung cancer.

Compared with men, women have a higher rate of stroke and, in the US, typically spend about 11% more hours per day indoors at home, which investigators note highlights a “potential role of the residential environment among other risk factors specific to women.”

Researchers examined longitudinal associations between home radon exposure and incident stroke in 158,910 women at baseline (mean age 63.2 years; 83% White) over a mean follow-up of 13.4 years. During this time, participants experienced a total of 6979 strokes.

Participants’ home addresses were linked to radon concentration data drawn from the US Geological Survey and the EPA, which recommends that average indoor radon concentrations not exceed 4 pCi/L. 

The highest radon exposure group resided in areas where average radon concentrations were < 4 pCi/L; the middle exposure group lived in regions with average concentrations of 2-4 pCi/L; and the lowest exposure group lived in areas with average concentrations < 2 pCi/L. 

The researchers adjusted for demographic, social, behavioral, and clinical characteristics.

Public Health Implications

The incidence rates of stroke per 100,000 women in the lowest, middle, and highest radon concentration areas were 333, 343, and 349, respectively.

Stroke risk was 6% higher among those in the middle exposure group (adjusted hazard ratio [aHR], 1.06; 95% CI, 0.99-1.13) and 14% higher in the highest exposure group (aHR, 1.14; 95% CI, 1.05-1.22) compared with the lowest exposure group.

Notably, stroke risk was significant even at concentrations ranging from 2 to 4 pCi/L (P = .0004) vs < 2 pCi/L, which is below the EPA›s Radon Action Level for mitigation. 

The findings remained robust in sensitivity analyses, although the associations were slightly stronger for ischemic stroke (especially cardioembolic, small-vessel occlusive, and very large artery atherosclerotic) compared with hemorrhagic stroke.

“Radon is an indoor air pollutant that can only be detected through testing that measures concentrations of the gas in homes,” Dr. Whitsel said in the release. “More studies are needed to confirm our findings. Confirmation would present an opportunity to improve public health by addressing an emerging risk factor for stroke.”

The study lacked gender and racial/ethnic diversity, so the findings may not be generalizable to other populations. 

“Replication studies of individual-level radon exposures are needed to confirm this positive radon-stroke association,” the authors write. “Confirmation would present a potential opportunity to affect public health by addressing a pervasive environmental risk factor for stroke and thereby merit reconsideration of extant radon policy.”

The study was funded by the National Institute of Environmental Health Sciences and National Heart, Lung, and Blood Institute. Dr. Whitsel and coauthors report no relevant financial relationships.

A version of this article appeared on Medscape.com.

Exposure to even moderate concentrations of radon is associated with a significant increase in stroke risk, new research suggests.

An analysis of radon exposures in more than 150,000 postmenopausal women in the Women’s Health Initiative revealed a 14% higher stroke risk in those exposed to the highest concentrations compared with those exposed to the lowest concentrations. Even moderate concentrations of radon were associated with a 6% higher stroke risk.

Radon is the second leading cause of lung cancer, but little was known about how exposure to the gas might affect stroke risk in women. 

“Our research found an increased risk of stroke among participants exposed to radon above — and as many as 2 picocuries per liter (pCi/L) below — concentrations that usually trigger Environmental Protection Agency recommendations to install a home radon mitigation system,” senior author Eric A. Whitsel, MD, MPH, professor of epidemiology and medicine, University of North Carolina, Chapel Hill, said in a news release.

The study was published online on January 31, 2024, in Neurology.

Women Particularly Affected

Radon is a naturally occurring odorless radioactive gas produced when uranium or radium break down in rocks and soil. Its presence is increasing as a result of climate change, and it is increasingly being found in people’s homes. When inhaled, this air pollutant releases ionizing radiation in the lungs and is seen as second only to smoking as an established cause of lung cancer.

The National Radon Action Plan of the US Environmental Protection Agency (EPA) lays out testing and mitigation guidelines based on the known role of radon in lung carcinogenesis. But radon testing and mitigation are less common than recommended, and the EPA’s action plan doesn’t cover diseases other than lung cancer.

Compared with men, women have a higher rate of stroke and, in the US, typically spend about 11% more hours per day indoors at home, which investigators note highlights a “potential role of the residential environment among other risk factors specific to women.”

Researchers examined longitudinal associations between home radon exposure and incident stroke in 158,910 women at baseline (mean age 63.2 years; 83% White) over a mean follow-up of 13.4 years. During this time, participants experienced a total of 6979 strokes.

Participants’ home addresses were linked to radon concentration data drawn from the US Geological Survey and the EPA, which recommends that average indoor radon concentrations not exceed 4 pCi/L. 

The highest radon exposure group resided in areas where average radon concentrations were < 4 pCi/L; the middle exposure group lived in regions with average concentrations of 2-4 pCi/L; and the lowest exposure group lived in areas with average concentrations < 2 pCi/L. 

The researchers adjusted for demographic, social, behavioral, and clinical characteristics.

Public Health Implications

The incidence rates of stroke per 100,000 women in the lowest, middle, and highest radon concentration areas were 333, 343, and 349, respectively.

Stroke risk was 6% higher among those in the middle exposure group (adjusted hazard ratio [aHR], 1.06; 95% CI, 0.99-1.13) and 14% higher in the highest exposure group (aHR, 1.14; 95% CI, 1.05-1.22) compared with the lowest exposure group.

Notably, stroke risk was significant even at concentrations ranging from 2 to 4 pCi/L (P = .0004) vs < 2 pCi/L, which is below the EPA›s Radon Action Level for mitigation. 

The findings remained robust in sensitivity analyses, although the associations were slightly stronger for ischemic stroke (especially cardioembolic, small-vessel occlusive, and very large artery atherosclerotic) compared with hemorrhagic stroke.

“Radon is an indoor air pollutant that can only be detected through testing that measures concentrations of the gas in homes,” Dr. Whitsel said in the release. “More studies are needed to confirm our findings. Confirmation would present an opportunity to improve public health by addressing an emerging risk factor for stroke.”

The study lacked gender and racial/ethnic diversity, so the findings may not be generalizable to other populations. 

“Replication studies of individual-level radon exposures are needed to confirm this positive radon-stroke association,” the authors write. “Confirmation would present a potential opportunity to affect public health by addressing a pervasive environmental risk factor for stroke and thereby merit reconsideration of extant radon policy.”

The study was funded by the National Institute of Environmental Health Sciences and National Heart, Lung, and Blood Institute. Dr. Whitsel and coauthors report no relevant financial relationships.

A version of this article appeared on Medscape.com.

Exposure to even moderate concentrations of radon is associated with a significant increase in stroke risk, new research suggests.

An analysis of radon exposures in more than 150,000 postmenopausal women in the Women’s Health Initiative revealed a 14% higher stroke risk in those exposed to the highest concentrations compared with those exposed to the lowest concentrations. Even moderate concentrations of radon were associated with a 6% higher stroke risk.

Radon is the second leading cause of lung cancer, but little was known about how exposure to the gas might affect stroke risk in women. 

“Our research found an increased risk of stroke among participants exposed to radon above — and as many as 2 picocuries per liter (pCi/L) below — concentrations that usually trigger Environmental Protection Agency recommendations to install a home radon mitigation system,” senior author Eric A. Whitsel, MD, MPH, professor of epidemiology and medicine, University of North Carolina, Chapel Hill, said in a news release.

The study was published online on January 31, 2024, in Neurology.

Women Particularly Affected

Radon is a naturally occurring odorless radioactive gas produced when uranium or radium break down in rocks and soil. Its presence is increasing as a result of climate change, and it is increasingly being found in people’s homes. When inhaled, this air pollutant releases ionizing radiation in the lungs and is seen as second only to smoking as an established cause of lung cancer.

The National Radon Action Plan of the US Environmental Protection Agency (EPA) lays out testing and mitigation guidelines based on the known role of radon in lung carcinogenesis. But radon testing and mitigation are less common than recommended, and the EPA’s action plan doesn’t cover diseases other than lung cancer.

Compared with men, women have a higher rate of stroke and, in the US, typically spend about 11% more hours per day indoors at home, which investigators note highlights a “potential role of the residential environment among other risk factors specific to women.”

Researchers examined longitudinal associations between home radon exposure and incident stroke in 158,910 women at baseline (mean age 63.2 years; 83% White) over a mean follow-up of 13.4 years. During this time, participants experienced a total of 6979 strokes.

Participants’ home addresses were linked to radon concentration data drawn from the US Geological Survey and the EPA, which recommends that average indoor radon concentrations not exceed 4 pCi/L. 

The highest radon exposure group resided in areas where average radon concentrations were < 4 pCi/L; the middle exposure group lived in regions with average concentrations of 2-4 pCi/L; and the lowest exposure group lived in areas with average concentrations < 2 pCi/L. 

