Pauline Anderson

Treatment with the investigational monoclonal antibody drug batoclimab significantly improved symptoms in patients with antibody-positive generalized myasthenia gravis, data from a new phase 3 study showed.

After 6 weeks of treatment, patients reported nearly 60% sustained improvement in daily activities and a rapid onset of action from batoclimab, a neonatal crystallizable fragment receptor (FcRn) antagonist.

The clinical effects and the extent of immunoglobulin G (IgG) reduction in this study were similar to those previously reported for efgartigimod and rozanolixizumab, two other FcRn antagonists, the investigators noted, adding that larger studies are needed to better understand the safety profile of batoclimab.

“While most generalized myasthenia gravis patients can achieve good disease control through conventional immunotherapy, there are still unmet needs with this disease,” said study investigator Chongbo Zhao, MD, National Center for Neurological Disorders, Huashan Rare Disease Centre, Department of Neurology, Huashan Hospital of Fudan University, Shanghai, China.

The findings were published online in JAMA Neurology.
 

Unmet Need

A rare chronic disease, myasthenia gravis is caused by autoantibodies that disrupt the neuromuscular junction, most commonly against the nicotinic acetylcholine receptor (AChR). This can cause a variety of symptoms, including difficulty swallowing, chewing, and talking, as well as severe, sometimes life-threatening, muscle weakness.

The estimated global prevalence of myasthenia gravis is 15-25 per 100,000, with cases doubling in the past 20 years.

Treatment for myasthenia gravis typically includes immune-suppressing drugs. But research suggests almost half of patients with generalized myasthenia gravis don’t achieve an adequate response or are intolerant to these treatments, and some therapies are costly or not readily accessible.

“Our treatment goal has evolved from saving patients to improving their quality of life, so we still need to explore safer and more effective novel treatment methods,” Dr. Zhao said.

Batoclimab is a fully humanized monoclonal IgG antibody that binds to FcRn and accelerates clearance of harmful IgG. A phase 2 trial provided preliminary evidence to support the efficacy of this agent in Chinese patients with generalized myasthenia gravis.

The current double-blind phase 3 trial included 132 adult patients (mean age, 44 years; 67% female) of Chinese Han ethnicity with generalized myasthenia gravis at 27 centers in China. Participants had a mean Myasthenia Gravis Activities of Daily Living (MG-ADL) score of 8.4 at baseline, and all but one was positive for AChR or muscle-specific kinase (MuSK) antibodies.

The treatment group received weekly subcutaneous injections of batoclimab at 680 mg for 6 weeks, followed by 4 weeks of observation. The control group received a placebo with the same treatment and follow-up schedule.

All patients received standard of care in addition to the assigned treatment, but changes in dosage and/or dosing frequency were not permitted. Patients received a second cycle if they still required treatment.
 

Bests Placebo

Overall, 90% of participants completed all six doses in cycle 1. The second treatment cycle was conducted in 115 patients, with 88% completing all six doses.

Patients were evaluated at baseline and then weekly for MG-ADL, Quantitative Myasthenia Gravis (QMG), Myasthenia Gravis Composite, and the 15-item revised version of the Myasthenia Gravis Quality of Life.

Sustained MG-ADL improvement — the primary outcome — was significantly higher in the batoclimab group compared with placebo (58% vs 31%, respectively; odds ratio, 3.45; P = .001).

While the rate of sustained MG-ADL improvement with batoclimab was lower than that reported for efgartigimod (68%) in a previous trial, that was primarily because of the more stringent definition of sustained MG-ADL improvement (three-point reduction vs two-point reduction from baseline), investigators said.

In the current trial, batoclimab had a rapid onset of action, with scores diverging between the treatment and placebo groups as early as the second week of therapy.

In the second treatment cycle, batoclimab once again outperformed placebo in sustained MG-ADL improvement (63% vs 36%, respectively; P = .002).

Batoclimab also bested placebo on secondary outcomes, including sustained QMG improvement (64% vs 41%; P = .008) and percent of patients achieving minimal symptom expression (25% vs 5%; P = .004).

Results of all subgroup analyses, including by age groups, sex, body weight, body mass index, and MG Foundation of America clinical classification, were consistent with those of the main analysis. The efficacy of batoclimab was also supported by all sensitivity analyses, underscoring the robustness of results.

Batoclimab led to a rapid and sustained reduction in serum AChR antibody levels, with a median reduction of 81% at week 6.
 

Well Tolerated

On discontinuation of batoclimab, serum total IgG returned to a level comparable with the baseline after 4 weeks. Reversibility of the drug’s effect is important considering the risk for infection from prolonged immune suppression, the authors noted.

The rate of peripheral edema was significantly higher in the treatment than in the placebo groups (39% vs 5%), but all cases were mild or moderate and deemed not clinically significant. The treatment group also had higher rates of upper respiratory tract infections (36% vs 22%) and of urinary tract infections (19% vs 15%).

“Although the incidence of upper respiratory tract and urinary tract infections was higher in the batoclimab group numerically, these were mild infections that did not require special treatment, so this is not a concern,” said Dr. Zhao.

Plasma albumin levels in the batoclimab group decreased significantly throughout the treatment cycle, starting at week 1 and reaching a decline of up to 31% at week 6. These levels increased rapidly toward baseline after treatment discontinuation.

High cholesterol levels were noted in the batoclimab group, plateauing by week 6. But levels returned to near baseline levels within 4 weeks after the final dose, and there were no serious related adverse reactions.

The rate of headache was slightly higher in the treatment group (6% vs 5% for placebo). “This finding may seem minor but could potentially translate into improved adherence in daily practice settings,” the authors wrote.

In previous studies, the efficacy of FcRn inhibitors in the Asian population was only examined in subgroup analyses with limited subjects. Finding an effective FcRn antagonist for China and surrounding regions is particularly important “considering the high mortality rate in hospitalized generalized myasthenia gravis patients in China,” the researchers noted.

The trial included only two treatment cycles, although results of an open-label extension trial examining longer-term efficacy of batoclimab should be available by the end of this year, said Dr. Zhao.

The trial was also not designed to investigate long-term safety, particularly infections and cardiovascular events. Only one study subject was negative for AChR or MuSK antibodies, which prevented researchers from assessing the drug’s efficacy in this subpopulation.
 

Questions Remain

Commenting on the study, Fredrik Piehl, MD, PhD, professor of neurology, Karolinska Institute, Stockholm, Sweden , said that recent studies of the two other FcRn antagonists were short-term and had limited long-term data. “We don’t know how valuable they may be for continued treatment,” Dr. Piehl said.

It’s also unclear how this new treatment modality compares with existing and emerging drug strategies in terms of the long-term benefit-risk balance, he added.

The rate of adverse events with batoclimab was high compared with placebo in this study and higher than in earlier studies of efgartigimod, Dr. Piehl noted.

“In this study, almost twice as many reported adverse events in the active arm compared with controls, while these differences tended to be smaller in previously reported trials,” he said.

The trial was funded by Nona Biosciences (Suzhou). Dr. Zhao reported being a full-time employee of Nona Biosciences (Suzhou), a subsidiary of Harbour BioMed Inc. He also reported receiving advisory board/consultant fees from Nona Biosciences, Roche, Sanofi, and Zailab outside the submitted work. Dr. Piehl has received research grants from Janssen, Merck KGaA, and UCB; and fees for serving on DMC in clinical trials with Chugai, Lundbeck, and Roche; and preparation of expert witness statement for Novartis.

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

Treatment with the investigational monoclonal antibody drug batoclimab significantly improved symptoms in patients with antibody-positive generalized myasthenia gravis, data from a new phase 3 study showed.

After 6 weeks of treatment, patients reported nearly 60% sustained improvement in daily activities and a rapid onset of action from batoclimab, a neonatal crystallizable fragment receptor (FcRn) antagonist.

The clinical effects and the extent of immunoglobulin G (IgG) reduction in this study were similar to those previously reported for efgartigimod and rozanolixizumab, two other FcRn antagonists, the investigators noted, adding that larger studies are needed to better understand the safety profile of batoclimab.

“While most generalized myasthenia gravis patients can achieve good disease control through conventional immunotherapy, there are still unmet needs with this disease,” said study investigator Chongbo Zhao, MD, National Center for Neurological Disorders, Huashan Rare Disease Centre, Department of Neurology, Huashan Hospital of Fudan University, Shanghai, China.

The findings were published online in JAMA Neurology.
 

Unmet Need

A rare chronic disease, myasthenia gravis is caused by autoantibodies that disrupt the neuromuscular junction, most commonly against the nicotinic acetylcholine receptor (AChR). This can cause a variety of symptoms, including difficulty swallowing, chewing, and talking, as well as severe, sometimes life-threatening, muscle weakness.

The estimated global prevalence of myasthenia gravis is 15-25 per 100,000, with cases doubling in the past 20 years.

Treatment for myasthenia gravis typically includes immune-suppressing drugs. But research suggests almost half of patients with generalized myasthenia gravis don’t achieve an adequate response or are intolerant to these treatments, and some therapies are costly or not readily accessible.

“Our treatment goal has evolved from saving patients to improving their quality of life, so we still need to explore safer and more effective novel treatment methods,” Dr. Zhao said.

Batoclimab is a fully humanized monoclonal IgG antibody that binds to FcRn and accelerates clearance of harmful IgG. A phase 2 trial provided preliminary evidence to support the efficacy of this agent in Chinese patients with generalized myasthenia gravis.

The current double-blind phase 3 trial included 132 adult patients (mean age, 44 years; 67% female) of Chinese Han ethnicity with generalized myasthenia gravis at 27 centers in China. Participants had a mean Myasthenia Gravis Activities of Daily Living (MG-ADL) score of 8.4 at baseline, and all but one was positive for AChR or muscle-specific kinase (MuSK) antibodies.

The treatment group received weekly subcutaneous injections of batoclimab at 680 mg for 6 weeks, followed by 4 weeks of observation. The control group received a placebo with the same treatment and follow-up schedule.

All patients received standard of care in addition to the assigned treatment, but changes in dosage and/or dosing frequency were not permitted. Patients received a second cycle if they still required treatment.
 

Bests Placebo

Overall, 90% of participants completed all six doses in cycle 1. The second treatment cycle was conducted in 115 patients, with 88% completing all six doses.

Patients were evaluated at baseline and then weekly for MG-ADL, Quantitative Myasthenia Gravis (QMG), Myasthenia Gravis Composite, and the 15-item revised version of the Myasthenia Gravis Quality of Life.

Sustained MG-ADL improvement — the primary outcome — was significantly higher in the batoclimab group compared with placebo (58% vs 31%, respectively; odds ratio, 3.45; P = .001).

While the rate of sustained MG-ADL improvement with batoclimab was lower than that reported for efgartigimod (68%) in a previous trial, that was primarily because of the more stringent definition of sustained MG-ADL improvement (three-point reduction vs two-point reduction from baseline), investigators said.

In the current trial, batoclimab had a rapid onset of action, with scores diverging between the treatment and placebo groups as early as the second week of therapy.

In the second treatment cycle, batoclimab once again outperformed placebo in sustained MG-ADL improvement (63% vs 36%, respectively; P = .002).

Batoclimab also bested placebo on secondary outcomes, including sustained QMG improvement (64% vs 41%; P = .008) and percent of patients achieving minimal symptom expression (25% vs 5%; P = .004).

Results of all subgroup analyses, including by age groups, sex, body weight, body mass index, and MG Foundation of America clinical classification, were consistent with those of the main analysis. The efficacy of batoclimab was also supported by all sensitivity analyses, underscoring the robustness of results.

Batoclimab led to a rapid and sustained reduction in serum AChR antibody levels, with a median reduction of 81% at week 6.
 

Well Tolerated

On discontinuation of batoclimab, serum total IgG returned to a level comparable with the baseline after 4 weeks. Reversibility of the drug’s effect is important considering the risk for infection from prolonged immune suppression, the authors noted.

The rate of peripheral edema was significantly higher in the treatment than in the placebo groups (39% vs 5%), but all cases were mild or moderate and deemed not clinically significant. The treatment group also had higher rates of upper respiratory tract infections (36% vs 22%) and of urinary tract infections (19% vs 15%).

“Although the incidence of upper respiratory tract and urinary tract infections was higher in the batoclimab group numerically, these were mild infections that did not require special treatment, so this is not a concern,” said Dr. Zhao.

Plasma albumin levels in the batoclimab group decreased significantly throughout the treatment cycle, starting at week 1 and reaching a decline of up to 31% at week 6. These levels increased rapidly toward baseline after treatment discontinuation.

High cholesterol levels were noted in the batoclimab group, plateauing by week 6. But levels returned to near baseline levels within 4 weeks after the final dose, and there were no serious related adverse reactions.

The rate of headache was slightly higher in the treatment group (6% vs 5% for placebo). “This finding may seem minor but could potentially translate into improved adherence in daily practice settings,” the authors wrote.

In previous studies, the efficacy of FcRn inhibitors in the Asian population was only examined in subgroup analyses with limited subjects. Finding an effective FcRn antagonist for China and surrounding regions is particularly important “considering the high mortality rate in hospitalized generalized myasthenia gravis patients in China,” the researchers noted.

The trial included only two treatment cycles, although results of an open-label extension trial examining longer-term efficacy of batoclimab should be available by the end of this year, said Dr. Zhao.

The trial was also not designed to investigate long-term safety, particularly infections and cardiovascular events. Only one study subject was negative for AChR or MuSK antibodies, which prevented researchers from assessing the drug’s efficacy in this subpopulation.
 

Questions Remain

Commenting on the study, Fredrik Piehl, MD, PhD, professor of neurology, Karolinska Institute, Stockholm, Sweden , said that recent studies of the two other FcRn antagonists were short-term and had limited long-term data. “We don’t know how valuable they may be for continued treatment,” Dr. Piehl said.

It’s also unclear how this new treatment modality compares with existing and emerging drug strategies in terms of the long-term benefit-risk balance, he added.

The rate of adverse events with batoclimab was high compared with placebo in this study and higher than in earlier studies of efgartigimod, Dr. Piehl noted.

“In this study, almost twice as many reported adverse events in the active arm compared with controls, while these differences tended to be smaller in previously reported trials,” he said.

The trial was funded by Nona Biosciences (Suzhou). Dr. Zhao reported being a full-time employee of Nona Biosciences (Suzhou), a subsidiary of Harbour BioMed Inc. He also reported receiving advisory board/consultant fees from Nona Biosciences, Roche, Sanofi, and Zailab outside the submitted work. Dr. Piehl has received research grants from Janssen, Merck KGaA, and UCB; and fees for serving on DMC in clinical trials with Chugai, Lundbeck, and Roche; and preparation of expert witness statement for Novartis.

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

Treatment with the investigational monoclonal antibody drug batoclimab significantly improved symptoms in patients with antibody-positive generalized myasthenia gravis, data from a new phase 3 study showed.

After 6 weeks of treatment, patients reported nearly 60% sustained improvement in daily activities and a rapid onset of action from batoclimab, a neonatal crystallizable fragment receptor (FcRn) antagonist.

The clinical effects and the extent of immunoglobulin G (IgG) reduction in this study were similar to those previously reported for efgartigimod and rozanolixizumab, two other FcRn antagonists, the investigators noted, adding that larger studies are needed to better understand the safety profile of batoclimab.

“While most generalized myasthenia gravis patients can achieve good disease control through conventional immunotherapy, there are still unmet needs with this disease,” said study investigator Chongbo Zhao, MD, National Center for Neurological Disorders, Huashan Rare Disease Centre, Department of Neurology, Huashan Hospital of Fudan University, Shanghai, China.