The researchers adjusted for demographic, social, behavioral, and clinical characteristics.

Public Health Implications

The incidence rates of stroke per 100,000 women in the lowest, middle, and highest radon concentration areas were 333, 343, and 349, respectively.

Stroke risk was 6% higher among those in the middle exposure group (adjusted hazard ratio [aHR], 1.06; 95% CI, 0.99-1.13) and 14% higher in the highest exposure group (aHR, 1.14; 95% CI, 1.05-1.22) compared with the lowest exposure group.

Notably, stroke risk was significant even at concentrations ranging from 2 to 4 pCi/L (P = .0004) vs < 2 pCi/L, which is below the EPA›s Radon Action Level for mitigation. 

The findings remained robust in sensitivity analyses, although the associations were slightly stronger for ischemic stroke (especially cardioembolic, small-vessel occlusive, and very large artery atherosclerotic) compared with hemorrhagic stroke.

“Radon is an indoor air pollutant that can only be detected through testing that measures concentrations of the gas in homes,” Dr. Whitsel said in the release. “More studies are needed to confirm our findings. Confirmation would present an opportunity to improve public health by addressing an emerging risk factor for stroke.”

The study lacked gender and racial/ethnic diversity, so the findings may not be generalizable to other populations. 

“Replication studies of individual-level radon exposures are needed to confirm this positive radon-stroke association,” the authors write. “Confirmation would present a potential opportunity to affect public health by addressing a pervasive environmental risk factor for stroke and thereby merit reconsideration of extant radon policy.”

The study was funded by the National Institute of Environmental Health Sciences and National Heart, Lung, and Blood Institute. Dr. Whitsel and coauthors report no relevant financial relationships.

A version of this article appeared on Medscape.com.

Black women who develop high blood pressure before age 35 have a threefold increased risk of having a midlife stroke, new observational data suggested.

The Black Women’s Health Study, which has followed 59,000 participants in the United States since the 1990s, also showed that those who develop hypertension before age 45 have twice the risk of suffering a stroke.

“The really concerning thing about this data is the high proportion of young Black women who had high blood pressure and are suffering strokes relatively early in life,” the study’s lead author, Hugo J. Aparicio, MD, associate professor of neurology at Boston University Chobanian & Avedisian School of Medicine, told this news organization. “This can lead to a burden of disability in relatively young women who may be at the prime of their life, pursuing careers and looking after family.”

Dr. Aparicio will present the data in full at the International Stroke Conference 2024 to be held in Phoenix, Arizona, Feb. 7-9.

He explained that while there has been good progress in reducing stroke rates in older people over the past decades, there is a concerning observation from multiple datasets showing that stroke rates in midlife have been plateauing or even increasing in recent years.

“For Black women specifically, there is a concern, as we know this group has higher rates of raised blood pressure and stroke overall,” said Dr. Aparicio. “We were interested in looking at whether the onset of hypertension at an earlier age in this group is one of the reasons for the increased stroke risk in midlife.”

The researchers analyzed data from the Black Women’s Health Study, a prospective study of 59,000 Black women from across the United States. The baseline year for this analysis, which included 46,754 stroke-free participants younger than age 65 (mean age, 42 years), was the 1999 questionnaire.

History of hypertension, defined as physician-diagnosed hypertension with the use of an antihypertensive medication, and of stroke occurrence was determined by self-report. It has been shown in previous studies that these self-reported data on incidence of hypertension in this dataset are highly reliable, Dr. Aparicio noted.

At baseline, 10.5% of participants aged 45-64 years had hypertension. Stroke occurred in 3.2% of individuals over a mean follow-up of 17 years.

Black women with hypertension before age 45 had a higher risk for midlife stroke (hazard ratio [HR], 2.23; 95% CI, 1.79-2.78), after adjustment for age, neighborhood socioeconomic status, residence in Stroke Belt, smoking, body mass index, and diabetes than women with no history of hypertension.

The risk was also increased with hypertension at midlife ages 45-64 years (HR, 1.69; 95% CI, 1.47-1.95) and was highest among those with hypertension at ages 24-34 years (HR, 3.15; 95% CI, 1.92-5.16).

“Our results show that among young Black women, those with hypertension have a much higher stroke risk than those without hypertension, even if they are taking antihypertensive medication,” Dr. Aparicio said. “This underscores how potent hypertension is as a risk factor for stroke.”

He concluded that both individuals and doctors need to realize that hypertension and stroke are not problems of the elderly exclusively.

“These are conditions that need to be addressed very early in life. This is even more important for Black women, as they are a high-risk group. They need to pay attention to blood pressure numbers early in life — ideally from adolescence — to catch levels before they become too elevated,” Dr. Aparicio said.

“We also need to address lifestyle changes including diet, physical activity, sleep habits, and address other cardiovascular risk factors such as cholesterol and body mass index, so we can prevent strokes from occurring,” he added. “At the policy level, we need to advocate, provide and fund primary prevention measures, and enable earlier screening and better treatment.”

The Role of Psychosocial Stressors

Commenting on the study, the American Heart Association immediate past president, Michelle A. Albert, MD, professor of medicine at the University of California, San Francisco, emphasized the importance of regular primary care appointments to screen for high blood pressure and other cardiovascular risk factors.

She pointed out that one of the contributing factors that may increase the risk for Black women is their disproportionate experience of psychosocial stressors and chronic cumulative stress.

This could include stress related to financial issues, racism and other forms of bias, the neighborhood environment, and having to take care of multiple generations of family with limited resources.

“These are some of the things that are less talked about as going into the heightened risk for many cardiovascular risk factors, including hypertension, very early in life for Black women that we need to bring to the forefront of conversations,” Dr. Albert said.

“These stressors not only impact hypertension onset but also they impact one’s ability to be able to seek help, and once the help is sought, to be able to sustain the therapies recommended and the interventions recommended,” she added.

The authors reported no relevant disclosures.
 

A version of this article appeared on Medscape.com.

Black women who develop high blood pressure before age 35 have a threefold increased risk of having a midlife stroke, new observational data suggested.

The Black Women’s Health Study, which has followed 59,000 participants in the United States since the 1990s, also showed that those who develop hypertension before age 45 have twice the risk of suffering a stroke.

“The really concerning thing about this data is the high proportion of young Black women who had high blood pressure and are suffering strokes relatively early in life,” the study’s lead author, Hugo J. Aparicio, MD, associate professor of neurology at Boston University Chobanian & Avedisian School of Medicine, told this news organization. “This can lead to a burden of disability in relatively young women who may be at the prime of their life, pursuing careers and looking after family.”

Dr. Aparicio will present the data in full at the International Stroke Conference 2024 to be held in Phoenix, Arizona, Feb. 7-9.

He explained that while there has been good progress in reducing stroke rates in older people over the past decades, there is a concerning observation from multiple datasets showing that stroke rates in midlife have been plateauing or even increasing in recent years.

“For Black women specifically, there is a concern, as we know this group has higher rates of raised blood pressure and stroke overall,” said Dr. Aparicio. “We were interested in looking at whether the onset of hypertension at an earlier age in this group is one of the reasons for the increased stroke risk in midlife.”

The researchers analyzed data from the Black Women’s Health Study, a prospective study of 59,000 Black women from across the United States. The baseline year for this analysis, which included 46,754 stroke-free participants younger than age 65 (mean age, 42 years), was the 1999 questionnaire.

History of hypertension, defined as physician-diagnosed hypertension with the use of an antihypertensive medication, and of stroke occurrence was determined by self-report. It has been shown in previous studies that these self-reported data on incidence of hypertension in this dataset are highly reliable, Dr. Aparicio noted.

At baseline, 10.5% of participants aged 45-64 years had hypertension. Stroke occurred in 3.2% of individuals over a mean follow-up of 17 years.

Black women with hypertension before age 45 had a higher risk for midlife stroke (hazard ratio [HR], 2.23; 95% CI, 1.79-2.78), after adjustment for age, neighborhood socioeconomic status, residence in Stroke Belt, smoking, body mass index, and diabetes than women with no history of hypertension.

The risk was also increased with hypertension at midlife ages 45-64 years (HR, 1.69; 95% CI, 1.47-1.95) and was highest among those with hypertension at ages 24-34 years (HR, 3.15; 95% CI, 1.92-5.16).

“Our results show that among young Black women, those with hypertension have a much higher stroke risk than those without hypertension, even if they are taking antihypertensive medication,” Dr. Aparicio said. “This underscores how potent hypertension is as a risk factor for stroke.”

He concluded that both individuals and doctors need to realize that hypertension and stroke are not problems of the elderly exclusively.