The findings were published online in JAMA Neurology.
 

Unmet Need

A rare chronic disease, myasthenia gravis is caused by autoantibodies that disrupt the neuromuscular junction, most commonly against the nicotinic acetylcholine receptor (AChR). This can cause a variety of symptoms, including difficulty swallowing, chewing, and talking, as well as severe, sometimes life-threatening, muscle weakness.

The estimated global prevalence of myasthenia gravis is 15-25 per 100,000, with cases doubling in the past 20 years.

Treatment for myasthenia gravis typically includes immune-suppressing drugs. But research suggests almost half of patients with generalized myasthenia gravis don’t achieve an adequate response or are intolerant to these treatments, and some therapies are costly or not readily accessible.

“Our treatment goal has evolved from saving patients to improving their quality of life, so we still need to explore safer and more effective novel treatment methods,” Dr. Zhao said.

Batoclimab is a fully humanized monoclonal IgG antibody that binds to FcRn and accelerates clearance of harmful IgG. A phase 2 trial provided preliminary evidence to support the efficacy of this agent in Chinese patients with generalized myasthenia gravis.

The current double-blind phase 3 trial included 132 adult patients (mean age, 44 years; 67% female) of Chinese Han ethnicity with generalized myasthenia gravis at 27 centers in China. Participants had a mean Myasthenia Gravis Activities of Daily Living (MG-ADL) score of 8.4 at baseline, and all but one was positive for AChR or muscle-specific kinase (MuSK) antibodies.

The treatment group received weekly subcutaneous injections of batoclimab at 680 mg for 6 weeks, followed by 4 weeks of observation. The control group received a placebo with the same treatment and follow-up schedule.

All patients received standard of care in addition to the assigned treatment, but changes in dosage and/or dosing frequency were not permitted. Patients received a second cycle if they still required treatment.
 

Bests Placebo

Overall, 90% of participants completed all six doses in cycle 1. The second treatment cycle was conducted in 115 patients, with 88% completing all six doses.

Patients were evaluated at baseline and then weekly for MG-ADL, Quantitative Myasthenia Gravis (QMG), Myasthenia Gravis Composite, and the 15-item revised version of the Myasthenia Gravis Quality of Life.

Sustained MG-ADL improvement — the primary outcome — was significantly higher in the batoclimab group compared with placebo (58% vs 31%, respectively; odds ratio, 3.45; P = .001).

While the rate of sustained MG-ADL improvement with batoclimab was lower than that reported for efgartigimod (68%) in a previous trial, that was primarily because of the more stringent definition of sustained MG-ADL improvement (three-point reduction vs two-point reduction from baseline), investigators said.

In the current trial, batoclimab had a rapid onset of action, with scores diverging between the treatment and placebo groups as early as the second week of therapy.

In the second treatment cycle, batoclimab once again outperformed placebo in sustained MG-ADL improvement (63% vs 36%, respectively; P = .002).

Batoclimab also bested placebo on secondary outcomes, including sustained QMG improvement (64% vs 41%; P = .008) and percent of patients achieving minimal symptom expression (25% vs 5%; P = .004).

Results of all subgroup analyses, including by age groups, sex, body weight, body mass index, and MG Foundation of America clinical classification, were consistent with those of the main analysis. The efficacy of batoclimab was also supported by all sensitivity analyses, underscoring the robustness of results.

Batoclimab led to a rapid and sustained reduction in serum AChR antibody levels, with a median reduction of 81% at week 6.
 

Well Tolerated

On discontinuation of batoclimab, serum total IgG returned to a level comparable with the baseline after 4 weeks. Reversibility of the drug’s effect is important considering the risk for infection from prolonged immune suppression, the authors noted.

The rate of peripheral edema was significantly higher in the treatment than in the placebo groups (39% vs 5%), but all cases were mild or moderate and deemed not clinically significant. The treatment group also had higher rates of upper respiratory tract infections (36% vs 22%) and of urinary tract infections (19% vs 15%).

“Although the incidence of upper respiratory tract and urinary tract infections was higher in the batoclimab group numerically, these were mild infections that did not require special treatment, so this is not a concern,” said Dr. Zhao.

Plasma albumin levels in the batoclimab group decreased significantly throughout the treatment cycle, starting at week 1 and reaching a decline of up to 31% at week 6. These levels increased rapidly toward baseline after treatment discontinuation.

High cholesterol levels were noted in the batoclimab group, plateauing by week 6. But levels returned to near baseline levels within 4 weeks after the final dose, and there were no serious related adverse reactions.

The rate of headache was slightly higher in the treatment group (6% vs 5% for placebo). “This finding may seem minor but could potentially translate into improved adherence in daily practice settings,” the authors wrote.

In previous studies, the efficacy of FcRn inhibitors in the Asian population was only examined in subgroup analyses with limited subjects. Finding an effective FcRn antagonist for China and surrounding regions is particularly important “considering the high mortality rate in hospitalized generalized myasthenia gravis patients in China,” the researchers noted.

The trial included only two treatment cycles, although results of an open-label extension trial examining longer-term efficacy of batoclimab should be available by the end of this year, said Dr. Zhao.

The trial was also not designed to investigate long-term safety, particularly infections and cardiovascular events. Only one study subject was negative for AChR or MuSK antibodies, which prevented researchers from assessing the drug’s efficacy in this subpopulation.
 

Questions Remain

Commenting on the study, Fredrik Piehl, MD, PhD, professor of neurology, Karolinska Institute, Stockholm, Sweden , said that recent studies of the two other FcRn antagonists were short-term and had limited long-term data. “We don’t know how valuable they may be for continued treatment,” Dr. Piehl said.

It’s also unclear how this new treatment modality compares with existing and emerging drug strategies in terms of the long-term benefit-risk balance, he added.

The rate of adverse events with batoclimab was high compared with placebo in this study and higher than in earlier studies of efgartigimod, Dr. Piehl noted.

“In this study, almost twice as many reported adverse events in the active arm compared with controls, while these differences tended to be smaller in previously reported trials,” he said.

The trial was funded by Nona Biosciences (Suzhou). Dr. Zhao reported being a full-time employee of Nona Biosciences (Suzhou), a subsidiary of Harbour BioMed Inc. He also reported receiving advisory board/consultant fees from Nona Biosciences, Roche, Sanofi, and Zailab outside the submitted work. Dr. Piehl has received research grants from Janssen, Merck KGaA, and UCB; and fees for serving on DMC in clinical trials with Chugai, Lundbeck, and Roche; and preparation of expert witness statement for Novartis.

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

TOPLINE:

Patients with multiple sclerosis (MS) have almost double the risk for seizures, with the risk even greater with sphingosine-1-phosphate receptor (S1PR) modulators, results of a new meta-analysis of randomized controlled trials (RCTs) suggest. Those with a progressive disease phenotype are at particularly high seizure risk.

METHODOLOGY:

• The meta-analysis included 63 phase 3 RCTs with 53,535 patients.
• Most of the studies included in the meta-analysis investigated disease-modifying treatments compared with placebo or an active comparator such as interferon beta, teriflunomide, and dimethyl fumarate, in terms of relapse rate and/or disability progression.
• Researchers extracted relevant information from studies, including MS subtype (clinically isolated syndrome, relapsing-remitting, primary progressive, or secondary progressive MS), mean Expanded Disability Status Scale (EDSS) score, lesion volume on T2-hyperintense sequence, normalized brain volume, and number of seizures or epilepsy events.
• They calculated the pooled effect size of studies on the incidence rate of seizure or epilepsy as the number of events per patient-years and explored which variables influenced the pooled effect size.

TAKEAWAY:

• A total of 120 patients experienced epileptic seizure events over a median follow-up of 2 years, resulting in a pooled incidence rate of 68.0 (95% CI, 49.1-86.9) per 100,000 patient-years, which investigators noted is significantly higher than the general population rate of 34.6.
• Higher seizure incidence rates were found among patients with progressive disease courses, longer time since clinical onset, higher EDSS scores, and lower normalized brain volume; age and T2 lesion volume did not affect the pooled effect size.
• Patients treated with S1PR modulators (fingolimod, ozanimod, ponesimod, and siponimod) had more than double the risk for seizure compared with placebo or comparators (estimated incident seizure risk ratio, 2.45; P = .008).

IN PRACTICE:

“Our findings underscore epilepsy as a significant comorbidity in MS and emphasize the necessity for further research into its triggers, preventive measures and treatment strategies,” the authors wrote.

SOURCE:

The study, led by Valeria Pozzilli, Unit of Neurology, Neurophysiology and Neurobiology, Department of Medicine and Surgery, Campus Bio-Medico University, Roma, Italy, was published online in the Journal of Neurology, Neurosurgery, and Psychiatry.

LIMITATIONS:

As none of the included RCTs considered epilepsy an exclusion criterion, patients with comorbid epilepsy may have been enrolled in these studies. There was significant diversity in reporting of adverse events across studies. While this study’s statistical methodology was robust, the findings can’t be applied directly to individuals due to the risk for ecological fallacy.

DISCLOSURES:

Pozzilli had no relevant conflicts of interests. See paper for disclosures of other authors.

A version of this article appeared on Medscape.com.

TOPLINE:

Patients with multiple sclerosis (MS) have almost double the risk for seizures, with the risk even greater with sphingosine-1-phosphate receptor (S1PR) modulators, results of a new meta-analysis of randomized controlled trials (RCTs) suggest. Those with a progressive disease phenotype are at particularly high seizure risk.

METHODOLOGY:

• The meta-analysis included 63 phase 3 RCTs with 53,535 patients.
• Most of the studies included in the meta-analysis investigated disease-modifying treatments compared with placebo or an active comparator such as interferon beta, teriflunomide, and dimethyl fumarate, in terms of relapse rate and/or disability progression.
• Researchers extracted relevant information from studies, including MS subtype (clinically isolated syndrome, relapsing-remitting, primary progressive, or secondary progressive MS), mean Expanded Disability Status Scale (EDSS) score, lesion volume on T2-hyperintense sequence, normalized brain volume, and number of seizures or epilepsy events.
• They calculated the pooled effect size of studies on the incidence rate of seizure or epilepsy as the number of events per patient-years and explored which variables influenced the pooled effect size.

TAKEAWAY:

• A total of 120 patients experienced epileptic seizure events over a median follow-up of 2 years, resulting in a pooled incidence rate of 68.0 (95% CI, 49.1-86.9) per 100,000 patient-years, which investigators noted is significantly higher than the general population rate of 34.6.
• Higher seizure incidence rates were found among patients with progressive disease courses, longer time since clinical onset, higher EDSS scores, and lower normalized brain volume; age and T2 lesion volume did not affect the pooled effect size.
• Patients treated with S1PR modulators (fingolimod, ozanimod, ponesimod, and siponimod) had more than double the risk for seizure compared with placebo or comparators (estimated incident seizure risk ratio, 2.45; P = .008).

IN PRACTICE:

“Our findings underscore epilepsy as a significant comorbidity in MS and emphasize the necessity for further research into its triggers, preventive measures and treatment strategies,” the authors wrote.

SOURCE:

The study, led by Valeria Pozzilli, Unit of Neurology, Neurophysiology and Neurobiology, Department of Medicine and Surgery, Campus Bio-Medico University, Roma, Italy, was published online in the Journal of Neurology, Neurosurgery, and Psychiatry.

LIMITATIONS:

As none of the included RCTs considered epilepsy an exclusion criterion, patients with comorbid epilepsy may have been enrolled in these studies. There was significant diversity in reporting of adverse events across studies. While this study’s statistical methodology was robust, the findings can’t be applied directly to individuals due to the risk for ecological fallacy.

DISCLOSURES:

Pozzilli had no relevant conflicts of interests. See paper for disclosures of other authors.

A version of this article appeared on Medscape.com.

TOPLINE:

Patients with multiple sclerosis (MS) have almost double the risk for seizures, with the risk even greater with sphingosine-1-phosphate receptor (S1PR) modulators, results of a new meta-analysis of randomized controlled trials (RCTs) suggest. Those with a progressive disease phenotype are at particularly high seizure risk.

METHODOLOGY:

• The meta-analysis included 63 phase 3 RCTs with 53,535 patients.
• Most of the studies included in the meta-analysis investigated disease-modifying treatments compared with placebo or an active comparator such as interferon beta, teriflunomide, and dimethyl fumarate, in terms of relapse rate and/or disability progression.
• Researchers extracted relevant information from studies, including MS subtype (clinically isolated syndrome, relapsing-remitting, primary progressive, or secondary progressive MS), mean Expanded Disability Status Scale (EDSS) score, lesion volume on T2-hyperintense sequence, normalized brain volume, and number of seizures or epilepsy events.
• They calculated the pooled effect size of studies on the incidence rate of seizure or epilepsy as the number of events per patient-years and explored which variables influenced the pooled effect size.

TAKEAWAY:

• A total of 120 patients experienced epileptic seizure events over a median follow-up of 2 years, resulting in a pooled incidence rate of 68.0 (95% CI, 49.1-86.9) per 100,000 patient-years, which investigators noted is significantly higher than the general population rate of 34.6.
• Higher seizure incidence rates were found among patients with progressive disease courses, longer time since clinical onset, higher EDSS scores, and lower normalized brain volume; age and T2 lesion volume did not affect the pooled effect size.
• Patients treated with S1PR modulators (fingolimod, ozanimod, ponesimod, and siponimod) had more than double the risk for seizure compared with placebo or comparators (estimated incident seizure risk ratio, 2.45; P = .008).

IN PRACTICE:

“Our findings underscore epilepsy as a significant comorbidity in MS and emphasize the necessity for further research into its triggers, preventive measures and treatment strategies,” the authors wrote.

SOURCE:

The study, led by Valeria Pozzilli, Unit of Neurology, Neurophysiology and Neurobiology, Department of Medicine and Surgery, Campus Bio-Medico University, Roma, Italy, was published online in the Journal of Neurology, Neurosurgery, and Psychiatry.

LIMITATIONS:

As none of the included RCTs considered epilepsy an exclusion criterion, patients with comorbid epilepsy may have been enrolled in these studies. There was significant diversity in reporting of adverse events across studies. While this study’s statistical methodology was robust, the findings can’t be applied directly to individuals due to the risk for ecological fallacy.

DISCLOSURES:

Pozzilli had no relevant conflicts of interests. See paper for disclosures of other authors.

A version of this article appeared on Medscape.com.

Posttraumatic headache (PTH) is associated with an increase in iron accumulation in certain brain regions , notably those involved in the pain network, early research shows.

Investigators found positive correlations between iron accumulation and headache frequency, number of lifetime mild traumatic brain injuries (mTBIs), and time since last mTBI.

The findings come on the heels of previous research showing patients with iron accumulation in certain brain regions don’t respond as well to treatment, study investigator, Simona Nikolova, PhD, assistant professor of neurology, Mayo Clinic, Phoenix, Arizona, told this news organization.

“This is really important, and doctors need to be aware of it. If you have a patient who is not responding to treatment, then you know what to look at,” she said. 

The findings (Abstract #3379) will be presented on April 15 at the American Academy of Neurology (AAN) 2024 Annual Meeting. 
 

Dose Effect

The study included 60 people with acute PTH due to mTBI. Most were White, and almost half had sustained a concussion due to a fall, with about 30% injured in a vehicle accident and a smaller number injured during a fight.

The mean number of lifetime mTBIs was 2.4, although participants had sustained as many as five or six and as few as one. The mean time from the most recent mTBI was 25 days, and the mean score on the Sport Concussion Assessment Tool (SCAT), which measures postconcussion symptom severity, was 29.