“These are conditions that need to be addressed very early in life. This is even more important for Black women, as they are a high-risk group. They need to pay attention to blood pressure numbers early in life — ideally from adolescence — to catch levels before they become too elevated,” Dr. Aparicio said.

“We also need to address lifestyle changes including diet, physical activity, sleep habits, and address other cardiovascular risk factors such as cholesterol and body mass index, so we can prevent strokes from occurring,” he added. “At the policy level, we need to advocate, provide and fund primary prevention measures, and enable earlier screening and better treatment.”

The Role of Psychosocial Stressors

Commenting on the study, the American Heart Association immediate past president, Michelle A. Albert, MD, professor of medicine at the University of California, San Francisco, emphasized the importance of regular primary care appointments to screen for high blood pressure and other cardiovascular risk factors.

She pointed out that one of the contributing factors that may increase the risk for Black women is their disproportionate experience of psychosocial stressors and chronic cumulative stress.

This could include stress related to financial issues, racism and other forms of bias, the neighborhood environment, and having to take care of multiple generations of family with limited resources.

“These are some of the things that are less talked about as going into the heightened risk for many cardiovascular risk factors, including hypertension, very early in life for Black women that we need to bring to the forefront of conversations,” Dr. Albert said.

“These stressors not only impact hypertension onset but also they impact one’s ability to be able to seek help, and once the help is sought, to be able to sustain the therapies recommended and the interventions recommended,” she added.

The authors reported no relevant disclosures.
 

A version of this article appeared on Medscape.com.

Black women who develop high blood pressure before age 35 have a threefold increased risk of having a midlife stroke, new observational data suggested.

The Black Women’s Health Study, which has followed 59,000 participants in the United States since the 1990s, also showed that those who develop hypertension before age 45 have twice the risk of suffering a stroke.

“The really concerning thing about this data is the high proportion of young Black women who had high blood pressure and are suffering strokes relatively early in life,” the study’s lead author, Hugo J. Aparicio, MD, associate professor of neurology at Boston University Chobanian & Avedisian School of Medicine, told this news organization. “This can lead to a burden of disability in relatively young women who may be at the prime of their life, pursuing careers and looking after family.”

Dr. Aparicio will present the data in full at the International Stroke Conference 2024 to be held in Phoenix, Arizona, Feb. 7-9.

He explained that while there has been good progress in reducing stroke rates in older people over the past decades, there is a concerning observation from multiple datasets showing that stroke rates in midlife have been plateauing or even increasing in recent years.

“For Black women specifically, there is a concern, as we know this group has higher rates of raised blood pressure and stroke overall,” said Dr. Aparicio. “We were interested in looking at whether the onset of hypertension at an earlier age in this group is one of the reasons for the increased stroke risk in midlife.”

The researchers analyzed data from the Black Women’s Health Study, a prospective study of 59,000 Black women from across the United States. The baseline year for this analysis, which included 46,754 stroke-free participants younger than age 65 (mean age, 42 years), was the 1999 questionnaire.

History of hypertension, defined as physician-diagnosed hypertension with the use of an antihypertensive medication, and of stroke occurrence was determined by self-report. It has been shown in previous studies that these self-reported data on incidence of hypertension in this dataset are highly reliable, Dr. Aparicio noted.

At baseline, 10.5% of participants aged 45-64 years had hypertension. Stroke occurred in 3.2% of individuals over a mean follow-up of 17 years.

Black women with hypertension before age 45 had a higher risk for midlife stroke (hazard ratio [HR], 2.23; 95% CI, 1.79-2.78), after adjustment for age, neighborhood socioeconomic status, residence in Stroke Belt, smoking, body mass index, and diabetes than women with no history of hypertension.

The risk was also increased with hypertension at midlife ages 45-64 years (HR, 1.69; 95% CI, 1.47-1.95) and was highest among those with hypertension at ages 24-34 years (HR, 3.15; 95% CI, 1.92-5.16).

“Our results show that among young Black women, those with hypertension have a much higher stroke risk than those without hypertension, even if they are taking antihypertensive medication,” Dr. Aparicio said. “This underscores how potent hypertension is as a risk factor for stroke.”

He concluded that both individuals and doctors need to realize that hypertension and stroke are not problems of the elderly exclusively.

“These are conditions that need to be addressed very early in life. This is even more important for Black women, as they are a high-risk group. They need to pay attention to blood pressure numbers early in life — ideally from adolescence — to catch levels before they become too elevated,” Dr. Aparicio said.

“We also need to address lifestyle changes including diet, physical activity, sleep habits, and address other cardiovascular risk factors such as cholesterol and body mass index, so we can prevent strokes from occurring,” he added. “At the policy level, we need to advocate, provide and fund primary prevention measures, and enable earlier screening and better treatment.”

The Role of Psychosocial Stressors

Commenting on the study, the American Heart Association immediate past president, Michelle A. Albert, MD, professor of medicine at the University of California, San Francisco, emphasized the importance of regular primary care appointments to screen for high blood pressure and other cardiovascular risk factors.

She pointed out that one of the contributing factors that may increase the risk for Black women is their disproportionate experience of psychosocial stressors and chronic cumulative stress.

This could include stress related to financial issues, racism and other forms of bias, the neighborhood environment, and having to take care of multiple generations of family with limited resources.

“These are some of the things that are less talked about as going into the heightened risk for many cardiovascular risk factors, including hypertension, very early in life for Black women that we need to bring to the forefront of conversations,” Dr. Albert said.

“These stressors not only impact hypertension onset but also they impact one’s ability to be able to seek help, and once the help is sought, to be able to sustain the therapies recommended and the interventions recommended,” she added.

The authors reported no relevant disclosures.
 

A version of this article appeared on Medscape.com.

TOPLINE:

A daily low dose of colchicine significantly reduces ischemic cardiovascular events in patients with type 2 diabetes (T2D) and a recent myocardial infarction (MI). 

METHODOLOGY:

• After an MI, patients with vs without T2D have a higher risk for another cardiovascular event.
• The Colchicine Cardiovascular Outcomes Trial (COLCOT), a randomized, double-blinded trial, found a lower risk for ischemic cardiovascular events with 0.5 mg colchicine taken daily vs placebo, initiated within 30 days of an MI.
• Researchers conducted a prespecified subgroup analysis of 959 adult patients with T2D (mean age, 62.4 years; 22.2% women) in COLCOT (462 patients in colchicine and 497 patients in placebo groups).
• The primary efficacy endpoint was a composite of cardiovascular death, resuscitated cardiac arrest, MI, stroke, or urgent hospitalization for angina requiring coronary revascularization within a median 23 months.
• The patients were taking a variety of appropriate medications, including aspirin and another antiplatelet agent and a statin (98%-99%) and metformin (75%-76%).

TAKEAWAY:

• The risk for the primary endpoint was reduced by 35% in patients with T2D who received colchicine than in those who received placebo (hazard ratio, 0.65; P = .03).
• The primary endpoint event rate per 100 patient-months was significantly lower in the colchicine group than in the placebo group (rate ratio, 0.53; P = .01).
• The frequencies of adverse events were similar in both the treatment and placebo groups (14.6% and 12.8%, respectively; P = .41), with gastrointestinal adverse events being the most common.
• In COLCOT, patients with T2D had a 1.86-fold higher risk for a primary endpoint cardiovascular event, but there was no significant difference in the primary endpoint between those with and without T2D on colchicine.

IN PRACTICE:

“Patients with both T2D and a recent MI derive a large benefit from inflammation-reducing therapy with colchicine,” the authors noted.

SOURCE:

This study, led by François Roubille, University Hospital of Montpellier, France, was published online on January 5, 2024, in Diabetes Care. 

LIMITATIONS:

Patients were not stratified at inclusion for the presence of diabetes. Also, the study did not evaluate the role of glycated hemoglobin and low-density lipoprotein cholesterol, as well as the effects of different glucose-lowering medications or possible hypoglycemic episodes.

DISCLOSURES:

The COLCOT study was funded by the Government of Quebec, the Canadian Institutes of Health Research, and philanthropic foundations. Coauthors Jean-Claude Tardif and Wolfgang Koenig declared receiving research grants, honoraria, advisory board fees, and lecture fees from pharmaceutical companies, as well as having other ties with various sources.
 

A version of this article appeared on Medscape.com.

TOPLINE:

A daily low dose of colchicine significantly reduces ischemic cardiovascular events in patients with type 2 diabetes (T2D) and a recent myocardial infarction (MI). 