Most in the mTBI group (43) had migraine or probable migraine, and 14 had tension-type headaches. Mean headache frequency was 81%.

Researchers matched these patients with 60 controls without concussion or headache. Because iron accumulation is age-related, they tried to eliminate this covariant by pairing each participant with mTBI with an age- and sex-matched control.

All participants underwent a type of brain MRI known as T2* weighted sequence that can identify brain iron accumulation, a marker of neural injury. 

Investigators found that the PTH group had significantly higher levels of iron accumulation in several areas of the brain, most of which are part of a “pain network” that includes about 63 areas of the brain, Dr. Nikolova said.

The study wasn’t designed to determine how much more iron accumulation mTBI patients had vs controls. 

“We can’t say it was twice as much or three times as much; we can only say it was significant. Measuring concentrations in PTH patients and comparing that with controls is something we haven’t don’t yet,” said Dr. Nikolova.

Areas of the brain with increased iron accumulation, included the periaqueductal gray (PAG), anterior cingulated cortex, and supramarginal gyrus. 

Research suggests patients with migraine who have elevated levels of iron in the PAG have a poorer response to botulinum toxin treatment. An earlier study by the same team showed a poorer response to the calcitonin gene-related peptide inhibitor erenumab in migraine patients with elevated iron in the PAG.

Researchers discovered that those with more lifetime TBIs had higher iron accumulation in the right gyrus rectus and right putamen vs those with fewer injuries and that headache frequency was associated with iron accumulation in the posterior corona radiata, bilateral temporal, right frontal, bilateral supplemental motor area, left fusiform, right hippocampus, sagittal striatum, and left cerebellum.
 

Surprising Result

The investigators also found a link between time since the most recent mTBI and iron accumulation in the bilateral temporal, right hippocampus, posterior and superior corona radiata, bilateral thalamus, right precuneus and cuneus, right lingual, and right cerebellum. 

“The more time that passed since the concussion occurred, the more likely that people had higher iron levels,” said Dr. Nikolova.

It’s perhaps to be expected that the length of time since injury is linked to iron accumulation in the brain as iron accumulates over time. But even those whose injury was relatively recent had higher amounts of iron, which Dr. Nikolova said was “surprising.”

“We thought iron accumulates over time so we were thinking maybe we should be doing a longitudinal study to see what happens, but we see definite iron accumulation due to injury shortly after the injury,” she said.

There was no association between iron accumulation and symptom severity as measured by SCAT scores.
 

Questions Remain

It’s unclear why iron accumulates after an injury or what the ramifications are of this accumulation, Dr. Nikolova noted. 

The imaging used in the study doesn’t distinguish between “bound” iron found after a hemorrhage and “free” iron in the brain. The free iron type has been shown to be increased after TBI and is “the stuff you should be afraid of,” Dr. Nikolova said.

Iron’s role in the metabolic process is important, but must be closely regulated, she said. Even a small accumulation can lead to oxidative stress.

Researchers are investigating whether the findings would be similar in mTBI but no headache and want to increase the number of study participants. A larger, more diverse sample would allow them to probe other questions, including whether iron accumulation is different in men and women. More data could also eventually lead to iron accumulation becoming a biomarker for concussion and PTH, Dr. Nikolova said.

“If you know a certain person has that biomarker, you might be able to administer a drug or some therapeutic procedure to prevent that iron from continuing to accumulate in the brain.”

Chelation drugs and other therapies may clear iron from the body but not necessarily from the brain. 

Commenting on the study for this news organization, Frank Conidi, MD, director, Florida Center for Headache and Sports Neurology, Port St. Lucie , said that the study supports the hypothesis that concussion “is not a benign process for the brain, and the cumulative effect of repetitive head injury can result in permanent brain injury.”

He said that he found the accumulation of iron in cortical structures particularly interesting. This, he said, differs from most current research that suggests head trauma mainly results in damage to white matter tracts.

He prefers the term “concussion” over “mild traumatic brain injury” which was used in the study. “Recent guidelines, including some that I’ve been involved with, have defined mild traumatic brain injury as a more permanent process,” he said.

The study was supported by the US Department of Defense and National Institutes of Health. No relevant conflicts of interest were disclosed. 

A version of this article appeared on Medscape.com.

Posttraumatic headache (PTH) is associated with an increase in iron accumulation in certain brain regions , notably those involved in the pain network, early research shows.

Investigators found positive correlations between iron accumulation and headache frequency, number of lifetime mild traumatic brain injuries (mTBIs), and time since last mTBI.

The findings come on the heels of previous research showing patients with iron accumulation in certain brain regions don’t respond as well to treatment, study investigator, Simona Nikolova, PhD, assistant professor of neurology, Mayo Clinic, Phoenix, Arizona, told this news organization.

“This is really important, and doctors need to be aware of it. If you have a patient who is not responding to treatment, then you know what to look at,” she said. 

The findings (Abstract #3379) will be presented on April 15 at the American Academy of Neurology (AAN) 2024 Annual Meeting. 
 

Dose Effect

The study included 60 people with acute PTH due to mTBI. Most were White, and almost half had sustained a concussion due to a fall, with about 30% injured in a vehicle accident and a smaller number injured during a fight.

The mean number of lifetime mTBIs was 2.4, although participants had sustained as many as five or six and as few as one. The mean time from the most recent mTBI was 25 days, and the mean score on the Sport Concussion Assessment Tool (SCAT), which measures postconcussion symptom severity, was 29.

Most in the mTBI group (43) had migraine or probable migraine, and 14 had tension-type headaches. Mean headache frequency was 81%.

Researchers matched these patients with 60 controls without concussion or headache. Because iron accumulation is age-related, they tried to eliminate this covariant by pairing each participant with mTBI with an age- and sex-matched control.

All participants underwent a type of brain MRI known as T2* weighted sequence that can identify brain iron accumulation, a marker of neural injury. 

Investigators found that the PTH group had significantly higher levels of iron accumulation in several areas of the brain, most of which are part of a “pain network” that includes about 63 areas of the brain, Dr. Nikolova said.

The study wasn’t designed to determine how much more iron accumulation mTBI patients had vs controls. 

“We can’t say it was twice as much or three times as much; we can only say it was significant. Measuring concentrations in PTH patients and comparing that with controls is something we haven’t don’t yet,” said Dr. Nikolova.

Areas of the brain with increased iron accumulation, included the periaqueductal gray (PAG), anterior cingulated cortex, and supramarginal gyrus. 

Research suggests patients with migraine who have elevated levels of iron in the PAG have a poorer response to botulinum toxin treatment. An earlier study by the same team showed a poorer response to the calcitonin gene-related peptide inhibitor erenumab in migraine patients with elevated iron in the PAG.

Researchers discovered that those with more lifetime TBIs had higher iron accumulation in the right gyrus rectus and right putamen vs those with fewer injuries and that headache frequency was associated with iron accumulation in the posterior corona radiata, bilateral temporal, right frontal, bilateral supplemental motor area, left fusiform, right hippocampus, sagittal striatum, and left cerebellum.
 

Surprising Result

The investigators also found a link between time since the most recent mTBI and iron accumulation in the bilateral temporal, right hippocampus, posterior and superior corona radiata, bilateral thalamus, right precuneus and cuneus, right lingual, and right cerebellum. 

“The more time that passed since the concussion occurred, the more likely that people had higher iron levels,” said Dr. Nikolova.

It’s perhaps to be expected that the length of time since injury is linked to iron accumulation in the brain as iron accumulates over time. But even those whose injury was relatively recent had higher amounts of iron, which Dr. Nikolova said was “surprising.”

“We thought iron accumulates over time so we were thinking maybe we should be doing a longitudinal study to see what happens, but we see definite iron accumulation due to injury shortly after the injury,” she said.

There was no association between iron accumulation and symptom severity as measured by SCAT scores.
 

Questions Remain

It’s unclear why iron accumulates after an injury or what the ramifications are of this accumulation, Dr. Nikolova noted. 

The imaging used in the study doesn’t distinguish between “bound” iron found after a hemorrhage and “free” iron in the brain. The free iron type has been shown to be increased after TBI and is “the stuff you should be afraid of,” Dr. Nikolova said.

Iron’s role in the metabolic process is important, but must be closely regulated, she said. Even a small accumulation can lead to oxidative stress.

Researchers are investigating whether the findings would be similar in mTBI but no headache and want to increase the number of study participants. A larger, more diverse sample would allow them to probe other questions, including whether iron accumulation is different in men and women. More data could also eventually lead to iron accumulation becoming a biomarker for concussion and PTH, Dr. Nikolova said.

“If you know a certain person has that biomarker, you might be able to administer a drug or some therapeutic procedure to prevent that iron from continuing to accumulate in the brain.”

Chelation drugs and other therapies may clear iron from the body but not necessarily from the brain. 

Commenting on the study for this news organization, Frank Conidi, MD, director, Florida Center for Headache and Sports Neurology, Port St. Lucie , said that the study supports the hypothesis that concussion “is not a benign process for the brain, and the cumulative effect of repetitive head injury can result in permanent brain injury.”

He said that he found the accumulation of iron in cortical structures particularly interesting. This, he said, differs from most current research that suggests head trauma mainly results in damage to white matter tracts.

He prefers the term “concussion” over “mild traumatic brain injury” which was used in the study. “Recent guidelines, including some that I’ve been involved with, have defined mild traumatic brain injury as a more permanent process,” he said.

The study was supported by the US Department of Defense and National Institutes of Health. No relevant conflicts of interest were disclosed. 

A version of this article appeared on Medscape.com.

Posttraumatic headache (PTH) is associated with an increase in iron accumulation in certain brain regions , notably those involved in the pain network, early research shows.

Investigators found positive correlations between iron accumulation and headache frequency, number of lifetime mild traumatic brain injuries (mTBIs), and time since last mTBI.

The findings come on the heels of previous research showing patients with iron accumulation in certain brain regions don’t respond as well to treatment, study investigator, Simona Nikolova, PhD, assistant professor of neurology, Mayo Clinic, Phoenix, Arizona, told this news organization.

“This is really important, and doctors need to be aware of it. If you have a patient who is not responding to treatment, then you know what to look at,” she said. 

The findings (Abstract #3379) will be presented on April 15 at the American Academy of Neurology (AAN) 2024 Annual Meeting. 
 

Dose Effect

The study included 60 people with acute PTH due to mTBI. Most were White, and almost half had sustained a concussion due to a fall, with about 30% injured in a vehicle accident and a smaller number injured during a fight.

The mean number of lifetime mTBIs was 2.4, although participants had sustained as many as five or six and as few as one. The mean time from the most recent mTBI was 25 days, and the mean score on the Sport Concussion Assessment Tool (SCAT), which measures postconcussion symptom severity, was 29.

Most in the mTBI group (43) had migraine or probable migraine, and 14 had tension-type headaches. Mean headache frequency was 81%.

Researchers matched these patients with 60 controls without concussion or headache. Because iron accumulation is age-related, they tried to eliminate this covariant by pairing each participant with mTBI with an age- and sex-matched control.

All participants underwent a type of brain MRI known as T2* weighted sequence that can identify brain iron accumulation, a marker of neural injury. 

Investigators found that the PTH group had significantly higher levels of iron accumulation in several areas of the brain, most of which are part of a “pain network” that includes about 63 areas of the brain, Dr. Nikolova said.

The study wasn’t designed to determine how much more iron accumulation mTBI patients had vs controls. 

“We can’t say it was twice as much or three times as much; we can only say it was significant. Measuring concentrations in PTH patients and comparing that with controls is something we haven’t don’t yet,” said Dr. Nikolova.

Areas of the brain with increased iron accumulation, included the periaqueductal gray (PAG), anterior cingulated cortex, and supramarginal gyrus. 

Research suggests patients with migraine who have elevated levels of iron in the PAG have a poorer response to botulinum toxin treatment. An earlier study by the same team showed a poorer response to the calcitonin gene-related peptide inhibitor erenumab in migraine patients with elevated iron in the PAG.

Researchers discovered that those with more lifetime TBIs had higher iron accumulation in the right gyrus rectus and right putamen vs those with fewer injuries and that headache frequency was associated with iron accumulation in the posterior corona radiata, bilateral temporal, right frontal, bilateral supplemental motor area, left fusiform, right hippocampus, sagittal striatum, and left cerebellum.
 

Surprising Result

The investigators also found a link between time since the most recent mTBI and iron accumulation in the bilateral temporal, right hippocampus, posterior and superior corona radiata, bilateral thalamus, right precuneus and cuneus, right lingual, and right cerebellum. 

“The more time that passed since the concussion occurred, the more likely that people had higher iron levels,” said Dr. Nikolova.

It’s perhaps to be expected that the length of time since injury is linked to iron accumulation in the brain as iron accumulates over time. But even those whose injury was relatively recent had higher amounts of iron, which Dr. Nikolova said was “surprising.”

“We thought iron accumulates over time so we were thinking maybe we should be doing a longitudinal study to see what happens, but we see definite iron accumulation due to injury shortly after the injury,” she said.

There was no association between iron accumulation and symptom severity as measured by SCAT scores.
 

Questions Remain

It’s unclear why iron accumulates after an injury or what the ramifications are of this accumulation, Dr. Nikolova noted. 

The imaging used in the study doesn’t distinguish between “bound” iron found after a hemorrhage and “free” iron in the brain. The free iron type has been shown to be increased after TBI and is “the stuff you should be afraid of,” Dr. Nikolova said.

Iron’s role in the metabolic process is important, but must be closely regulated, she said. Even a small accumulation can lead to oxidative stress.

Researchers are investigating whether the findings would be similar in mTBI but no headache and want to increase the number of study participants. A larger, more diverse sample would allow them to probe other questions, including whether iron accumulation is different in men and women. More data could also eventually lead to iron accumulation becoming a biomarker for concussion and PTH, Dr. Nikolova said.

“If you know a certain person has that biomarker, you might be able to administer a drug or some therapeutic procedure to prevent that iron from continuing to accumulate in the brain.”

Chelation drugs and other therapies may clear iron from the body but not necessarily from the brain. 

Commenting on the study for this news organization, Frank Conidi, MD, director, Florida Center for Headache and Sports Neurology, Port St. Lucie , said that the study supports the hypothesis that concussion “is not a benign process for the brain, and the cumulative effect of repetitive head injury can result in permanent brain injury.”

He said that he found the accumulation of iron in cortical structures particularly interesting. This, he said, differs from most current research that suggests head trauma mainly results in damage to white matter tracts.

He prefers the term “concussion” over “mild traumatic brain injury” which was used in the study. “Recent guidelines, including some that I’ve been involved with, have defined mild traumatic brain injury as a more permanent process,” he said.

The study was supported by the US Department of Defense and National Institutes of Health. No relevant conflicts of interest were disclosed. 

A version of this article appeared on Medscape.com.

TOPLINE:

A history of herpes simplex virus (HSV) is associated with a more than doubling of the risk for dementia in older people, results of a prospective epidemiological study showed. 

METHODOLOGY:

• The study included 1002 dementia-free 70-year-olds from the Prospective Investigation of Vasculature in Uppsala Seniors cohort who were assessed at baseline and at age 75 and 80 years and followed through medical records at age 85 years.
• Researchers collected and analyzed blood samples to detect anti-HSV and anti-HSV-1 immunoglobulin (Ig) G, anti-cytomegalovirus (CMV) IgG, anti-HSV IgM, and anti-HSV and anti-CMV IgG levels and apolipoprotein epsilon 4 (APOE 4) status of participants.
• Investigators collected information on anti-herpesvirus drug treatment and reviewed dementia diagnoses obtained from medical records to classify as established or probable dementia or Alzheimer’s disease (AD).