METHODOLOGY:

• After an MI, patients with vs without T2D have a higher risk for another cardiovascular event.
• The Colchicine Cardiovascular Outcomes Trial (COLCOT), a randomized, double-blinded trial, found a lower risk for ischemic cardiovascular events with 0.5 mg colchicine taken daily vs placebo, initiated within 30 days of an MI.
• Researchers conducted a prespecified subgroup analysis of 959 adult patients with T2D (mean age, 62.4 years; 22.2% women) in COLCOT (462 patients in colchicine and 497 patients in placebo groups).
• The primary efficacy endpoint was a composite of cardiovascular death, resuscitated cardiac arrest, MI, stroke, or urgent hospitalization for angina requiring coronary revascularization within a median 23 months.
• The patients were taking a variety of appropriate medications, including aspirin and another antiplatelet agent and a statin (98%-99%) and metformin (75%-76%).

TAKEAWAY:

• The risk for the primary endpoint was reduced by 35% in patients with T2D who received colchicine than in those who received placebo (hazard ratio, 0.65; P = .03).
• The primary endpoint event rate per 100 patient-months was significantly lower in the colchicine group than in the placebo group (rate ratio, 0.53; P = .01).
• The frequencies of adverse events were similar in both the treatment and placebo groups (14.6% and 12.8%, respectively; P = .41), with gastrointestinal adverse events being the most common.
• In COLCOT, patients with T2D had a 1.86-fold higher risk for a primary endpoint cardiovascular event, but there was no significant difference in the primary endpoint between those with and without T2D on colchicine.

IN PRACTICE:

“Patients with both T2D and a recent MI derive a large benefit from inflammation-reducing therapy with colchicine,” the authors noted.

SOURCE:

This study, led by François Roubille, University Hospital of Montpellier, France, was published online on January 5, 2024, in Diabetes Care. 

LIMITATIONS:

Patients were not stratified at inclusion for the presence of diabetes. Also, the study did not evaluate the role of glycated hemoglobin and low-density lipoprotein cholesterol, as well as the effects of different glucose-lowering medications or possible hypoglycemic episodes.

DISCLOSURES:

The COLCOT study was funded by the Government of Quebec, the Canadian Institutes of Health Research, and philanthropic foundations. Coauthors Jean-Claude Tardif and Wolfgang Koenig declared receiving research grants, honoraria, advisory board fees, and lecture fees from pharmaceutical companies, as well as having other ties with various sources.
 

A version of this article appeared on Medscape.com.

TOPLINE:

A daily low dose of colchicine significantly reduces ischemic cardiovascular events in patients with type 2 diabetes (T2D) and a recent myocardial infarction (MI). 

METHODOLOGY:

• After an MI, patients with vs without T2D have a higher risk for another cardiovascular event.
• The Colchicine Cardiovascular Outcomes Trial (COLCOT), a randomized, double-blinded trial, found a lower risk for ischemic cardiovascular events with 0.5 mg colchicine taken daily vs placebo, initiated within 30 days of an MI.
• Researchers conducted a prespecified subgroup analysis of 959 adult patients with T2D (mean age, 62.4 years; 22.2% women) in COLCOT (462 patients in colchicine and 497 patients in placebo groups).
• The primary efficacy endpoint was a composite of cardiovascular death, resuscitated cardiac arrest, MI, stroke, or urgent hospitalization for angina requiring coronary revascularization within a median 23 months.
• The patients were taking a variety of appropriate medications, including aspirin and another antiplatelet agent and a statin (98%-99%) and metformin (75%-76%).

TAKEAWAY:

• The risk for the primary endpoint was reduced by 35% in patients with T2D who received colchicine than in those who received placebo (hazard ratio, 0.65; P = .03).
• The primary endpoint event rate per 100 patient-months was significantly lower in the colchicine group than in the placebo group (rate ratio, 0.53; P = .01).
• The frequencies of adverse events were similar in both the treatment and placebo groups (14.6% and 12.8%, respectively; P = .41), with gastrointestinal adverse events being the most common.
• In COLCOT, patients with T2D had a 1.86-fold higher risk for a primary endpoint cardiovascular event, but there was no significant difference in the primary endpoint between those with and without T2D on colchicine.

IN PRACTICE:

“Patients with both T2D and a recent MI derive a large benefit from inflammation-reducing therapy with colchicine,” the authors noted.

SOURCE:

This study, led by François Roubille, University Hospital of Montpellier, France, was published online on January 5, 2024, in Diabetes Care. 

LIMITATIONS:

Patients were not stratified at inclusion for the presence of diabetes. Also, the study did not evaluate the role of glycated hemoglobin and low-density lipoprotein cholesterol, as well as the effects of different glucose-lowering medications or possible hypoglycemic episodes.

DISCLOSURES:

The COLCOT study was funded by the Government of Quebec, the Canadian Institutes of Health Research, and philanthropic foundations. Coauthors Jean-Claude Tardif and Wolfgang Koenig declared receiving research grants, honoraria, advisory board fees, and lecture fees from pharmaceutical companies, as well as having other ties with various sources.
 

A version of this article appeared on Medscape.com.

TOPLINE: 

Among patients hospitalized with a first ischemic stroke, 80% were rehospitalized, primarily because of subsequent primary cardiovascular and cerebrovascular diagnoses.

METHODOLOGY:

• To gather information on post-stroke hospital admission, investigators followed 1412 participants (mean age, 72.4 years; 52.1% women, 35.3% Black individuals) from the Atherosclerosis Risk in Communities (ARIC) study who were living in Maryland, Minnesota, North Carolina, and Mississippi.
• Participants were recruited between 1987 and 1989 when they were 45-64 years old and were followed on an annual and then semiannual basis from the index discharge until discharge after their second hospitalization, death, or end of the study in December 2019.
• Specific diagnoses for each hospitalization were based on hospital records, discharge diagnoses, and annual and semiannual phone interviews.

TAKEAWAY: 

• During the study period, 1143 hospitalizations occurred over 41,849 person-months.
• 81% of participants were hospitalized over a maximum of 26.6 years of follow-up. Primary cardiovascular and cerebrovascular diagnoses were reported for half of readmissions.
• Over the follow-up period, compared with cardioembolic stroke, readmission risk was lower for thrombotic/lacunar stroke (adjusted hazard ratio [aHR], 0.82; 95% CI, 0.71-0.95) and hemorrhagic stroke (aHR, 0.74; 95% CI, 0.58-0.93). However, when adjusting for atrial fibrillation and competing risk for death, there were no significant differences between stroke subtypes.
• Compared with cardioembolic stroke, thrombotic/lacunar stroke was associated with lower readmission risk within 1 month (aHR, 0.66; 95% CI, 0.46-0.93) and from 1 month to 1 year (aHR, 0.78; 95% CI, 0.62-0.97), and hemorrhagic stroke was associated with lower risk from 1 month to 1 year (aHR, 0.60; 95% CI, 0.41-0.87).

IN PRACTICE:

“These results suggest that prevention strategies focused on cardiovascular and cerebrovascular health warrant further investigation, especially within the first year after incident stroke and perhaps particularly among individuals with an incident cardioembolic stroke,” the authors wrote.

SOURCE:

Kelly Sloane, MD, of the University of Pennsylvania Perelman School of Medicine in Philadelphia, led the study along with colleagues at the National Institute of Neurological Disorders and Stroke, Johns Hopkins University in Baltimore, and the University of North Carolina, Chapel Hill. The article was published online on January 5 in Neurology.

LIMITATIONS:

The ARIC study classification of stroke subtype grouped embolic strokes of undetermined source as thrombotic strokes, and investigators were unable to distinguish between the groups. In addition, there was no way to measure stroke severity, which could have played a role in readmission risk.

DISCLOSURES:

The study was funded by the National Heart, Lung, and Blood Institute, the National Institute of Neurological Disorders and Stroke, and the National Institutes of Health.

A version of this article appeared on Medscape.com.

TOPLINE: 

Among patients hospitalized with a first ischemic stroke, 80% were rehospitalized, primarily because of subsequent primary cardiovascular and cerebrovascular diagnoses.

METHODOLOGY:

• To gather information on post-stroke hospital admission, investigators followed 1412 participants (mean age, 72.4 years; 52.1% women, 35.3% Black individuals) from the Atherosclerosis Risk in Communities (ARIC) study who were living in Maryland, Minnesota, North Carolina, and Mississippi.
• Participants were recruited between 1987 and 1989 when they were 45-64 years old and were followed on an annual and then semiannual basis from the index discharge until discharge after their second hospitalization, death, or end of the study in December 2019.
• Specific diagnoses for each hospitalization were based on hospital records, discharge diagnoses, and annual and semiannual phone interviews.