TAKEAWAY: 

• 82% of participants were anti-HSV IgG carriers, of which 6% had received drug treatment for herpes virus, and 7% of participants developed all-cause dementia and 4% AD during the median 15-year follow up.
• In HSV and HSV-1 subsamples, treatment for herpes virus was not significantly associated with lower risks for AD (HR, 1.46, P = .532 and HR, 1.64; P = .419, respectively) or dementia (HR 1.70; P = .222 and HR, 1.60; P = .320, respectively).
• There was no significant interaction between anti-HSV IgG seroprevalence and APOE 4 with regard to dementia risk, likely due to underpowering, and there were no associations between anti-CMV IgG positivity or anti-HSV IgM positivity and AD or dementia.

IN PRACTICE:

“What’s special about this particular study is that the participants are roughly the same age, which makes the results even more reliable since age differences, which are otherwise linked to the development of dementia, cannot confuse the results,” lead author Erika Vestin, a medical student in the Department of Public Health and Caring Sciences, Clinical Geriatrics, Uppsala University, Sweden, said in a press release. Findings may drive dementia research further towards treating the illness at an early stage using common anti-herpes virus drugs, Ms. Vestin added.

SOURCE:

The study, with Ms. Vestin as lead author, was published online on February 14, 2024, in the Journal of Alzheimer’s Disease.

LIMITATIONS:

The study underrepresented people with diabetes, heart failure, and stroke and lacked information on treatment compliance, dosage, and length and number of prescriptions, which prevented analysis of dose dependency. Since dementia data collection relied on medical records, dementia cases may be underreported. Some cases of AD could have been misclassified as vascular dementia or other dementia. 

DISCLOSURES:

The study was supported by the Gun and Bertil Stohne’s Foundation, Swedish Dementia Association, Swedish Society of Medicine, Märta Lundqvist Foundation, Thureus Foundation, Region Uppsala, Gamla Tjänarinnor Foundation, and Swedish Brain Foundation. The authors had no relevant conflicts of interest.
 

A version of this article appeared on Medscape.com.

TOPLINE:

A history of herpes simplex virus (HSV) is associated with a more than doubling of the risk for dementia in older people, results of a prospective epidemiological study showed. 

METHODOLOGY:

• The study included 1002 dementia-free 70-year-olds from the Prospective Investigation of Vasculature in Uppsala Seniors cohort who were assessed at baseline and at age 75 and 80 years and followed through medical records at age 85 years.
• Researchers collected and analyzed blood samples to detect anti-HSV and anti-HSV-1 immunoglobulin (Ig) G, anti-cytomegalovirus (CMV) IgG, anti-HSV IgM, and anti-HSV and anti-CMV IgG levels and apolipoprotein epsilon 4 (APOE 4) status of participants.
• Investigators collected information on anti-herpesvirus drug treatment and reviewed dementia diagnoses obtained from medical records to classify as established or probable dementia or Alzheimer’s disease (AD).

TAKEAWAY: 

• 82% of participants were anti-HSV IgG carriers, of which 6% had received drug treatment for herpes virus, and 7% of participants developed all-cause dementia and 4% AD during the median 15-year follow up.
• In HSV and HSV-1 subsamples, treatment for herpes virus was not significantly associated with lower risks for AD (HR, 1.46, P = .532 and HR, 1.64; P = .419, respectively) or dementia (HR 1.70; P = .222 and HR, 1.60; P = .320, respectively).
• There was no significant interaction between anti-HSV IgG seroprevalence and APOE 4 with regard to dementia risk, likely due to underpowering, and there were no associations between anti-CMV IgG positivity or anti-HSV IgM positivity and AD or dementia.

IN PRACTICE:

“What’s special about this particular study is that the participants are roughly the same age, which makes the results even more reliable since age differences, which are otherwise linked to the development of dementia, cannot confuse the results,” lead author Erika Vestin, a medical student in the Department of Public Health and Caring Sciences, Clinical Geriatrics, Uppsala University, Sweden, said in a press release. Findings may drive dementia research further towards treating the illness at an early stage using common anti-herpes virus drugs, Ms. Vestin added.

SOURCE:

The study, with Ms. Vestin as lead author, was published online on February 14, 2024, in the Journal of Alzheimer’s Disease.

LIMITATIONS:

The study underrepresented people with diabetes, heart failure, and stroke and lacked information on treatment compliance, dosage, and length and number of prescriptions, which prevented analysis of dose dependency. Since dementia data collection relied on medical records, dementia cases may be underreported. Some cases of AD could have been misclassified as vascular dementia or other dementia. 

DISCLOSURES:

The study was supported by the Gun and Bertil Stohne’s Foundation, Swedish Dementia Association, Swedish Society of Medicine, Märta Lundqvist Foundation, Thureus Foundation, Region Uppsala, Gamla Tjänarinnor Foundation, and Swedish Brain Foundation. The authors had no relevant conflicts of interest.
 

A version of this article appeared on Medscape.com.

TOPLINE:

A history of herpes simplex virus (HSV) is associated with a more than doubling of the risk for dementia in older people, results of a prospective epidemiological study showed. 

METHODOLOGY:

• The study included 1002 dementia-free 70-year-olds from the Prospective Investigation of Vasculature in Uppsala Seniors cohort who were assessed at baseline and at age 75 and 80 years and followed through medical records at age 85 years.
• Researchers collected and analyzed blood samples to detect anti-HSV and anti-HSV-1 immunoglobulin (Ig) G, anti-cytomegalovirus (CMV) IgG, anti-HSV IgM, and anti-HSV and anti-CMV IgG levels and apolipoprotein epsilon 4 (APOE 4) status of participants.
• Investigators collected information on anti-herpesvirus drug treatment and reviewed dementia diagnoses obtained from medical records to classify as established or probable dementia or Alzheimer’s disease (AD).

TAKEAWAY: 

• 82% of participants were anti-HSV IgG carriers, of which 6% had received drug treatment for herpes virus, and 7% of participants developed all-cause dementia and 4% AD during the median 15-year follow up.
• In HSV and HSV-1 subsamples, treatment for herpes virus was not significantly associated with lower risks for AD (HR, 1.46, P = .532 and HR, 1.64; P = .419, respectively) or dementia (HR 1.70; P = .222 and HR, 1.60; P = .320, respectively).
• There was no significant interaction between anti-HSV IgG seroprevalence and APOE 4 with regard to dementia risk, likely due to underpowering, and there were no associations between anti-CMV IgG positivity or anti-HSV IgM positivity and AD or dementia.

IN PRACTICE:

“What’s special about this particular study is that the participants are roughly the same age, which makes the results even more reliable since age differences, which are otherwise linked to the development of dementia, cannot confuse the results,” lead author Erika Vestin, a medical student in the Department of Public Health and Caring Sciences, Clinical Geriatrics, Uppsala University, Sweden, said in a press release. Findings may drive dementia research further towards treating the illness at an early stage using common anti-herpes virus drugs, Ms. Vestin added.

SOURCE:

The study, with Ms. Vestin as lead author, was published online on February 14, 2024, in the Journal of Alzheimer’s Disease.

LIMITATIONS:

The study underrepresented people with diabetes, heart failure, and stroke and lacked information on treatment compliance, dosage, and length and number of prescriptions, which prevented analysis of dose dependency. Since dementia data collection relied on medical records, dementia cases may be underreported. Some cases of AD could have been misclassified as vascular dementia or other dementia. 

DISCLOSURES:

The study was supported by the Gun and Bertil Stohne’s Foundation, Swedish Dementia Association, Swedish Society of Medicine, Märta Lundqvist Foundation, Thureus Foundation, Region Uppsala, Gamla Tjänarinnor Foundation, and Swedish Brain Foundation. The authors had no relevant conflicts of interest.
 

A version of this article appeared on Medscape.com.

TOPLINE: 

Accelerometer-measured physical activity (PA), whether light, moderate, or vigorous, is associated with lower risk for heart failure (HF) in older women while more sedentary time is associated with higher HF risk in these women, results of a new study suggest. 

METHODOLOGY:

• The analysis included 5951 women aged 63-99 years (mean age, 78.6 years), including 33.7% Black, 17.2% Hispanic, and 49.2% White individuals without HF from the Objective Physical Activity and Cardiovascular Health (OPACH) study, an ancillary to the Women’s Health Initiative Long-Life Study.
• Participants wore an accelerometer on their hip 24 hours a day for up to 7 consecutive days except when in water, kept nightly sleep logs, completed questionnaires to provide information on medical history and sociodemographic and lifestyle factors, and self-rated their general health status.
• Researchers recorded their use of assistive walking devices; determined body mass index as well as blood pressure; obtained fasting serum glucose, total and high-density lipoprotein cholesterol, triglyceride, and high-sensitivity C-reactive protein concentrations; and scored participants’ multimorbidity.
• They determined intensity-specific PA using vector magnitude acceleration cut points (light PA, 19-518 counts/15 s; moderate to vigorous PA [MVPA], > 518) and steps per day using dedicated software, and they quantified sedentary time (total and mean bout duration).
• The primary outcome was overall self-reported HF later adjudicated by physicians using medical record reviews; secondary endpoints were heart failure with reduced ejection fraction (HFrEF) and preserved EF (HFpEF), classified by an EF of < 45% or 45% or > 45%, respectively, after cardiac imaging.

TAKEAWAY:

• A total of 407 HF cases (including 257 HFpEF and 110 HFrEF) were identified during a mean of 7.5 years of follow-up.
• HFrEF was not associated with PA measures in the fully adjusted model (which controlled extensively for health and physical functioning status), but overall HF and HFpEF were inversely associated with total PA (per 1-standard deviation [SD] increment: hazard ratio [HR] 0.85; 95% CI, 0.75-0.95 and HR, 0.78; 95% CI, 0.67-0.91, respectively), light PA (HR, 0.88; 95% CI, 0.78-0.98 and HR, 0.80; 95% CI, 0.70-0.93, respectively) and MVPA (HR, 0.84; 95% CI, 0.73-0.97 and HR, 0.85; 95% CI, 0.72-1.01, respectively).
• With regard to daily steps, each 1-SD increment was associated with a significant 26% lower risk for overall HF (HR 0.74; 95% CI, 0.63-0.88) and 29% lower risk for HFpEF (HR, 0.71; 95% CI, 0.57-0.88), with these inverse risks becoming significant at about 2000 steps/d, “far less than the often touted 10,000 steps/d for promoting health benefits,” noted the authors.
• Total sedentary time was positively associated (per 1 SD in the fully adjusted model) with risks of overall HF (HR, 1.17; 95% CI, 1.04-1.33) and HFpEF (HR, 1.29; 95% CI, 1.10-1.51) but not HFrEF; mean sedentary bout duration was significantly inversely associated with HFrEF (per 1 SD: HR, 0.76; 95% CI, 0.61-0.97), although the relatively small number of cases at the extremes of bout duration may contribute to this unexpected inverse association, said the authors.

IN PRACTICE:

The implications of promoting PA, regardless of intensity, for primary HFpEF prevention in later life, “has profound public health and clinical relevance,” the authors concluded. They noted that HFpEF is a “burgeoning epidemic” that disproportionately affects women and minorities with limited available therapies.

STUDY DETAILS:

The study, led by Michael J. LaMonte, PhD, MPH, University at Buffalo-SUNY, Buffalo, New York, was published online on February 21, 2024, in JAMA Cardiology.

LIMITATIONS:

There was only a single accelerometer assessment of PA and sedentary exposures and relatively small numbers of HFrEF cases, which restricted analytic precision. Although researchers controlled for several established vascular biomarkers, they did not have HF-specific measures such as cardiac troponin or N-terminal pro–brain natriuretic peptide. It’s unknown if the findings can be generalized to men and populations dissimilar to women in OPACH.

DISCLOSURES:

The study was funded in part by the National Heart, Lung, and Blood Institute, National Institutes of Health, and US Department of Health and Human Services. LaMonte reported receiving grants from the National Institutes of Health during the conduct of the study; see paper for disclosures of the other authors.
 

A version of this article appeared on Medscape.com.

TOPLINE: 

Accelerometer-measured physical activity (PA), whether light, moderate, or vigorous, is associated with lower risk for heart failure (HF) in older women while more sedentary time is associated with higher HF risk in these women, results of a new study suggest. 

METHODOLOGY:

• The analysis included 5951 women aged 63-99 years (mean age, 78.6 years), including 33.7% Black, 17.2% Hispanic, and 49.2% White individuals without HF from the Objective Physical Activity and Cardiovascular Health (OPACH) study, an ancillary to the Women’s Health Initiative Long-Life Study.
• Participants wore an accelerometer on their hip 24 hours a day for up to 7 consecutive days except when in water, kept nightly sleep logs, completed questionnaires to provide information on medical history and sociodemographic and lifestyle factors, and self-rated their general health status.
• Researchers recorded their use of assistive walking devices; determined body mass index as well as blood pressure; obtained fasting serum glucose, total and high-density lipoprotein cholesterol, triglyceride, and high-sensitivity C-reactive protein concentrations; and scored participants’ multimorbidity.
• They determined intensity-specific PA using vector magnitude acceleration cut points (light PA, 19-518 counts/15 s; moderate to vigorous PA [MVPA], > 518) and steps per day using dedicated software, and they quantified sedentary time (total and mean bout duration).
• The primary outcome was overall self-reported HF later adjudicated by physicians using medical record reviews; secondary endpoints were heart failure with reduced ejection fraction (HFrEF) and preserved EF (HFpEF), classified by an EF of < 45% or 45% or > 45%, respectively, after cardiac imaging.

TAKEAWAY:

• A total of 407 HF cases (including 257 HFpEF and 110 HFrEF) were identified during a mean of 7.5 years of follow-up.
• HFrEF was not associated with PA measures in the fully adjusted model (which controlled extensively for health and physical functioning status), but overall HF and HFpEF were inversely associated with total PA (per 1-standard deviation [SD] increment: hazard ratio [HR] 0.85; 95% CI, 0.75-0.95 and HR, 0.78; 95% CI, 0.67-0.91, respectively), light PA (HR, 0.88; 95% CI, 0.78-0.98 and HR, 0.80; 95% CI, 0.70-0.93, respectively) and MVPA (HR, 0.84; 95% CI, 0.73-0.97 and HR, 0.85; 95% CI, 0.72-1.01, respectively).
• With regard to daily steps, each 1-SD increment was associated with a significant 26% lower risk for overall HF (HR 0.74; 95% CI, 0.63-0.88) and 29% lower risk for HFpEF (HR, 0.71; 95% CI, 0.57-0.88), with these inverse risks becoming significant at about 2000 steps/d, “far less than the often touted 10,000 steps/d for promoting health benefits,” noted the authors.
• Total sedentary time was positively associated (per 1 SD in the fully adjusted model) with risks of overall HF (HR, 1.17; 95% CI, 1.04-1.33) and HFpEF (HR, 1.29; 95% CI, 1.10-1.51) but not HFrEF; mean sedentary bout duration was significantly inversely associated with HFrEF (per 1 SD: HR, 0.76; 95% CI, 0.61-0.97), although the relatively small number of cases at the extremes of bout duration may contribute to this unexpected inverse association, said the authors.

IN PRACTICE:

The implications of promoting PA, regardless of intensity, for primary HFpEF prevention in later life, “has profound public health and clinical relevance,” the authors concluded. They noted that HFpEF is a “burgeoning epidemic” that disproportionately affects women and minorities with limited available therapies.

STUDY DETAILS:

The study, led by Michael J. LaMonte, PhD, MPH, University at Buffalo-SUNY, Buffalo, New York, was published online on February 21, 2024, in JAMA Cardiology.