TAKEAWAY: 

• During the study period, 1143 hospitalizations occurred over 41,849 person-months.
• 81% of participants were hospitalized over a maximum of 26.6 years of follow-up. Primary cardiovascular and cerebrovascular diagnoses were reported for half of readmissions.
• Over the follow-up period, compared with cardioembolic stroke, readmission risk was lower for thrombotic/lacunar stroke (adjusted hazard ratio [aHR], 0.82; 95% CI, 0.71-0.95) and hemorrhagic stroke (aHR, 0.74; 95% CI, 0.58-0.93). However, when adjusting for atrial fibrillation and competing risk for death, there were no significant differences between stroke subtypes.
• Compared with cardioembolic stroke, thrombotic/lacunar stroke was associated with lower readmission risk within 1 month (aHR, 0.66; 95% CI, 0.46-0.93) and from 1 month to 1 year (aHR, 0.78; 95% CI, 0.62-0.97), and hemorrhagic stroke was associated with lower risk from 1 month to 1 year (aHR, 0.60; 95% CI, 0.41-0.87).

IN PRACTICE:

“These results suggest that prevention strategies focused on cardiovascular and cerebrovascular health warrant further investigation, especially within the first year after incident stroke and perhaps particularly among individuals with an incident cardioembolic stroke,” the authors wrote.

SOURCE:

Kelly Sloane, MD, of the University of Pennsylvania Perelman School of Medicine in Philadelphia, led the study along with colleagues at the National Institute of Neurological Disorders and Stroke, Johns Hopkins University in Baltimore, and the University of North Carolina, Chapel Hill. The article was published online on January 5 in Neurology.

LIMITATIONS:

The ARIC study classification of stroke subtype grouped embolic strokes of undetermined source as thrombotic strokes, and investigators were unable to distinguish between the groups. In addition, there was no way to measure stroke severity, which could have played a role in readmission risk.

DISCLOSURES:

The study was funded by the National Heart, Lung, and Blood Institute, the National Institute of Neurological Disorders and Stroke, and the National Institutes of Health.

A version of this article appeared on Medscape.com.

TOPLINE: 

Among patients hospitalized with a first ischemic stroke, 80% were rehospitalized, primarily because of subsequent primary cardiovascular and cerebrovascular diagnoses.

METHODOLOGY:

• To gather information on post-stroke hospital admission, investigators followed 1412 participants (mean age, 72.4 years; 52.1% women, 35.3% Black individuals) from the Atherosclerosis Risk in Communities (ARIC) study who were living in Maryland, Minnesota, North Carolina, and Mississippi.
• Participants were recruited between 1987 and 1989 when they were 45-64 years old and were followed on an annual and then semiannual basis from the index discharge until discharge after their second hospitalization, death, or end of the study in December 2019.
• Specific diagnoses for each hospitalization were based on hospital records, discharge diagnoses, and annual and semiannual phone interviews.

TAKEAWAY: 

• During the study period, 1143 hospitalizations occurred over 41,849 person-months.
• 81% of participants were hospitalized over a maximum of 26.6 years of follow-up. Primary cardiovascular and cerebrovascular diagnoses were reported for half of readmissions.
• Over the follow-up period, compared with cardioembolic stroke, readmission risk was lower for thrombotic/lacunar stroke (adjusted hazard ratio [aHR], 0.82; 95% CI, 0.71-0.95) and hemorrhagic stroke (aHR, 0.74; 95% CI, 0.58-0.93). However, when adjusting for atrial fibrillation and competing risk for death, there were no significant differences between stroke subtypes.
• Compared with cardioembolic stroke, thrombotic/lacunar stroke was associated with lower readmission risk within 1 month (aHR, 0.66; 95% CI, 0.46-0.93) and from 1 month to 1 year (aHR, 0.78; 95% CI, 0.62-0.97), and hemorrhagic stroke was associated with lower risk from 1 month to 1 year (aHR, 0.60; 95% CI, 0.41-0.87).

IN PRACTICE:

“These results suggest that prevention strategies focused on cardiovascular and cerebrovascular health warrant further investigation, especially within the first year after incident stroke and perhaps particularly among individuals with an incident cardioembolic stroke,” the authors wrote.

SOURCE:

Kelly Sloane, MD, of the University of Pennsylvania Perelman School of Medicine in Philadelphia, led the study along with colleagues at the National Institute of Neurological Disorders and Stroke, Johns Hopkins University in Baltimore, and the University of North Carolina, Chapel Hill. The article was published online on January 5 in Neurology.

LIMITATIONS:

The ARIC study classification of stroke subtype grouped embolic strokes of undetermined source as thrombotic strokes, and investigators were unable to distinguish between the groups. In addition, there was no way to measure stroke severity, which could have played a role in readmission risk.

DISCLOSURES:

The study was funded by the National Heart, Lung, and Blood Institute, the National Institute of Neurological Disorders and Stroke, and the National Institutes of Health.

A version of this article appeared on Medscape.com.

TOPLINE:

Patients undergoing transcatheter aortic valve replacement (TAVR) have a higher risk for stroke for up to 2 years compared with an age- and sex-matched population, after which their risks are comparable, results of a large Swiss registry study suggest.

METHODOLOGY:

• The study included 11,957 patients from the prospective SwissTAVI Registry, an ongoing mandatory cohort study enrolling consecutive patients undergoing TAVR in Switzerland.
• The study population, which had a mean age of 81.8 years and mean Society of Thoracic Surgeons Predicted Risk of Mortality (STS PROM) of 4.62, with 11.8% having a history of cerebrovascular accident (CVA) and 32.3% a history of atrial fibrillation, underwent TAVR at 15 centers between February 2011 and June 2021.
• The primary outcome was the incidence of stroke, with secondary outcomes including the incidence of CVA, a composite of stroke and transient ischemic attack (TIA).
• Researchers calculated standardized stroke ratios (SSRs) and compared stroke trends in patients undergoing TAVR with those of an age- and sex-matched general population in Switzerland derived from the 2019 Global Burden of Disease (GBD) study.

TAKEAWAY:

• The 30-day incidence rates of CVA and stroke were 3.3% and 3.0%, respectively, with the highest risk within the first 48 hours post TAVR, accounting for 69% of these events.
• After excluding 30-day events, the 1-year incidence rates of CVA and stroke were 1.7% and 1.4%, respectively, followed by an annual stroke incidence of 1.2%, 0.8%, 0.9%, and 0.7% in the second, third, fourth, and fifth years post TAVR, respectively.
• Only increased age and moderate/severe paravalvular leakage (PVL) at discharge were associated with an increased risk for early stroke (up to 30 days post TAVR), whereas dyslipidemia and history of atrial fibrillation and of CVA were associated with an increased risk for late stroke (30 days to 5 years after TAVR).
• SSR in the study population returned to a level comparable to that expected in the general Swiss population after 2 years and through to 5 years post-TAVR.

IN PRACTICE:

Although the study results “are reassuring” with respect to stroke risk beyond 2 years post TAVR, “our findings underscore the continued efforts of stroke-prevention measures” early and longer term, wrote the authors.

In an accompanying editorial, Lauge Østergaard, MD, PhD, Department of Cardiology, University of Copenhagen, Denmark, noted the study suggests reduced PVL could lower the risk for early stroke following TAVR and “highlights how assessment of usual risk factors (dyslipidemia and atrial fibrillation) could help reduce the burden of stroke in the long term.”

SOURCE:

The study was carried out by Taishi Okuno, MD, Department of Cardiology, Bern University Hospital, University of Bern, Switzerland, and colleagues. It was published online in the Journal of the American College of Cardiology (JACC): Cardiovascular Interventions.

LIMITATIONS:

The study couldn’t investigate the association between antithrombotic regimens and the risk for CVA. Definitions of CVA in the SwissTAVI Registry might differ from those used in the GBD study from which the matched population data were derived. The general population wasn’t matched on comorbidities usually associated with elevated stroke risk, which may have led to underestimation of stroke. As the mean age in the study was 82 years, results may not be extrapolated to a younger population.

DISCLOSURES:

The SwissTAVI registry is supported by the Swiss Heart Foundation, Swiss Working Group of Interventional Cardiology and Acute Coronary Syndromes, Medtronic, Edwards Lifesciences, Boston Scientific/Symetis, JenaValve, and St. Jude Medical. Dr. Okuno has no relevant conflicts of interest; see paper for disclosures of other study authors. Dr. Østergaard has received an independent research grant from the Novo Nordisk Foundation.

A version of this article appeared on Medscape.com.

TOPLINE:

Patients undergoing transcatheter aortic valve replacement (TAVR) have a higher risk for stroke for up to 2 years compared with an age- and sex-matched population, after which their risks are comparable, results of a large Swiss registry study suggest.