LIMITATIONS:

There was only a single accelerometer assessment of PA and sedentary exposures and relatively small numbers of HFrEF cases, which restricted analytic precision. Although researchers controlled for several established vascular biomarkers, they did not have HF-specific measures such as cardiac troponin or N-terminal pro–brain natriuretic peptide. It’s unknown if the findings can be generalized to men and populations dissimilar to women in OPACH.

DISCLOSURES:

The study was funded in part by the National Heart, Lung, and Blood Institute, National Institutes of Health, and US Department of Health and Human Services. LaMonte reported receiving grants from the National Institutes of Health during the conduct of the study; see paper for disclosures of the other authors.
 

A version of this article appeared on Medscape.com.

TOPLINE: 

Accelerometer-measured physical activity (PA), whether light, moderate, or vigorous, is associated with lower risk for heart failure (HF) in older women while more sedentary time is associated with higher HF risk in these women, results of a new study suggest. 

METHODOLOGY:

• The analysis included 5951 women aged 63-99 years (mean age, 78.6 years), including 33.7% Black, 17.2% Hispanic, and 49.2% White individuals without HF from the Objective Physical Activity and Cardiovascular Health (OPACH) study, an ancillary to the Women’s Health Initiative Long-Life Study.
• Participants wore an accelerometer on their hip 24 hours a day for up to 7 consecutive days except when in water, kept nightly sleep logs, completed questionnaires to provide information on medical history and sociodemographic and lifestyle factors, and self-rated their general health status.
• Researchers recorded their use of assistive walking devices; determined body mass index as well as blood pressure; obtained fasting serum glucose, total and high-density lipoprotein cholesterol, triglyceride, and high-sensitivity C-reactive protein concentrations; and scored participants’ multimorbidity.
• They determined intensity-specific PA using vector magnitude acceleration cut points (light PA, 19-518 counts/15 s; moderate to vigorous PA [MVPA], > 518) and steps per day using dedicated software, and they quantified sedentary time (total and mean bout duration).
• The primary outcome was overall self-reported HF later adjudicated by physicians using medical record reviews; secondary endpoints were heart failure with reduced ejection fraction (HFrEF) and preserved EF (HFpEF), classified by an EF of < 45% or 45% or > 45%, respectively, after cardiac imaging.

TAKEAWAY:

• A total of 407 HF cases (including 257 HFpEF and 110 HFrEF) were identified during a mean of 7.5 years of follow-up.
• HFrEF was not associated with PA measures in the fully adjusted model (which controlled extensively for health and physical functioning status), but overall HF and HFpEF were inversely associated with total PA (per 1-standard deviation [SD] increment: hazard ratio [HR] 0.85; 95% CI, 0.75-0.95 and HR, 0.78; 95% CI, 0.67-0.91, respectively), light PA (HR, 0.88; 95% CI, 0.78-0.98 and HR, 0.80; 95% CI, 0.70-0.93, respectively) and MVPA (HR, 0.84; 95% CI, 0.73-0.97 and HR, 0.85; 95% CI, 0.72-1.01, respectively).
• With regard to daily steps, each 1-SD increment was associated with a significant 26% lower risk for overall HF (HR 0.74; 95% CI, 0.63-0.88) and 29% lower risk for HFpEF (HR, 0.71; 95% CI, 0.57-0.88), with these inverse risks becoming significant at about 2000 steps/d, “far less than the often touted 10,000 steps/d for promoting health benefits,” noted the authors.
• Total sedentary time was positively associated (per 1 SD in the fully adjusted model) with risks of overall HF (HR, 1.17; 95% CI, 1.04-1.33) and HFpEF (HR, 1.29; 95% CI, 1.10-1.51) but not HFrEF; mean sedentary bout duration was significantly inversely associated with HFrEF (per 1 SD: HR, 0.76; 95% CI, 0.61-0.97), although the relatively small number of cases at the extremes of bout duration may contribute to this unexpected inverse association, said the authors.

IN PRACTICE:

The implications of promoting PA, regardless of intensity, for primary HFpEF prevention in later life, “has profound public health and clinical relevance,” the authors concluded. They noted that HFpEF is a “burgeoning epidemic” that disproportionately affects women and minorities with limited available therapies.

STUDY DETAILS:

The study, led by Michael J. LaMonte, PhD, MPH, University at Buffalo-SUNY, Buffalo, New York, was published online on February 21, 2024, in JAMA Cardiology.

LIMITATIONS:

There was only a single accelerometer assessment of PA and sedentary exposures and relatively small numbers of HFrEF cases, which restricted analytic precision. Although researchers controlled for several established vascular biomarkers, they did not have HF-specific measures such as cardiac troponin or N-terminal pro–brain natriuretic peptide. It’s unknown if the findings can be generalized to men and populations dissimilar to women in OPACH.

DISCLOSURES:

The study was funded in part by the National Heart, Lung, and Blood Institute, National Institutes of Health, and US Department of Health and Human Services. LaMonte reported receiving grants from the National Institutes of Health during the conduct of the study; see paper for disclosures of the other authors.
 

A version of this article appeared on Medscape.com.

PHOENIX — Adding either argatroban or eptifibatide to thrombolytic therapy doesn’t improve function following an ischemic stroke, results of new research show. 

“Ultimately, we found no benefit for either medication added to standard-of-care thrombolysis in terms of improving stroke outcomes,” said lead study author Opeolu M. Adeoye, MD, professor of emergency medicine and department chair, Washington University School of Medicine, St. Louis, Missouri. 

The results were surprising and disappointing for Dr. Adeoye. “We went into the trial hopeful and thinking we would be able to benefit patients in reducing disability from stroke,” he said. 

The Multi-Arm Optimization of Stroke Thrombolysis (MOST) trial was stopped early because of futility following recommendations from the data and safety monitoring board.

The findings were presented at the International Stroke Conference presented by the American Stroke Association, a division of the American Heart Association.

A thrombolytic drug alone doesn’t help all patients, particularly those with larger clots. “Clots can open; they can reform; they can re-occlude, etc.,” said another author, Andrew D. Barreto, MD, associate professor, Department of Neurology, University of Texas Health Science Center, Houston. “The thought was that adding additional medications that thin the blood, like argatroban or eptifibatide, would amplify the effects of the clot-busting drug.” 

Indeed, this approach has had success in cardiology in terms of blood vessel opening, said Dr. Adeoye, adding that some preclinical data suggest that antithrombotic drugs may be neuroprotective. 

Six phase 2 studies going back over a dozen years suggested that these drugs are safe in stroke patients. Although these studies weren’t powered for efficacy, “we did see a signal that adding them would be better than just the clot-busting drug alone.” These findings prompted the current phase 3 trial, said Dr. Barreto. 

The three-arm, single-blind MOST trial included 514 adult patients with acute ischemic stroke and a National Institutes of Health Stroke Scale (NIHSS) score of 6 or greater at 57 US centers. In the study cohort the mean age was about 68 years, 70% White/25% Black, and with about equal numbers of female and male patients.

All received standard stroke care including thrombolysis within 3 hours of symptom onset. Initially, researchers used intravenous alteplase (0.9 mg/kg), but as the standard of care changed over time, they began using tenecteplase (0.25 mg/kg).

Study patients were also randomly assigned to receive placebo or either argatroban (100 mcg/kg bolus followed by 3 mcg/kg per minute for 12 hours) or eptifibatide (135 mcg/kg bolus followed by 0.75 mcg/kg/min infusion for 2 hours). These treatments were initiated within 75 minutes of thrombolysis.
 

Two Different Mechanisms

The drugs have different mechanisms of action. Argatroban is an anticoagulant, a direct inhibitor of thrombin, while the antiplatelet eptifibatide blocks the glycoprotein IIb/IIIa receptor and was specifically developed to ensure rapid inhibition of platelet aggregation.

Patients could also receive endovascular thrombectomy as part of their usual care. In this study, about 44% of patients received this treatment.

The primary endpoint was 90-day utility weighted modified Rankin Scale (uw-mRS) scores, where the worst outcome is 0 and the best outcome is 10.

The study used a response-adaptive randomization design, where the randomization switches from a drug that doesn’t appear to have a chance of working to the arm more likely to be beneficial. 

Of the 514 patients, the analysis included 228 in the placebo, 59 in the argatroban, and 227 in eptifibatide groups. Of the total, 421 completed the study. 

The mean 90-day uw-mRS was 6.8 in the placebo group, 5.2 in the argatroban group, and 6.3 in the eptifibatide group.

The probability of argatroban being better than placebo was 0.2%; the probability of eptifibatide being better than placebo was 0.9%. The futility threshold was enrollment of 500 and less than a 20% chance of benefit, thus the decision to stop the trial. 

In all subgroup analyses, which looked at age, stroke severity, the two thrombolytic drugs, and use of endovascular therapy, “we didn’t really see much of a signal that would suggest that’s the group we would need to be testing further,” said Dr. Barreto. 
 

No Increased ICH Risk

The primary safety outcome was symptomatic intracranial hemorrhage within 36 hours of randomization. The researchers found no significant increase in rates of this outcome.

The argatroban cohort had significantly lower odds of favorable outcomes compared with placebo, noted Dr. Adeoye. For example, it had more all-cause deaths, although none were related to the study drug. 

Speculating on why the intervention didn’t work, Dr. Barreto pointed to changes in standard of care between the earlier trials and the current one, including the incorporation of endovascular therapy and switch to tenecteplase. 

Although the results were disappointing, Dr. Adeoye sees a bright side. “What we’re very proud of, and excited about, is the fact that we have a definitive answer on these two drugs, and we did it in one trial as opposed to sequential, separate ongoing trials.” 

But he stressed that more work needs to be done, especially given that even with endovascular therapy, half of stroke patients don’t achieve independence. 

“In this trial, we established that argatroban and eptifibatide added to thrombolysis did not work, but that doesn’t address the fact that we need to continue to see what we can do to improve the total proportion of stroke patients who, after our treatments, are functionally independent 90 days after the stroke.” 
 

Down the Rabbit Hole

Commenting on the research, Larry B. Goldstein, MD, professor and chair, Department of Neurology, University of Kentucky, Lexington, praised the study’s adaptive design, noted that the hypothesis the study was based on was “reasonable” given the concern about additional thromboses, and found the results useful. 

“The goal is not only to see what works but also what doesn’t work so we don’t go down that rabbit hole.” 

He also pointed out that because the two blood-thinning drugs studied have very different mechanisms of action, it’s unlikely that another antithrombotic would add benefit to thrombolysis, “but you never say never.” 

Dr. Adeoye and Dr. Barreto report research funding from the National Institutes of Health/National Institute of Neurological Disorders and Stroke. Dr. Adeoye also reports an executive role, receiving royalties/being a patent beneficiary, Sense Diagnostics, Inc. Dr. Goldstein has no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

PHOENIX — Adding either argatroban or eptifibatide to thrombolytic therapy doesn’t improve function following an ischemic stroke, results of new research show. 

“Ultimately, we found no benefit for either medication added to standard-of-care thrombolysis in terms of improving stroke outcomes,” said lead study author Opeolu M. Adeoye, MD, professor of emergency medicine and department chair, Washington University School of Medicine, St. Louis, Missouri. 

The results were surprising and disappointing for Dr. Adeoye. “We went into the trial hopeful and thinking we would be able to benefit patients in reducing disability from stroke,” he said. 

The Multi-Arm Optimization of Stroke Thrombolysis (MOST) trial was stopped early because of futility following recommendations from the data and safety monitoring board.

The findings were presented at the International Stroke Conference presented by the American Stroke Association, a division of the American Heart Association.

A thrombolytic drug alone doesn’t help all patients, particularly those with larger clots. “Clots can open; they can reform; they can re-occlude, etc.,” said another author, Andrew D. Barreto, MD, associate professor, Department of Neurology, University of Texas Health Science Center, Houston. “The thought was that adding additional medications that thin the blood, like argatroban or eptifibatide, would amplify the effects of the clot-busting drug.” 

Indeed, this approach has had success in cardiology in terms of blood vessel opening, said Dr. Adeoye, adding that some preclinical data suggest that antithrombotic drugs may be neuroprotective. 

Six phase 2 studies going back over a dozen years suggested that these drugs are safe in stroke patients. Although these studies weren’t powered for efficacy, “we did see a signal that adding them would be better than just the clot-busting drug alone.” These findings prompted the current phase 3 trial, said Dr. Barreto. 

The three-arm, single-blind MOST trial included 514 adult patients with acute ischemic stroke and a National Institutes of Health Stroke Scale (NIHSS) score of 6 or greater at 57 US centers. In the study cohort the mean age was about 68 years, 70% White/25% Black, and with about equal numbers of female and male patients.

All received standard stroke care including thrombolysis within 3 hours of symptom onset. Initially, researchers used intravenous alteplase (0.9 mg/kg), but as the standard of care changed over time, they began using tenecteplase (0.25 mg/kg).

Study patients were also randomly assigned to receive placebo or either argatroban (100 mcg/kg bolus followed by 3 mcg/kg per minute for 12 hours) or eptifibatide (135 mcg/kg bolus followed by 0.75 mcg/kg/min infusion for 2 hours). These treatments were initiated within 75 minutes of thrombolysis.
 

Two Different Mechanisms

The drugs have different mechanisms of action. Argatroban is an anticoagulant, a direct inhibitor of thrombin, while the antiplatelet eptifibatide blocks the glycoprotein IIb/IIIa receptor and was specifically developed to ensure rapid inhibition of platelet aggregation.

Patients could also receive endovascular thrombectomy as part of their usual care. In this study, about 44% of patients received this treatment.

The primary endpoint was 90-day utility weighted modified Rankin Scale (uw-mRS) scores, where the worst outcome is 0 and the best outcome is 10.

The study used a response-adaptive randomization design, where the randomization switches from a drug that doesn’t appear to have a chance of working to the arm more likely to be beneficial. 

Of the 514 patients, the analysis included 228 in the placebo, 59 in the argatroban, and 227 in eptifibatide groups. Of the total, 421 completed the study. 

The mean 90-day uw-mRS was 6.8 in the placebo group, 5.2 in the argatroban group, and 6.3 in the eptifibatide group.

The probability of argatroban being better than placebo was 0.2%; the probability of eptifibatide being better than placebo was 0.9%. The futility threshold was enrollment of 500 and less than a 20% chance of benefit, thus the decision to stop the trial. 

In all subgroup analyses, which looked at age, stroke severity, the two thrombolytic drugs, and use of endovascular therapy, “we didn’t really see much of a signal that would suggest that’s the group we would need to be testing further,” said Dr. Barreto. 
 

No Increased ICH Risk

The primary safety outcome was symptomatic intracranial hemorrhage within 36 hours of randomization. The researchers found no significant increase in rates of this outcome.

The argatroban cohort had significantly lower odds of favorable outcomes compared with placebo, noted Dr. Adeoye. For example, it had more all-cause deaths, although none were related to the study drug. 

Speculating on why the intervention didn’t work, Dr. Barreto pointed to changes in standard of care between the earlier trials and the current one, including the incorporation of endovascular therapy and switch to tenecteplase. 

Although the results were disappointing, Dr. Adeoye sees a bright side. “What we’re very proud of, and excited about, is the fact that we have a definitive answer on these two drugs, and we did it in one trial as opposed to sequential, separate ongoing trials.” 

But he stressed that more work needs to be done, especially given that even with endovascular therapy, half of stroke patients don’t achieve independence. 

“In this trial, we established that argatroban and eptifibatide added to thrombolysis did not work, but that doesn’t address the fact that we need to continue to see what we can do to improve the total proportion of stroke patients who, after our treatments, are functionally independent 90 days after the stroke.” 
 

Down the Rabbit Hole

Commenting on the research, Larry B. Goldstein, MD, professor and chair, Department of Neurology, University of Kentucky, Lexington, praised the study’s adaptive design, noted that the hypothesis the study was based on was “reasonable” given the concern about additional thromboses, and found the results useful. 

“The goal is not only to see what works but also what doesn’t work so we don’t go down that rabbit hole.” 

He also pointed out that because the two blood-thinning drugs studied have very different mechanisms of action, it’s unlikely that another antithrombotic would add benefit to thrombolysis, “but you never say never.” 

Dr. Adeoye and Dr. Barreto report research funding from the National Institutes of Health/National Institute of Neurological Disorders and Stroke. Dr. Adeoye also reports an executive role, receiving royalties/being a patent beneficiary, Sense Diagnostics, Inc. Dr. Goldstein has no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

PHOENIX — Adding either argatroban or eptifibatide to thrombolytic therapy doesn’t improve function following an ischemic stroke, results of new research show. 

“Ultimately, we found no benefit for either medication added to standard-of-care thrombolysis in terms of improving stroke outcomes,” said lead study author Opeolu M. Adeoye, MD, professor of emergency medicine and department chair, Washington University School of Medicine, St. Louis, Missouri. 

The results were surprising and disappointing for Dr. Adeoye. “We went into the trial hopeful and thinking we would be able to benefit patients in reducing disability from stroke,” he said. 

The Multi-Arm Optimization of Stroke Thrombolysis (MOST) trial was stopped early because of futility following recommendations from the data and safety monitoring board.

The findings were presented at the International Stroke Conference presented by the American Stroke Association, a division of the American Heart Association.

A thrombolytic drug alone doesn’t help all patients, particularly those with larger clots. “Clots can open; they can reform; they can re-occlude, etc.,” said another author, Andrew D. Barreto, MD, associate professor, Department of Neurology, University of Texas Health Science Center, Houston. “The thought was that adding additional medications that thin the blood, like argatroban or eptifibatide, would amplify the effects of the clot-busting drug.” 

Indeed, this approach has had success in cardiology in terms of blood vessel opening, said Dr. Adeoye, adding that some preclinical data suggest that antithrombotic drugs may be neuroprotective. 

Six phase 2 studies going back over a dozen years suggested that these drugs are safe in stroke patients. Although these studies weren’t powered for efficacy, “we did see a signal that adding them would be better than just the clot-busting drug alone.” These findings prompted the current phase 3 trial, said Dr. Barreto. 

The three-arm, single-blind MOST trial included 514 adult patients with acute ischemic stroke and a National Institutes of Health Stroke Scale (NIHSS) score of 6 or greater at 57 US centers. In the study cohort the mean age was about 68 years, 70% White/25% Black, and with about equal numbers of female and male patients.

All received standard stroke care including thrombolysis within 3 hours of symptom onset. Initially, researchers used intravenous alteplase (0.9 mg/kg), but as the standard of care changed over time, they began using tenecteplase (0.25 mg/kg).

Study patients were also randomly assigned to receive placebo or either argatroban (100 mcg/kg bolus followed by 3 mcg/kg per minute for 12 hours) or eptifibatide (135 mcg/kg bolus followed by 0.75 mcg/kg/min infusion for 2 hours). These treatments were initiated within 75 minutes of thrombolysis.
 

Two Different Mechanisms

The drugs have different mechanisms of action. Argatroban is an anticoagulant, a direct inhibitor of thrombin, while the antiplatelet eptifibatide blocks the glycoprotein IIb/IIIa receptor and was specifically developed to ensure rapid inhibition of platelet aggregation.

Patients could also receive endovascular thrombectomy as part of their usual care. In this study, about 44% of patients received this treatment.

The primary endpoint was 90-day utility weighted modified Rankin Scale (uw-mRS) scores, where the worst outcome is 0 and the best outcome is 10.

The study used a response-adaptive randomization design, where the randomization switches from a drug that doesn’t appear to have a chance of working to the arm more likely to be beneficial. 

Of the 514 patients, the analysis included 228 in the placebo, 59 in the argatroban, and 227 in eptifibatide groups. Of the total, 421 completed the study. 

The mean 90-day uw-mRS was 6.8 in the placebo group, 5.2 in the argatroban group, and 6.3 in the eptifibatide group.

The probability of argatroban being better than placebo was 0.2%; the probability of eptifibatide being better than placebo was 0.9%. The futility threshold was enrollment of 500 and less than a 20% chance of benefit, thus the decision to stop the trial. 

In all subgroup analyses, which looked at age, stroke severity, the two thrombolytic drugs, and use of endovascular therapy, “we didn’t really see much of a signal that would suggest that’s the group we would need to be testing further,” said Dr. Barreto. 
 

No Increased ICH Risk

The primary safety outcome was symptomatic intracranial hemorrhage within 36 hours of randomization. The researchers found no significant increase in rates of this outcome.

The argatroban cohort had significantly lower odds of favorable outcomes compared with placebo, noted Dr. Adeoye. For example, it had more all-cause deaths, although none were related to the study drug. 

Speculating on why the intervention didn’t work, Dr. Barreto pointed to changes in standard of care between the earlier trials and the current one, including the incorporation of endovascular therapy and switch to tenecteplase. 

Although the results were disappointing, Dr. Adeoye sees a bright side. “What we’re very proud of, and excited about, is the fact that we have a definitive answer on these two drugs, and we did it in one trial as opposed to sequential, separate ongoing trials.” 

But he stressed that more work needs to be done, especially given that even with endovascular therapy, half of stroke patients don’t achieve independence. 

“In this trial, we established that argatroban and eptifibatide added to thrombolysis did not work, but that doesn’t address the fact that we need to continue to see what we can do to improve the total proportion of stroke patients who, after our treatments, are functionally independent 90 days after the stroke.” 
 

Down the Rabbit Hole

Commenting on the research, Larry B. Goldstein, MD, professor and chair, Department of Neurology, University of Kentucky, Lexington, praised the study’s adaptive design, noted that the hypothesis the study was based on was “reasonable” given the concern about additional thromboses, and found the results useful. 

“The goal is not only to see what works but also what doesn’t work so we don’t go down that rabbit hole.” 

He also pointed out that because the two blood-thinning drugs studied have very different mechanisms of action, it’s unlikely that another antithrombotic would add benefit to thrombolysis, “but you never say never.” 

Dr. Adeoye and Dr. Barreto report research funding from the National Institutes of Health/National Institute of Neurological Disorders and Stroke. Dr. Adeoye also reports an executive role, receiving royalties/being a patent beneficiary, Sense Diagnostics, Inc. Dr. Goldstein has no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

A universal cardiovascular disease (CVD) prediction tool performs well in patients with and without atherosclerotic CVD (ASCVD), a new study showed, suggesting this model could facilitate transition from primary to secondary prevention by streamlining risk classification.

METHODOLOGY:

• Researchers used different models to evaluate whether established CVD predictors, including age, sex, race, diabetes, systolic blood pressure, or smoking, are associated with major adverse cardiovascular events (MACEs), including myocardial infarction (MI), stroke, and heart failure (HF), among 9138 patients, mean age 63.8 years, in the Atherosclerosis Risk in Communities (ARIC) study.
• Of these, 609 had ASCVD (history of MI, ischemic stroke, or symptomatic peripheral artery disease) and 8529 did not.
• They extended their exploration to other predictors available in clinical practice, including family history of premature ASCVD, high-sensitivity C-reactive protein, lipoprotein(a), triglycerides, and apolipoprotein B, as well as predictors of HF such as body mass index and heart rate and blood-based cardiac biomarkers.
• An external validation analysis included 5322 participants in the Multi-Ethnic Study of Atherosclerosis (MESA).
• Over a median follow-up of 18.9 years, 3209 ARIC participants (35%) developed MACE for an incidence rate per 1000 person-years of 21.3 for MACE, 12.6 for MI/stroke, and 13.8 for HF.

TAKEAWAY:

• Of all candidate predictors, 10 variables (including established predictors and cardiac biomarkers) were included in the universal prediction model, which demonstrated good calibration in both those with ASCVD (hazard ratio [HR] C-statistic, 0.692; 95% CI, 0.650-0.735) and without ASCVD (HR C-statistic, 0.748; 95% CI, 0.726-0.770).
• As anticipated, the risk for MACE was generally lower in those with no prior ASCVD, but the 5-year risk in the highest quintile of predicted risk in those without ASCVD was higher than that in the lowest two quintiles of the ASCVD group.
• The universal risk prediction model was validated in the MESA community–based cohort; over a median follow-up of 13.7 years, 12% of participants with and without prior ASCVD developed MACE for an incidence rate per 1000 person-years of 10.2 for MACE, 7.4 for MI/stroke, and 4.3 for HF.
• The results were generally similar when examining individual outcomes (MI/stroke and HF) and for both no ASCVD and ASCVD groups across demographic subgroups by age, sex, and race.

IN PRACTICE:

The findings “support the importance of established predictors for classifying long-term CVD risk in both primary and secondary prevention settings,” the authors wrote, adding an advantage to this risk prediction approach could be to help providers and patients “further personalize secondary prevention.”

In an accompanying editorial, Pier Sergio Saba, MD, PhD, Clinical and Interventional Cardiology, Sassari University Hospital, Sassari, Italy, and others said the universal risk assessment approach “is conceptually promising” but noted patients with ASCVD represented only 7% of the study population, and this population was relatively young, potentially limiting the applicability of this risk model in older individuals. Before the risk model can be used in clinical settings, results need to be validated and given incorporation of cardiac biomarkers, “careful cost-benefit analyses may also be needed,” the editorial writers added.

SOURCE:

The study was conducted by Yejin Mok, PHD, MPH, Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, and colleagues. It was published online on January 29, 2024, in the Journal of the American College of Cardiology (JACC).

LIMITATIONS:

The somewhat limited number of study participants with prior ASCVD precluded researchers from quantifying the prognostic impact of ASCVD subtypes (eg, history of MI vs stroke vs peripheral artery disease). The study didn’t have data on some predictors recognized in guidelines (eg, coronary artery calcium and left ventricular ejection fraction). The ARIC analysis included only Black and White participants, and although models were validated in MESA, which included Chinese and Hispanic adults, extrapolation of results to more racially/ethnically diverse populations should be done with care.

DISCLOSURES:

The ARIC study received funding from the National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health, and Department of Health and Human Services. The MESA study was supported by the NHLBI and National Center for Advancing Translational Sciences. The study authors and editorial writers had no relevant conflicts of interest.

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

TOPLINE:

A universal cardiovascular disease (CVD) prediction tool performs well in patients with and without atherosclerotic CVD (ASCVD), a new study showed, suggesting this model could facilitate transition from primary to secondary prevention by streamlining risk classification.

METHODOLOGY:

• Researchers used different models to evaluate whether established CVD predictors, including age, sex, race, diabetes, systolic blood pressure, or smoking, are associated with major adverse cardiovascular events (MACEs), including myocardial infarction (MI), stroke, and heart failure (HF), among 9138 patients, mean age 63.8 years, in the Atherosclerosis Risk in Communities (ARIC) study.
• Of these, 609 had ASCVD (history of MI, ischemic stroke, or symptomatic peripheral artery disease) and 8529 did not.
• They extended their exploration to other predictors available in clinical practice, including family history of premature ASCVD, high-sensitivity C-reactive protein, lipoprotein(a), triglycerides, and apolipoprotein B, as well as predictors of HF such as body mass index and heart rate and blood-based cardiac biomarkers.
• An external validation analysis included 5322 participants in the Multi-Ethnic Study of Atherosclerosis (MESA).
• Over a median follow-up of 18.9 years, 3209 ARIC participants (35%) developed MACE for an incidence rate per 1000 person-years of 21.3 for MACE, 12.6 for MI/stroke, and 13.8 for HF.

TAKEAWAY:

• Of all candidate predictors, 10 variables (including established predictors and cardiac biomarkers) were included in the universal prediction model, which demonstrated good calibration in both those with ASCVD (hazard ratio [HR] C-statistic, 0.692; 95% CI, 0.650-0.735) and without ASCVD (HR C-statistic, 0.748; 95% CI, 0.726-0.770).
• As anticipated, the risk for MACE was generally lower in those with no prior ASCVD, but the 5-year risk in the highest quintile of predicted risk in those without ASCVD was higher than that in the lowest two quintiles of the ASCVD group.
• The universal risk prediction model was validated in the MESA community–based cohort; over a median follow-up of 13.7 years, 12% of participants with and without prior ASCVD developed MACE for an incidence rate per 1000 person-years of 10.2 for MACE, 7.4 for MI/stroke, and 4.3 for HF.
• The results were generally similar when examining individual outcomes (MI/stroke and HF) and for both no ASCVD and ASCVD groups across demographic subgroups by age, sex, and race.

IN PRACTICE:

The findings “support the importance of established predictors for classifying long-term CVD risk in both primary and secondary prevention settings,” the authors wrote, adding an advantage to this risk prediction approach could be to help providers and patients “further personalize secondary prevention.”

In an accompanying editorial, Pier Sergio Saba, MD, PhD, Clinical and Interventional Cardiology, Sassari University Hospital, Sassari, Italy, and others said the universal risk assessment approach “is conceptually promising” but noted patients with ASCVD represented only 7% of the study population, and this population was relatively young, potentially limiting the applicability of this risk model in older individuals. Before the risk model can be used in clinical settings, results need to be validated and given incorporation of cardiac biomarkers, “careful cost-benefit analyses may also be needed,” the editorial writers added.

SOURCE:

The study was conducted by Yejin Mok, PHD, MPH, Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, and colleagues. It was published online on January 29, 2024, in the Journal of the American College of Cardiology (JACC).

LIMITATIONS:

The somewhat limited number of study participants with prior ASCVD precluded researchers from quantifying the prognostic impact of ASCVD subtypes (eg, history of MI vs stroke vs peripheral artery disease). The study didn’t have data on some predictors recognized in guidelines (eg, coronary artery calcium and left ventricular ejection fraction). The ARIC analysis included only Black and White participants, and although models were validated in MESA, which included Chinese and Hispanic adults, extrapolation of results to more racially/ethnically diverse populations should be done with care.

DISCLOSURES:

The ARIC study received funding from the National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health, and Department of Health and Human Services. The MESA study was supported by the NHLBI and National Center for Advancing Translational Sciences. The study authors and editorial writers had no relevant conflicts of interest.

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

TOPLINE:

A universal cardiovascular disease (CVD) prediction tool performs well in patients with and without atherosclerotic CVD (ASCVD), a new study showed, suggesting this model could facilitate transition from primary to secondary prevention by streamlining risk classification.

METHODOLOGY:

• Researchers used different models to evaluate whether established CVD predictors, including age, sex, race, diabetes, systolic blood pressure, or smoking, are associated with major adverse cardiovascular events (MACEs), including myocardial infarction (MI), stroke, and heart failure (HF), among 9138 patients, mean age 63.8 years, in the Atherosclerosis Risk in Communities (ARIC) study.
• Of these, 609 had ASCVD (history of MI, ischemic stroke, or symptomatic peripheral artery disease) and 8529 did not.
• They extended their exploration to other predictors available in clinical practice, including family history of premature ASCVD, high-sensitivity C-reactive protein, lipoprotein(a), triglycerides, and apolipoprotein B, as well as predictors of HF such as body mass index and heart rate and blood-based cardiac biomarkers.
• An external validation analysis included 5322 participants in the Multi-Ethnic Study of Atherosclerosis (MESA).
• Over a median follow-up of 18.9 years, 3209 ARIC participants (35%) developed MACE for an incidence rate per 1000 person-years of 21.3 for MACE, 12.6 for MI/stroke, and 13.8 for HF.