METHODOLOGY:

• The study included 11,957 patients from the prospective SwissTAVI Registry, an ongoing mandatory cohort study enrolling consecutive patients undergoing TAVR in Switzerland.
• The study population, which had a mean age of 81.8 years and mean Society of Thoracic Surgeons Predicted Risk of Mortality (STS PROM) of 4.62, with 11.8% having a history of cerebrovascular accident (CVA) and 32.3% a history of atrial fibrillation, underwent TAVR at 15 centers between February 2011 and June 2021.
• The primary outcome was the incidence of stroke, with secondary outcomes including the incidence of CVA, a composite of stroke and transient ischemic attack (TIA).
• Researchers calculated standardized stroke ratios (SSRs) and compared stroke trends in patients undergoing TAVR with those of an age- and sex-matched general population in Switzerland derived from the 2019 Global Burden of Disease (GBD) study.

TAKEAWAY:

• The 30-day incidence rates of CVA and stroke were 3.3% and 3.0%, respectively, with the highest risk within the first 48 hours post TAVR, accounting for 69% of these events.
• After excluding 30-day events, the 1-year incidence rates of CVA and stroke were 1.7% and 1.4%, respectively, followed by an annual stroke incidence of 1.2%, 0.8%, 0.9%, and 0.7% in the second, third, fourth, and fifth years post TAVR, respectively.
• Only increased age and moderate/severe paravalvular leakage (PVL) at discharge were associated with an increased risk for early stroke (up to 30 days post TAVR), whereas dyslipidemia and history of atrial fibrillation and of CVA were associated with an increased risk for late stroke (30 days to 5 years after TAVR).
• SSR in the study population returned to a level comparable to that expected in the general Swiss population after 2 years and through to 5 years post-TAVR.

IN PRACTICE:

Although the study results “are reassuring” with respect to stroke risk beyond 2 years post TAVR, “our findings underscore the continued efforts of stroke-prevention measures” early and longer term, wrote the authors.

In an accompanying editorial, Lauge Østergaard, MD, PhD, Department of Cardiology, University of Copenhagen, Denmark, noted the study suggests reduced PVL could lower the risk for early stroke following TAVR and “highlights how assessment of usual risk factors (dyslipidemia and atrial fibrillation) could help reduce the burden of stroke in the long term.”

SOURCE:

The study was carried out by Taishi Okuno, MD, Department of Cardiology, Bern University Hospital, University of Bern, Switzerland, and colleagues. It was published online in the Journal of the American College of Cardiology (JACC): Cardiovascular Interventions.

LIMITATIONS:

The study couldn’t investigate the association between antithrombotic regimens and the risk for CVA. Definitions of CVA in the SwissTAVI Registry might differ from those used in the GBD study from which the matched population data were derived. The general population wasn’t matched on comorbidities usually associated with elevated stroke risk, which may have led to underestimation of stroke. As the mean age in the study was 82 years, results may not be extrapolated to a younger population.

DISCLOSURES:

The SwissTAVI registry is supported by the Swiss Heart Foundation, Swiss Working Group of Interventional Cardiology and Acute Coronary Syndromes, Medtronic, Edwards Lifesciences, Boston Scientific/Symetis, JenaValve, and St. Jude Medical. Dr. Okuno has no relevant conflicts of interest; see paper for disclosures of other study authors. Dr. Østergaard has received an independent research grant from the Novo Nordisk Foundation.

A version of this article appeared on Medscape.com.

TOPLINE:

Patients undergoing transcatheter aortic valve replacement (TAVR) have a higher risk for stroke for up to 2 years compared with an age- and sex-matched population, after which their risks are comparable, results of a large Swiss registry study suggest.

METHODOLOGY:

• The study included 11,957 patients from the prospective SwissTAVI Registry, an ongoing mandatory cohort study enrolling consecutive patients undergoing TAVR in Switzerland.
• The study population, which had a mean age of 81.8 years and mean Society of Thoracic Surgeons Predicted Risk of Mortality (STS PROM) of 4.62, with 11.8% having a history of cerebrovascular accident (CVA) and 32.3% a history of atrial fibrillation, underwent TAVR at 15 centers between February 2011 and June 2021.
• The primary outcome was the incidence of stroke, with secondary outcomes including the incidence of CVA, a composite of stroke and transient ischemic attack (TIA).
• Researchers calculated standardized stroke ratios (SSRs) and compared stroke trends in patients undergoing TAVR with those of an age- and sex-matched general population in Switzerland derived from the 2019 Global Burden of Disease (GBD) study.

TAKEAWAY:

• The 30-day incidence rates of CVA and stroke were 3.3% and 3.0%, respectively, with the highest risk within the first 48 hours post TAVR, accounting for 69% of these events.
• After excluding 30-day events, the 1-year incidence rates of CVA and stroke were 1.7% and 1.4%, respectively, followed by an annual stroke incidence of 1.2%, 0.8%, 0.9%, and 0.7% in the second, third, fourth, and fifth years post TAVR, respectively.
• Only increased age and moderate/severe paravalvular leakage (PVL) at discharge were associated with an increased risk for early stroke (up to 30 days post TAVR), whereas dyslipidemia and history of atrial fibrillation and of CVA were associated with an increased risk for late stroke (30 days to 5 years after TAVR).
• SSR in the study population returned to a level comparable to that expected in the general Swiss population after 2 years and through to 5 years post-TAVR.

IN PRACTICE:

Although the study results “are reassuring” with respect to stroke risk beyond 2 years post TAVR, “our findings underscore the continued efforts of stroke-prevention measures” early and longer term, wrote the authors.

In an accompanying editorial, Lauge Østergaard, MD, PhD, Department of Cardiology, University of Copenhagen, Denmark, noted the study suggests reduced PVL could lower the risk for early stroke following TAVR and “highlights how assessment of usual risk factors (dyslipidemia and atrial fibrillation) could help reduce the burden of stroke in the long term.”

SOURCE:

The study was carried out by Taishi Okuno, MD, Department of Cardiology, Bern University Hospital, University of Bern, Switzerland, and colleagues. It was published online in the Journal of the American College of Cardiology (JACC): Cardiovascular Interventions.

LIMITATIONS:

The study couldn’t investigate the association between antithrombotic regimens and the risk for CVA. Definitions of CVA in the SwissTAVI Registry might differ from those used in the GBD study from which the matched population data were derived. The general population wasn’t matched on comorbidities usually associated with elevated stroke risk, which may have led to underestimation of stroke. As the mean age in the study was 82 years, results may not be extrapolated to a younger population.

DISCLOSURES:

The SwissTAVI registry is supported by the Swiss Heart Foundation, Swiss Working Group of Interventional Cardiology and Acute Coronary Syndromes, Medtronic, Edwards Lifesciences, Boston Scientific/Symetis, JenaValve, and St. Jude Medical. Dr. Okuno has no relevant conflicts of interest; see paper for disclosures of other study authors. Dr. Østergaard has received an independent research grant from the Novo Nordisk Foundation.

A version of this article appeared on Medscape.com.

ORLANDO — Combining an enzyme-inducing antiseizure medication with a direct-acting oral anticoagulant (DOAC) does not significantly increase the risk of thromboembolic events in patients with epilepsy, preliminary results of a new study show.

These new data are important, “particularly when we’re talking about a more global perspective, given the vital role of enzyme-inducing antiseizure medications in epilepsy care across many middle- and low-income countries where they may be the only readily available treatment options,” said study investigator Emily K. Acton, PhD candidate in epidemiology and a medical student, University of Pennsylvania Perelman School of Medicine, Philadelphia, and University of Illinois College of Medicine, Chicago. 

The findings also suggest that use of enzyme-inducing antiseizure medication with DOACs may be associated with a reduction in major bleeding events, although Ms. Acton stressed this requires more research.

The findings were presented at the American Epilepsy Society annual meeting.
 

Important Implications

Enzyme-inducing antiseizure medications may induce key drug metabolizing enzymes that result in wide-ranging interactions, Ms. Acton told this news organization. “But, in many cases, the clinical significance of these pharmacokinetic interactions is not completely understood.”

This has important implications for managing anticoagulation, said Ms. Acton. “The ease of DOAC use, and growing evidence of the drugs’ safety and efficacy compared to vitamin K antagonists, has led to widespread shifts in clinical practice towards DOACs.”

Due to the relative novelty of DOACs, their interaction profiles have been less than complete, she explained. Evidence that enzyme-inducing antiseizure medications may reduce absorption and accelerate metabolism of DOACs, potentially lowering DOAC levels and elevating thromboembolism risk, comes mainly from in vitro and animal studies.

“Research in humans is lacking and complicated in interpretation by inconsistent findings and methodological limitations,” she said.

The investigators wanted to address the “clinical uncertainty” surrounding the real-world relevance of enzyme-inducing antiseizure medications and DOAC interactions but conducting a randomized trial “would be neither feasible nor ethical,” said Ms. Acton. 

Using healthcare claims data from October 2010 to September 2021, the researchers conducted an active comparator, new-user cohort study among a nationally representative sample of adults with epilepsy who had been co-prescribed these drugs. 

They compared thromboembolic and major bleeding event rates between exposure to DOACs with enzyme-inducing antiseizure medications vs exposure to DOACs with non-enzyme inducing antiseizure medications.

Enzyme-inducing antiseizure medications included in the study were carbamazepine, oxcarbazepine, phenobarbital, phenytoin, primidone, and topiramate. Non-enzyme-inducing antiseizure medications included gabapentin, lacosamide, lamotrigine, levetiracetam, and pregabalin.

The researchers used data-adaptive high-dimensional propensity score matching to control for “hundreds and hundreds” of observed confounders, and proxies for unobserved confounders, said Ms. Acton. They identified outcomes based on validated diagnostic coding algorithms for thromboembolic and major bleeding events and estimated adjusted hazard ratios (aHRs) using Cox proportional hazard models with robust variance estimators to account for clustering within matched pairs.
 

Reduced Risk of Major Bleeding 

Outcomes were analyzed in three separate cohorts. These included patients on DOACs for any indication (indication-agnostic); those on DOACs for atrial fibrillation (AF); and those taking DOACs for deep vein thrombus/pulmonary embolism (DVT/PE).

In the indication-agnostic analysis, the investigators examined thromboembolic events among 5989 episodes in patients taking both DOACs and enzyme-inducing antiseizure medications, compared witha reference group of 14,671 episodes in patients taking DOACs and non-enzyme-inducing antiseizure medications.

The reference group was generally older and had a greater prevalence of a number of major comorbidities compared with the exposed group, noted Ms. Acton.

For the indication-agnostic analysis, the aHR was 1.11 (95% CI 0.89-1.39). Results were similar for the AF indication (aHR 1.10; 95% CI 0.82-1.46) and for the DVT/PE indication (aHR 1.11; 95% CI 0.81-1.51).

“This research provides large-scale, real-world evidence enzyme-inducing antiseizure medication use alongside DOACs does not significantly elevate risk of thromboembolic events among a nationally representative epilepsy population,” said Ms. Acton.

However, “it’s always important to consider risk factors for thromboembolic and bleeding events at the level of the individual patient,” she added.

With respect to major bleeding events, there was a slightly reduced risk in the exposed group, specifically in the analysis of subjects with atrial fibrillation, where the aHR was 0.63 (95% CI 0.44-0.89).

“A potential explanation may be pharmacokinetic interaction with enzyme-inducing antiseizure medications occurring to a degree that lowers DOAC levels without necessarily negating therapeutic effects,” said Ms. Acton.

However, she cautioned that more research is needed.

As for the differential potency among the various enzyme-inducing antiseizure medications studied, Ms. Acton said results from a secondary analysis in the atrial fibrillation assessment that removed the potentially less potent enzyme inducers, oxcarbazepine and topiramate, didn’t significantly change the study results.
 

‘Really Great News’

Commenting on the findings for this news organization, epilepsy expert Daniel M. Goldenholz, MD, PhD, assistant professor of Neurology, Harvard Beth Israel Deaconess Medical Center, Boston, Massachusetts, said the finding of no meaningful difference between DOAC plus enzyme-inducing medications vs DOACs plus non-enzyme-inducing medications is encouraging.

“This study asks a very important question at the population level and appropriately tries to control for present and hidden factors using a propensity matching approach,” he said.

The fact that the data support no difference in terms of thromboembolic events “is really great news” for patients taking an enzyme-inducing antiseizure medication who need to use a DOAC, he said.

While some patients or clinicians might consider transitioning off an enzyme-inducing antiseizure medication, this can lead to new side effects and potentially higher drug costs. “Knowing that a transition may be unnecessary is exciting,” said Dr. Goldenholz.

However, he’s concerned the 1.5-year observation period may not be long enough to see a true effect of these drug combinations.

He also noted that due to the “theoretical higher risk,” patients combining DOACs with enzyme-inducing drugs typically need extra monitoring, which may be less practical outside the US. This suggests “the result may not necessarily generalize outside high-income countries,” he said.

Dr. Goldenholz emphasized that the data are preliminary. “As always, I look forward to a full peer-reviewed study before forming final conclusions.”

The study was supported by the US Department of Health and Human Services’ National Institute of Neurological Disorders and Stroke.

Ms. Acton and Dr. Goldenholz report no relevant financial relationships.

A version of this article appeared on Medscape.com.

ORLANDO — Combining an enzyme-inducing antiseizure medication with a direct-acting oral anticoagulant (DOAC) does not significantly increase the risk of thromboembolic events in patients with epilepsy, preliminary results of a new study show.

These new data are important, “particularly when we’re talking about a more global perspective, given the vital role of enzyme-inducing antiseizure medications in epilepsy care across many middle- and low-income countries where they may be the only readily available treatment options,” said study investigator Emily K. Acton, PhD candidate in epidemiology and a medical student, University of Pennsylvania Perelman School of Medicine, Philadelphia, and University of Illinois College of Medicine, Chicago. 

The findings also suggest that use of enzyme-inducing antiseizure medication with DOACs may be associated with a reduction in major bleeding events, although Ms. Acton stressed this requires more research.

The findings were presented at the American Epilepsy Society annual meeting.
 

Important Implications

Enzyme-inducing antiseizure medications may induce key drug metabolizing enzymes that result in wide-ranging interactions, Ms. Acton told this news organization. “But, in many cases, the clinical significance of these pharmacokinetic interactions is not completely understood.”

This has important implications for managing anticoagulation, said Ms. Acton. “The ease of DOAC use, and growing evidence of the drugs’ safety and efficacy compared to vitamin K antagonists, has led to widespread shifts in clinical practice towards DOACs.”

Due to the relative novelty of DOACs, their interaction profiles have been less than complete, she explained. Evidence that enzyme-inducing antiseizure medications may reduce absorption and accelerate metabolism of DOACs, potentially lowering DOAC levels and elevating thromboembolism risk, comes mainly from in vitro and animal studies.

“Research in humans is lacking and complicated in interpretation by inconsistent findings and methodological limitations,” she said.

The investigators wanted to address the “clinical uncertainty” surrounding the real-world relevance of enzyme-inducing antiseizure medications and DOAC interactions but conducting a randomized trial “would be neither feasible nor ethical,” said Ms. Acton. 

Using healthcare claims data from October 2010 to September 2021, the researchers conducted an active comparator, new-user cohort study among a nationally representative sample of adults with epilepsy who had been co-prescribed these drugs. 

They compared thromboembolic and major bleeding event rates between exposure to DOACs with enzyme-inducing antiseizure medications vs exposure to DOACs with non-enzyme inducing antiseizure medications.

Enzyme-inducing antiseizure medications included in the study were carbamazepine, oxcarbazepine, phenobarbital, phenytoin, primidone, and topiramate. Non-enzyme-inducing antiseizure medications included gabapentin, lacosamide, lamotrigine, levetiracetam, and pregabalin.

The researchers used data-adaptive high-dimensional propensity score matching to control for “hundreds and hundreds” of observed confounders, and proxies for unobserved confounders, said Ms. Acton. They identified outcomes based on validated diagnostic coding algorithms for thromboembolic and major bleeding events and estimated adjusted hazard ratios (aHRs) using Cox proportional hazard models with robust variance estimators to account for clustering within matched pairs.
 

Reduced Risk of Major Bleeding 

Outcomes were analyzed in three separate cohorts. These included patients on DOACs for any indication (indication-agnostic); those on DOACs for atrial fibrillation (AF); and those taking DOACs for deep vein thrombus/pulmonary embolism (DVT/PE).

In the indication-agnostic analysis, the investigators examined thromboembolic events among 5989 episodes in patients taking both DOACs and enzyme-inducing antiseizure medications, compared witha reference group of 14,671 episodes in patients taking DOACs and non-enzyme-inducing antiseizure medications.

The reference group was generally older and had a greater prevalence of a number of major comorbidities compared with the exposed group, noted Ms. Acton.

For the indication-agnostic analysis, the aHR was 1.11 (95% CI 0.89-1.39). Results were similar for the AF indication (aHR 1.10; 95% CI 0.82-1.46) and for the DVT/PE indication (aHR 1.11; 95% CI 0.81-1.51).

“This research provides large-scale, real-world evidence enzyme-inducing antiseizure medication use alongside DOACs does not significantly elevate risk of thromboembolic events among a nationally representative epilepsy population,” said Ms. Acton.