TAKEAWAY:

• Of all candidate predictors, 10 variables (including established predictors and cardiac biomarkers) were included in the universal prediction model, which demonstrated good calibration in both those with ASCVD (hazard ratio [HR] C-statistic, 0.692; 95% CI, 0.650-0.735) and without ASCVD (HR C-statistic, 0.748; 95% CI, 0.726-0.770).
• As anticipated, the risk for MACE was generally lower in those with no prior ASCVD, but the 5-year risk in the highest quintile of predicted risk in those without ASCVD was higher than that in the lowest two quintiles of the ASCVD group.
• The universal risk prediction model was validated in the MESA community–based cohort; over a median follow-up of 13.7 years, 12% of participants with and without prior ASCVD developed MACE for an incidence rate per 1000 person-years of 10.2 for MACE, 7.4 for MI/stroke, and 4.3 for HF.
• The results were generally similar when examining individual outcomes (MI/stroke and HF) and for both no ASCVD and ASCVD groups across demographic subgroups by age, sex, and race.

IN PRACTICE:

The findings “support the importance of established predictors for classifying long-term CVD risk in both primary and secondary prevention settings,” the authors wrote, adding an advantage to this risk prediction approach could be to help providers and patients “further personalize secondary prevention.”

In an accompanying editorial, Pier Sergio Saba, MD, PhD, Clinical and Interventional Cardiology, Sassari University Hospital, Sassari, Italy, and others said the universal risk assessment approach “is conceptually promising” but noted patients with ASCVD represented only 7% of the study population, and this population was relatively young, potentially limiting the applicability of this risk model in older individuals. Before the risk model can be used in clinical settings, results need to be validated and given incorporation of cardiac biomarkers, “careful cost-benefit analyses may also be needed,” the editorial writers added.

SOURCE:

The study was conducted by Yejin Mok, PHD, MPH, Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, and colleagues. It was published online on January 29, 2024, in the Journal of the American College of Cardiology (JACC).

LIMITATIONS:

The somewhat limited number of study participants with prior ASCVD precluded researchers from quantifying the prognostic impact of ASCVD subtypes (eg, history of MI vs stroke vs peripheral artery disease). The study didn’t have data on some predictors recognized in guidelines (eg, coronary artery calcium and left ventricular ejection fraction). The ARIC analysis included only Black and White participants, and although models were validated in MESA, which included Chinese and Hispanic adults, extrapolation of results to more racially/ethnically diverse populations should be done with care.

DISCLOSURES:

The ARIC study received funding from the National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health, and Department of Health and Human Services. The MESA study was supported by the NHLBI and National Center for Advancing Translational Sciences. The study authors and editorial writers had no relevant conflicts of interest.

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

TOPLINE:

Social frailty, the lack of resources to meet basic social needs, is associated with an increased risk for motoric cognitive risk syndrome (MCR), a predementia syndrome characterized by cognitive complaints and slow gait, results of a large, population-based study suggested.

METHODOLOGY:

• The study used 2011 (Round 1) to 2018 (Round 8) data on a discovery sample of 4657 individuals without MCR or dementia at baseline from the National Health and Aging Trends Study (NHATS), a longitudinal survey of older adult Medicare beneficiaries.
• Researchers also collected data on 3075 newly recruited individuals in Round 5 and followed to Round 8 as an independent validation sample to create a pooled sample of 7732 older adults, mean age 76.06, without MCR at baseline.
• Social frailty, assessed at baseline, included five social items: Going out less, not feeling confident, rarely visiting friends/family, not talking with others, and without live-in partner/spouse (researchers divided participants into normal [zero to one items] and social frailty [two to five items] groups).
• Individuals were considered to have MCR if they had both subjective cognitive complaints and slow gait speed (greater than 1 standard deviation below age-specific level) without dementia or mobility disability.
• Covariates included demographic and lifestyle data, presence of depression and/or anxiety symptoms, and number of chronic diseases.

TAKEAWAY:

• During a median follow-up period of 4 years, 10.35% individuals were diagnosed with MCR.
• After the researchers controlled for confounding factors, those with social frailty had an increased risk for MCR compared with the normal group (pooled sample: hazard ratio [HR], 1.57; 95% CI, 1.34-1.84; P < .001).
• Each additional unfavorable social item was associated with an increased risk for MCR (pooled sample: HR, 1.32; 95% CI, 1.22-1.43; P < .001).
• Results of stratified analyses across subgroups suggested individuals with social frailty had a significantly higher risk for incident MCR than that of those without social frailty, regardless of socioeconomic status, lifestyle factors, chronic diseases, and mental health.

IN PRACTICE:

The findings suggest assessing social frailty using simple questions “is an efficient tool for detecting older individuals with a high risk of MCR,” the authors wrote. They noted that the addition of such a tool in clinical practice may facilitate “timely implementation of prevention strategies.”

SOURCE:

The research was led by Hui Zhang, Human Phenome Institute, Zhangjiang Fudan International Innovation Centre, Fudan University, Shanghai, China. It was published online on January 29, 2024, in Alzheimer’s & Dementia.

LIMITATIONS:

The study was observational, so the association between social frailty and MCR is merely correlational. Due to the lack of genetic information in NHATS data, researchers didn’t evaluate the effect of genetic factors such as apolipoprotein E on the association between social frailty and MCR. Social frailty was assessed at a single time point. In addition, the researchers were unable examine the time sequence between social frailty and MCR and so could not determine the cause of this association.

DISCLOSURES:

The study was supported by the National Natural Science Foundation of China-Youth Science Fund, Shanghai Rising-Star Program, Shanghai Municipal Health Commission and Key Discipline Construction Project of Pudong Health, and Family Planning Commission of Shanghai. The authors reported no relevant conflicts of interest.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Social frailty, the lack of resources to meet basic social needs, is associated with an increased risk for motoric cognitive risk syndrome (MCR), a predementia syndrome characterized by cognitive complaints and slow gait, results of a large, population-based study suggested.

METHODOLOGY:

• The study used 2011 (Round 1) to 2018 (Round 8) data on a discovery sample of 4657 individuals without MCR or dementia at baseline from the National Health and Aging Trends Study (NHATS), a longitudinal survey of older adult Medicare beneficiaries.
• Researchers also collected data on 3075 newly recruited individuals in Round 5 and followed to Round 8 as an independent validation sample to create a pooled sample of 7732 older adults, mean age 76.06, without MCR at baseline.
• Social frailty, assessed at baseline, included five social items: Going out less, not feeling confident, rarely visiting friends/family, not talking with others, and without live-in partner/spouse (researchers divided participants into normal [zero to one items] and social frailty [two to five items] groups).
• Individuals were considered to have MCR if they had both subjective cognitive complaints and slow gait speed (greater than 1 standard deviation below age-specific level) without dementia or mobility disability.
• Covariates included demographic and lifestyle data, presence of depression and/or anxiety symptoms, and number of chronic diseases.

TAKEAWAY:

• During a median follow-up period of 4 years, 10.35% individuals were diagnosed with MCR.
• After the researchers controlled for confounding factors, those with social frailty had an increased risk for MCR compared with the normal group (pooled sample: hazard ratio [HR], 1.57; 95% CI, 1.34-1.84; P < .001).
• Each additional unfavorable social item was associated with an increased risk for MCR (pooled sample: HR, 1.32; 95% CI, 1.22-1.43; P < .001).
• Results of stratified analyses across subgroups suggested individuals with social frailty had a significantly higher risk for incident MCR than that of those without social frailty, regardless of socioeconomic status, lifestyle factors, chronic diseases, and mental health.

IN PRACTICE:

The findings suggest assessing social frailty using simple questions “is an efficient tool for detecting older individuals with a high risk of MCR,” the authors wrote. They noted that the addition of such a tool in clinical practice may facilitate “timely implementation of prevention strategies.”

SOURCE:

The research was led by Hui Zhang, Human Phenome Institute, Zhangjiang Fudan International Innovation Centre, Fudan University, Shanghai, China. It was published online on January 29, 2024, in Alzheimer’s & Dementia.

LIMITATIONS:

The study was observational, so the association between social frailty and MCR is merely correlational. Due to the lack of genetic information in NHATS data, researchers didn’t evaluate the effect of genetic factors such as apolipoprotein E on the association between social frailty and MCR. Social frailty was assessed at a single time point. In addition, the researchers were unable examine the time sequence between social frailty and MCR and so could not determine the cause of this association.

DISCLOSURES:

The study was supported by the National Natural Science Foundation of China-Youth Science Fund, Shanghai Rising-Star Program, Shanghai Municipal Health Commission and Key Discipline Construction Project of Pudong Health, and Family Planning Commission of Shanghai. The authors reported no relevant conflicts of interest.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Social frailty, the lack of resources to meet basic social needs, is associated with an increased risk for motoric cognitive risk syndrome (MCR), a predementia syndrome characterized by cognitive complaints and slow gait, results of a large, population-based study suggested.

METHODOLOGY:

• The study used 2011 (Round 1) to 2018 (Round 8) data on a discovery sample of 4657 individuals without MCR or dementia at baseline from the National Health and Aging Trends Study (NHATS), a longitudinal survey of older adult Medicare beneficiaries.
• Researchers also collected data on 3075 newly recruited individuals in Round 5 and followed to Round 8 as an independent validation sample to create a pooled sample of 7732 older adults, mean age 76.06, without MCR at baseline.
• Social frailty, assessed at baseline, included five social items: Going out less, not feeling confident, rarely visiting friends/family, not talking with others, and without live-in partner/spouse (researchers divided participants into normal [zero to one items] and social frailty [two to five items] groups).
• Individuals were considered to have MCR if they had both subjective cognitive complaints and slow gait speed (greater than 1 standard deviation below age-specific level) without dementia or mobility disability.
• Covariates included demographic and lifestyle data, presence of depression and/or anxiety symptoms, and number of chronic diseases.

TAKEAWAY:

• During a median follow-up period of 4 years, 10.35% individuals were diagnosed with MCR.
• After the researchers controlled for confounding factors, those with social frailty had an increased risk for MCR compared with the normal group (pooled sample: hazard ratio [HR], 1.57; 95% CI, 1.34-1.84; P < .001).
• Each additional unfavorable social item was associated with an increased risk for MCR (pooled sample: HR, 1.32; 95% CI, 1.22-1.43; P < .001).
• Results of stratified analyses across subgroups suggested individuals with social frailty had a significantly higher risk for incident MCR than that of those without social frailty, regardless of socioeconomic status, lifestyle factors, chronic diseases, and mental health.

IN PRACTICE:

The findings suggest assessing social frailty using simple questions “is an efficient tool for detecting older individuals with a high risk of MCR,” the authors wrote. They noted that the addition of such a tool in clinical practice may facilitate “timely implementation of prevention strategies.”

SOURCE:

The research was led by Hui Zhang, Human Phenome Institute, Zhangjiang Fudan International Innovation Centre, Fudan University, Shanghai, China. It was published online on January 29, 2024, in Alzheimer’s & Dementia.

LIMITATIONS:

The study was observational, so the association between social frailty and MCR is merely correlational. Due to the lack of genetic information in NHATS data, researchers didn’t evaluate the effect of genetic factors such as apolipoprotein E on the association between social frailty and MCR. Social frailty was assessed at a single time point. In addition, the researchers were unable examine the time sequence between social frailty and MCR and so could not determine the cause of this association.

DISCLOSURES:

The study was supported by the National Natural Science Foundation of China-Youth Science Fund, Shanghai Rising-Star Program, Shanghai Municipal Health Commission and Key Discipline Construction Project of Pudong Health, and Family Planning Commission of Shanghai. The authors reported no relevant conflicts of interest.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Patients with heart failure (HF) and depression who receive psychotherapy have the same (almost 50% reduction) in depressive symptoms as those treated with pharmacotherapy, show more improvement in physical-related quality of life, and are less likely to visit emergency departments (EDs), a comparative trial of these interventions found.

METHODOLOGY:

• The study included 416 patients with HF and a confirmed depressive disorder from the Cedars-Sinai Health System, with a mean age of 60.71 years, including nearly 42% women and 30% Black individuals, who were randomized to receive one of two evidence-based treatments for depression in HF: Antidepressant medication management (MEDS) or behavioral activation (BA) psychotherapy. BA therapy promotes engaging in pleasurable and rewarding activities without delving into complex cognitive domains explored in cognitive behavioral therapy, another psychotherapy type.
• All patients received 12 weekly sessions delivered via video or telephone, followed by monthly sessions for 3 months, and were then contacted as needed for an additional 6 months.
• The primary outcome was depressive symptom severity at 6 months, measured by the Patient Health Questionnaire 9-Item (PHQ-9), and secondary outcomes included three measures of health-related quality of life (HRQOL) — caregiver burden, morbidity, and mortality — collected at 3, 6, and 12 months.
• Physical and mental HRQOL were measured with the 12-Item Short-Form Medical Outcomes Study (SF-12), HF-specific HRQOL with the 23-item patient-reported Kansas City Cardiomyopathy Questionnaire, caregiver burden with the 26-item Caregiver Burden Questionnaire for HF, morbidity by ED visits, hospital readmissions, and days hospitalized, and mortality data came from medical records and family or caregiver reports, with survival assessed using Kaplan-Meier plots at 3, 6, and 12 months.
• Covariates included age, sex, race, ethnicity, marital status, employment, education, insurance type, recruitment site (inpatient or outpatient), ejection fraction (preserved or reduced), New York Heart Association class, medical history, and medications.

TAKEAWAY:

• Depressive symptom severity was reduced at 6 months by nearly 50% for both BA (mean PHQ-9 score, 7.53; P vs baseline < .001) and MEDS (mean PHQ-9 score, 8.09; P vs baseline < .001) participants, with reductions persisting at 12 months and no significant difference between groups.
• Compared with MEDS recipients, those who received BA had slightly higher improvement in physical HRQOL at 6 months (multivariable mean difference without imputation, 2.13; 95% CI, 0.06-4.20; P = .04), but there were no statistically significant differences between groups in mental HRQOL, HF-specific HRQOL, or caregiver burden at 3, 6, or 12 months.
• Patients who received BA were significantly less likely than those in the MEDS group to have ED visits and spent fewer days in hospital at 3, 6, and 12 months, but there was no significant difference in number of hospital readmissions or in mortality at 3, 6, or 12 months.

IN PRACTICE:

“Our findings of comparable primary effects between BA and MEDS suggest both options are effective and that personal preferences, patient values, and availability of services could inform decisions,” the authors wrote. They noted BA has no pharmacological adverse effects but requires more engagement than drug therapy and might be less accessible.

SOURCE:

The study was conducted by Waguih William IsHak, MD, Department of Psychiatry and Behavioral Neurosciences, Cedars-Sinai Medical Center, Los Angeles, and others. It was published online on January 17, 2024, in JAMA Network Open.

LIMITATIONS:

As the study had no control group, such as a waiting list, it was impossible to draw conclusions about the natural course of depressive symptoms in HF. However, the authors noted improvements were sustained at 12 months despite substantially diminished contact with intervention teams after 6 months. Researchers were unable to collect data for ED visits, readmissions, and hospital stays outside of California and didn’t assess treatment preference at enrollment, which could have helped inform the association with outcomes and adherence.

DISCLOSURES:

The study was funded by the Patient-Centered Outcome Research Institute, paid to Cedars-Sinai Medical Center. Dr. IsHak reported receiving royalties from Springer Nature and Cambridge University Press. No other disclosures were reported.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Patients with heart failure (HF) and depression who receive psychotherapy have the same (almost 50% reduction) in depressive symptoms as those treated with pharmacotherapy, show more improvement in physical-related quality of life, and are less likely to visit emergency departments (EDs), a comparative trial of these interventions found.

METHODOLOGY:

• The study included 416 patients with HF and a confirmed depressive disorder from the Cedars-Sinai Health System, with a mean age of 60.71 years, including nearly 42% women and 30% Black individuals, who were randomized to receive one of two evidence-based treatments for depression in HF: Antidepressant medication management (MEDS) or behavioral activation (BA) psychotherapy. BA therapy promotes engaging in pleasurable and rewarding activities without delving into complex cognitive domains explored in cognitive behavioral therapy, another psychotherapy type.
• All patients received 12 weekly sessions delivered via video or telephone, followed by monthly sessions for 3 months, and were then contacted as needed for an additional 6 months.
• The primary outcome was depressive symptom severity at 6 months, measured by the Patient Health Questionnaire 9-Item (PHQ-9), and secondary outcomes included three measures of health-related quality of life (HRQOL) — caregiver burden, morbidity, and mortality — collected at 3, 6, and 12 months.
• Physical and mental HRQOL were measured with the 12-Item Short-Form Medical Outcomes Study (SF-12), HF-specific HRQOL with the 23-item patient-reported Kansas City Cardiomyopathy Questionnaire, caregiver burden with the 26-item Caregiver Burden Questionnaire for HF, morbidity by ED visits, hospital readmissions, and days hospitalized, and mortality data came from medical records and family or caregiver reports, with survival assessed using Kaplan-Meier plots at 3, 6, and 12 months.
• Covariates included age, sex, race, ethnicity, marital status, employment, education, insurance type, recruitment site (inpatient or outpatient), ejection fraction (preserved or reduced), New York Heart Association class, medical history, and medications.

TAKEAWAY:

• Depressive symptom severity was reduced at 6 months by nearly 50% for both BA (mean PHQ-9 score, 7.53; P vs baseline < .001) and MEDS (mean PHQ-9 score, 8.09; P vs baseline < .001) participants, with reductions persisting at 12 months and no significant difference between groups.
• Compared with MEDS recipients, those who received BA had slightly higher improvement in physical HRQOL at 6 months (multivariable mean difference without imputation, 2.13; 95% CI, 0.06-4.20; P = .04), but there were no statistically significant differences between groups in mental HRQOL, HF-specific HRQOL, or caregiver burden at 3, 6, or 12 months.
• Patients who received BA were significantly less likely than those in the MEDS group to have ED visits and spent fewer days in hospital at 3, 6, and 12 months, but there was no significant difference in number of hospital readmissions or in mortality at 3, 6, or 12 months.

IN PRACTICE:

“Our findings of comparable primary effects between BA and MEDS suggest both options are effective and that personal preferences, patient values, and availability of services could inform decisions,” the authors wrote. They noted BA has no pharmacological adverse effects but requires more engagement than drug therapy and might be less accessible.

SOURCE:

The study was conducted by Waguih William IsHak, MD, Department of Psychiatry and Behavioral Neurosciences, Cedars-Sinai Medical Center, Los Angeles, and others. It was published online on January 17, 2024, in JAMA Network Open.

LIMITATIONS:

As the study had no control group, such as a waiting list, it was impossible to draw conclusions about the natural course of depressive symptoms in HF. However, the authors noted improvements were sustained at 12 months despite substantially diminished contact with intervention teams after 6 months. Researchers were unable to collect data for ED visits, readmissions, and hospital stays outside of California and didn’t assess treatment preference at enrollment, which could have helped inform the association with outcomes and adherence.

DISCLOSURES:

The study was funded by the Patient-Centered Outcome Research Institute, paid to Cedars-Sinai Medical Center. Dr. IsHak reported receiving royalties from Springer Nature and Cambridge University Press. No other disclosures were reported.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Patients with heart failure (HF) and depression who receive psychotherapy have the same (almost 50% reduction) in depressive symptoms as those treated with pharmacotherapy, show more improvement in physical-related quality of life, and are less likely to visit emergency departments (EDs), a comparative trial of these interventions found.

METHODOLOGY:

• The study included 416 patients with HF and a confirmed depressive disorder from the Cedars-Sinai Health System, with a mean age of 60.71 years, including nearly 42% women and 30% Black individuals, who were randomized to receive one of two evidence-based treatments for depression in HF: Antidepressant medication management (MEDS) or behavioral activation (BA) psychotherapy. BA therapy promotes engaging in pleasurable and rewarding activities without delving into complex cognitive domains explored in cognitive behavioral therapy, another psychotherapy type.
• All patients received 12 weekly sessions delivered via video or telephone, followed by monthly sessions for 3 months, and were then contacted as needed for an additional 6 months.
• The primary outcome was depressive symptom severity at 6 months, measured by the Patient Health Questionnaire 9-Item (PHQ-9), and secondary outcomes included three measures of health-related quality of life (HRQOL) — caregiver burden, morbidity, and mortality — collected at 3, 6, and 12 months.
• Physical and mental HRQOL were measured with the 12-Item Short-Form Medical Outcomes Study (SF-12), HF-specific HRQOL with the 23-item patient-reported Kansas City Cardiomyopathy Questionnaire, caregiver burden with the 26-item Caregiver Burden Questionnaire for HF, morbidity by ED visits, hospital readmissions, and days hospitalized, and mortality data came from medical records and family or caregiver reports, with survival assessed using Kaplan-Meier plots at 3, 6, and 12 months.
• Covariates included age, sex, race, ethnicity, marital status, employment, education, insurance type, recruitment site (inpatient or outpatient), ejection fraction (preserved or reduced), New York Heart Association class, medical history, and medications.

TAKEAWAY:

• Depressive symptom severity was reduced at 6 months by nearly 50% for both BA (mean PHQ-9 score, 7.53; P vs baseline < .001) and MEDS (mean PHQ-9 score, 8.09; P vs baseline < .001) participants, with reductions persisting at 12 months and no significant difference between groups.
• Compared with MEDS recipients, those who received BA had slightly higher improvement in physical HRQOL at 6 months (multivariable mean difference without imputation, 2.13; 95% CI, 0.06-4.20; P = .04), but there were no statistically significant differences between groups in mental HRQOL, HF-specific HRQOL, or caregiver burden at 3, 6, or 12 months.
• Patients who received BA were significantly less likely than those in the MEDS group to have ED visits and spent fewer days in hospital at 3, 6, and 12 months, but there was no significant difference in number of hospital readmissions or in mortality at 3, 6, or 12 months.

IN PRACTICE:

“Our findings of comparable primary effects between BA and MEDS suggest both options are effective and that personal preferences, patient values, and availability of services could inform decisions,” the authors wrote. They noted BA has no pharmacological adverse effects but requires more engagement than drug therapy and might be less accessible.

SOURCE:

The study was conducted by Waguih William IsHak, MD, Department of Psychiatry and Behavioral Neurosciences, Cedars-Sinai Medical Center, Los Angeles, and others. It was published online on January 17, 2024, in JAMA Network Open.

LIMITATIONS:

As the study had no control group, such as a waiting list, it was impossible to draw conclusions about the natural course of depressive symptoms in HF. However, the authors noted improvements were sustained at 12 months despite substantially diminished contact with intervention teams after 6 months. Researchers were unable to collect data for ED visits, readmissions, and hospital stays outside of California and didn’t assess treatment preference at enrollment, which could have helped inform the association with outcomes and adherence.

DISCLOSURES:

The study was funded by the Patient-Centered Outcome Research Institute, paid to Cedars-Sinai Medical Center. Dr. IsHak reported receiving royalties from Springer Nature and Cambridge University Press. No other disclosures were reported.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Deaths caused by both substance use (SU) and cardiovascular disease (CVD) increased substantially in the United States between 1999 and 2019, with the most pronounced rise among women, American Indians, younger people, rural residents, and users of cannabis and psychostimulants, results of new research suggest.

METHODOLOGY:

• From the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) database and using International Classification of Diseases (ICD) codes, researchers collected data on deaths within the United States where both SU and CVD (SU+CVD) were a contributing or an underlying cause and gathered information on location of death (medical facility, home, hospice, nursing home/long-term care facility), demographics (sex, race/ethnicity, age), and region (urban-rural, state).
• Researchers determined crude and age-adjusted mortality rates (AAMRs) per 100,000 population, identified trends in AAMR using annual percent change (APC) and calculated the weighted average of APCs (AAPCs).
• Between 1999 and 2019, there were 636,572 deaths related to CVD+SU, 75.6% of which were among men and 70.6% among non-Hispanic White individuals, with 65% related to alcohol, and where location of death was available, 47.7% occurred in medical facilities.

TAKEAWAY:

• The overall SU+CVD-related AAMR from 1999 to 2019 was 14.3 (95% CI, 14.3-14.3) per 100,000 individuals, with the rate being higher in men (22.5) than in women (6.8) and highest in American Indians or Alaska Natives (37.7) compared with other races/ethnicities.
• Rural areas had higher SU+CVD-related AAMR (15.2; 95% CI, 15.1-15.3) than urban areas, with the District of Columbia having the highest AAMR geographically (25.4), individuals aged 55-69 years having the highest rate agewise (25.1), and alcohol accounting for the highest rate (9.09) among substance types.
• Temporal trends show that the overall SU+CVD-related AAMR increased from 9.9 in 1999 to 21.4 in 2019, a rate that started accelerating in 2012, with an AAPC of 4.0% (95% CI, 3.7-4.3); increases were across all ethnicities and age groups and were particularly pronounced among women (4.8%; 95% CI, 4.5-5.1).
• Cannabis had the highest AAPC of all substances (12.7%), but stimulants had an APC of 21.4 (95% CI, 20.0-22.8) from 2009 to 2019, a period during which stimulants were the fastest-growing substance abuse category.

IN PRACTICE:

These new results identify high-risk groups, which “is crucial for prioritizing preventive measures aiming to reduce substance use and cardiovascular disease-related mortality in these populations,” the researchers wrote.

SOURCE:

Abdul Mannan Khan Minhas, MD, Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi, and Jakrin Kewcharoen, MD, Division of Cardiology, Loma Linda University Medical Center, Loma Linda, California, were co-first authors of the study, which was published online in the Journal of the American Heart Association.

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

TOPLINE:

Deaths caused by both substance use (SU) and cardiovascular disease (CVD) increased substantially in the United States between 1999 and 2019, with the most pronounced rise among women, American Indians, younger people, rural residents, and users of cannabis and psychostimulants, results of new research suggest.

METHODOLOGY:

• From the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) database and using International Classification of Diseases (ICD) codes, researchers collected data on deaths within the United States where both SU and CVD (SU+CVD) were a contributing or an underlying cause and gathered information on location of death (medical facility, home, hospice, nursing home/long-term care facility), demographics (sex, race/ethnicity, age), and region (urban-rural, state).
• Researchers determined crude and age-adjusted mortality rates (AAMRs) per 100,000 population, identified trends in AAMR using annual percent change (APC) and calculated the weighted average of APCs (AAPCs).
• Between 1999 and 2019, there were 636,572 deaths related to CVD+SU, 75.6% of which were among men and 70.6% among non-Hispanic White individuals, with 65% related to alcohol, and where location of death was available, 47.7% occurred in medical facilities.

TAKEAWAY:

• The overall SU+CVD-related AAMR from 1999 to 2019 was 14.3 (95% CI, 14.3-14.3) per 100,000 individuals, with the rate being higher in men (22.5) than in women (6.8) and highest in American Indians or Alaska Natives (37.7) compared with other races/ethnicities.
• Rural areas had higher SU+CVD-related AAMR (15.2; 95% CI, 15.1-15.3) than urban areas, with the District of Columbia having the highest AAMR geographically (25.4), individuals aged 55-69 years having the highest rate agewise (25.1), and alcohol accounting for the highest rate (9.09) among substance types.
• Temporal trends show that the overall SU+CVD-related AAMR increased from 9.9 in 1999 to 21.4 in 2019, a rate that started accelerating in 2012, with an AAPC of 4.0% (95% CI, 3.7-4.3); increases were across all ethnicities and age groups and were particularly pronounced among women (4.8%; 95% CI, 4.5-5.1).
• Cannabis had the highest AAPC of all substances (12.7%), but stimulants had an APC of 21.4 (95% CI, 20.0-22.8) from 2009 to 2019, a period during which stimulants were the fastest-growing substance abuse category.

IN PRACTICE:

These new results identify high-risk groups, which “is crucial for prioritizing preventive measures aiming to reduce substance use and cardiovascular disease-related mortality in these populations,” the researchers wrote.

SOURCE:

Abdul Mannan Khan Minhas, MD, Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi, and Jakrin Kewcharoen, MD, Division of Cardiology, Loma Linda University Medical Center, Loma Linda, California, were co-first authors of the study, which was published online in the Journal of the American Heart Association.

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

TOPLINE:

Deaths caused by both substance use (SU) and cardiovascular disease (CVD) increased substantially in the United States between 1999 and 2019, with the most pronounced rise among women, American Indians, younger people, rural residents, and users of cannabis and psychostimulants, results of new research suggest.

METHODOLOGY:

• From the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) database and using International Classification of Diseases (ICD) codes, researchers collected data on deaths within the United States where both SU and CVD (SU+CVD) were a contributing or an underlying cause and gathered information on location of death (medical facility, home, hospice, nursing home/long-term care facility), demographics (sex, race/ethnicity, age), and region (urban-rural, state).
• Researchers determined crude and age-adjusted mortality rates (AAMRs) per 100,000 population, identified trends in AAMR using annual percent change (APC) and calculated the weighted average of APCs (AAPCs).
• Between 1999 and 2019, there were 636,572 deaths related to CVD+SU, 75.6% of which were among men and 70.6% among non-Hispanic White individuals, with 65% related to alcohol, and where location of death was available, 47.7% occurred in medical facilities.

TAKEAWAY:

• The overall SU+CVD-related AAMR from 1999 to 2019 was 14.3 (95% CI, 14.3-14.3) per 100,000 individuals, with the rate being higher in men (22.5) than in women (6.8) and highest in American Indians or Alaska Natives (37.7) compared with other races/ethnicities.
• Rural areas had higher SU+CVD-related AAMR (15.2; 95% CI, 15.1-15.3) than urban areas, with the District of Columbia having the highest AAMR geographically (25.4), individuals aged 55-69 years having the highest rate agewise (25.1), and alcohol accounting for the highest rate (9.09) among substance types.
• Temporal trends show that the overall SU+CVD-related AAMR increased from 9.9 in 1999 to 21.4 in 2019, a rate that started accelerating in 2012, with an AAPC of 4.0% (95% CI, 3.7-4.3); increases were across all ethnicities and age groups and were particularly pronounced among women (4.8%; 95% CI, 4.5-5.1).
• Cannabis had the highest AAPC of all substances (12.7%), but stimulants had an APC of 21.4 (95% CI, 20.0-22.8) from 2009 to 2019, a period during which stimulants were the fastest-growing substance abuse category.

IN PRACTICE:

These new results identify high-risk groups, which “is crucial for prioritizing preventive measures aiming to reduce substance use and cardiovascular disease-related mortality in these populations,” the researchers wrote.

SOURCE:

Abdul Mannan Khan Minhas, MD, Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi, and Jakrin Kewcharoen, MD, Division of Cardiology, Loma Linda University Medical Center, Loma Linda, California, were co-first authors of the study, which was published online in the Journal of the American Heart Association.

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