However, “it’s always important to consider risk factors for thromboembolic and bleeding events at the level of the individual patient,” she added.

With respect to major bleeding events, there was a slightly reduced risk in the exposed group, specifically in the analysis of subjects with atrial fibrillation, where the aHR was 0.63 (95% CI 0.44-0.89).

“A potential explanation may be pharmacokinetic interaction with enzyme-inducing antiseizure medications occurring to a degree that lowers DOAC levels without necessarily negating therapeutic effects,” said Ms. Acton.

However, she cautioned that more research is needed.

As for the differential potency among the various enzyme-inducing antiseizure medications studied, Ms. Acton said results from a secondary analysis in the atrial fibrillation assessment that removed the potentially less potent enzyme inducers, oxcarbazepine and topiramate, didn’t significantly change the study results.
 

‘Really Great News’

Commenting on the findings for this news organization, epilepsy expert Daniel M. Goldenholz, MD, PhD, assistant professor of Neurology, Harvard Beth Israel Deaconess Medical Center, Boston, Massachusetts, said the finding of no meaningful difference between DOAC plus enzyme-inducing medications vs DOACs plus non-enzyme-inducing medications is encouraging.

“This study asks a very important question at the population level and appropriately tries to control for present and hidden factors using a propensity matching approach,” he said.

The fact that the data support no difference in terms of thromboembolic events “is really great news” for patients taking an enzyme-inducing antiseizure medication who need to use a DOAC, he said.

While some patients or clinicians might consider transitioning off an enzyme-inducing antiseizure medication, this can lead to new side effects and potentially higher drug costs. “Knowing that a transition may be unnecessary is exciting,” said Dr. Goldenholz.

However, he’s concerned the 1.5-year observation period may not be long enough to see a true effect of these drug combinations.

He also noted that due to the “theoretical higher risk,” patients combining DOACs with enzyme-inducing drugs typically need extra monitoring, which may be less practical outside the US. This suggests “the result may not necessarily generalize outside high-income countries,” he said.

Dr. Goldenholz emphasized that the data are preliminary. “As always, I look forward to a full peer-reviewed study before forming final conclusions.”

The study was supported by the US Department of Health and Human Services’ National Institute of Neurological Disorders and Stroke.

Ms. Acton and Dr. Goldenholz report no relevant financial relationships.

A version of this article appeared on Medscape.com.

ORLANDO — Combining an enzyme-inducing antiseizure medication with a direct-acting oral anticoagulant (DOAC) does not significantly increase the risk of thromboembolic events in patients with epilepsy, preliminary results of a new study show.

These new data are important, “particularly when we’re talking about a more global perspective, given the vital role of enzyme-inducing antiseizure medications in epilepsy care across many middle- and low-income countries where they may be the only readily available treatment options,” said study investigator Emily K. Acton, PhD candidate in epidemiology and a medical student, University of Pennsylvania Perelman School of Medicine, Philadelphia, and University of Illinois College of Medicine, Chicago. 

The findings also suggest that use of enzyme-inducing antiseizure medication with DOACs may be associated with a reduction in major bleeding events, although Ms. Acton stressed this requires more research.

The findings were presented at the American Epilepsy Society annual meeting.
 

Important Implications

Enzyme-inducing antiseizure medications may induce key drug metabolizing enzymes that result in wide-ranging interactions, Ms. Acton told this news organization. “But, in many cases, the clinical significance of these pharmacokinetic interactions is not completely understood.”

This has important implications for managing anticoagulation, said Ms. Acton. “The ease of DOAC use, and growing evidence of the drugs’ safety and efficacy compared to vitamin K antagonists, has led to widespread shifts in clinical practice towards DOACs.”

Due to the relative novelty of DOACs, their interaction profiles have been less than complete, she explained. Evidence that enzyme-inducing antiseizure medications may reduce absorption and accelerate metabolism of DOACs, potentially lowering DOAC levels and elevating thromboembolism risk, comes mainly from in vitro and animal studies.

“Research in humans is lacking and complicated in interpretation by inconsistent findings and methodological limitations,” she said.

The investigators wanted to address the “clinical uncertainty” surrounding the real-world relevance of enzyme-inducing antiseizure medications and DOAC interactions but conducting a randomized trial “would be neither feasible nor ethical,” said Ms. Acton. 

Using healthcare claims data from October 2010 to September 2021, the researchers conducted an active comparator, new-user cohort study among a nationally representative sample of adults with epilepsy who had been co-prescribed these drugs. 

They compared thromboembolic and major bleeding event rates between exposure to DOACs with enzyme-inducing antiseizure medications vs exposure to DOACs with non-enzyme inducing antiseizure medications.

Enzyme-inducing antiseizure medications included in the study were carbamazepine, oxcarbazepine, phenobarbital, phenytoin, primidone, and topiramate. Non-enzyme-inducing antiseizure medications included gabapentin, lacosamide, lamotrigine, levetiracetam, and pregabalin.

The researchers used data-adaptive high-dimensional propensity score matching to control for “hundreds and hundreds” of observed confounders, and proxies for unobserved confounders, said Ms. Acton. They identified outcomes based on validated diagnostic coding algorithms for thromboembolic and major bleeding events and estimated adjusted hazard ratios (aHRs) using Cox proportional hazard models with robust variance estimators to account for clustering within matched pairs.
 

Reduced Risk of Major Bleeding 

Outcomes were analyzed in three separate cohorts. These included patients on DOACs for any indication (indication-agnostic); those on DOACs for atrial fibrillation (AF); and those taking DOACs for deep vein thrombus/pulmonary embolism (DVT/PE).

In the indication-agnostic analysis, the investigators examined thromboembolic events among 5989 episodes in patients taking both DOACs and enzyme-inducing antiseizure medications, compared witha reference group of 14,671 episodes in patients taking DOACs and non-enzyme-inducing antiseizure medications.

The reference group was generally older and had a greater prevalence of a number of major comorbidities compared with the exposed group, noted Ms. Acton.

For the indication-agnostic analysis, the aHR was 1.11 (95% CI 0.89-1.39). Results were similar for the AF indication (aHR 1.10; 95% CI 0.82-1.46) and for the DVT/PE indication (aHR 1.11; 95% CI 0.81-1.51).

“This research provides large-scale, real-world evidence enzyme-inducing antiseizure medication use alongside DOACs does not significantly elevate risk of thromboembolic events among a nationally representative epilepsy population,” said Ms. Acton.

However, “it’s always important to consider risk factors for thromboembolic and bleeding events at the level of the individual patient,” she added.

With respect to major bleeding events, there was a slightly reduced risk in the exposed group, specifically in the analysis of subjects with atrial fibrillation, where the aHR was 0.63 (95% CI 0.44-0.89).

“A potential explanation may be pharmacokinetic interaction with enzyme-inducing antiseizure medications occurring to a degree that lowers DOAC levels without necessarily negating therapeutic effects,” said Ms. Acton.

However, she cautioned that more research is needed.

As for the differential potency among the various enzyme-inducing antiseizure medications studied, Ms. Acton said results from a secondary analysis in the atrial fibrillation assessment that removed the potentially less potent enzyme inducers, oxcarbazepine and topiramate, didn’t significantly change the study results.
 

‘Really Great News’

Commenting on the findings for this news organization, epilepsy expert Daniel M. Goldenholz, MD, PhD, assistant professor of Neurology, Harvard Beth Israel Deaconess Medical Center, Boston, Massachusetts, said the finding of no meaningful difference between DOAC plus enzyme-inducing medications vs DOACs plus non-enzyme-inducing medications is encouraging.

“This study asks a very important question at the population level and appropriately tries to control for present and hidden factors using a propensity matching approach,” he said.

The fact that the data support no difference in terms of thromboembolic events “is really great news” for patients taking an enzyme-inducing antiseizure medication who need to use a DOAC, he said.

While some patients or clinicians might consider transitioning off an enzyme-inducing antiseizure medication, this can lead to new side effects and potentially higher drug costs. “Knowing that a transition may be unnecessary is exciting,” said Dr. Goldenholz.

However, he’s concerned the 1.5-year observation period may not be long enough to see a true effect of these drug combinations.

He also noted that due to the “theoretical higher risk,” patients combining DOACs with enzyme-inducing drugs typically need extra monitoring, which may be less practical outside the US. This suggests “the result may not necessarily generalize outside high-income countries,” he said.

Dr. Goldenholz emphasized that the data are preliminary. “As always, I look forward to a full peer-reviewed study before forming final conclusions.”

The study was supported by the US Department of Health and Human Services’ National Institute of Neurological Disorders and Stroke.

Ms. Acton and Dr. Goldenholz report no relevant financial relationships.

A version of this article appeared on Medscape.com.