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ANAHEIM, CALIF.Daily low-dose aspirin reduced the incidence of dementia by more than one-third in patients with type 2 diabetes mellitus in the randomized JPAD 2 study, Chisa Matsumoto, MD, reported at the American Heart Association scientific sessions.

The benefit was restricted to women with T2DM. During a median 9.7 years of follow-up, the incidence of dementia, as defined by prescription of antidementia drugs or hospitalization for dementia, was 2.7 cases per 1,000 person-years in women randomized to low-dose aspirin and 6 per 1,000 person-years in those assigned to standard care. This translated to a 60% relative risk reduction in a multivariate analysis adjusted for age, hypertension, dyslipidemia, smoking, and hemoglobin A1c level, according to Dr. Matsumoto of Hyogo (Japan) College of Medicine.

Dr. Chisa Matsumoto of Hyogo (Japan) College of Medicine
Bruce Jancin/Frontline Medical News
Dr. Chisa Matsumoto
In men with T2DM, there was no significant difference in rates of new-onset dementia between the low-dose aspirin and control groups.

JPAD 2 was a multicenter prospective cohort study of 2,536 Japanese patients with T2DM who previously participated in the open-label randomized Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes (JPAD) trial, which ran from 2002 to 2008. Patients’ average age at baseline was 64 years; they had a 7-year duration of diabetes and no history of cardiovascular disease or dementia. When JPAD ended, patients continued on in JPAD 2, with follow-up through July 2015.

 

 


In the overall JPAD 2 population, the dementia incidence rate was 3.6 per 1,000 person-years in the low-dose aspirin group compared with 4.9 per 1,000 person-years in controls, for a highly significant 35% relative risk reduction in a fully adjusted multivariate intention to treat analysis.

During follow-up, 15% of patients switched from low-dose aspirin to no aspirin or vice versa, prompting Dr. Matsumoto and her coinvestigators to perform a per protocol analysis of the data. The results were essentially the same as in the intent-to-treat analysis.

JPAD 2 was the first-ever study to evaluate the long-term efficacy of low-dose aspirin for prevention of dementia specifically in patients with T2DM, a known risk factor for dementia. Other observational and randomized controlled studies have yielded inconsistent results. For example, a recent meta-analysis of five studies with a median 6-year follow-up found an 18% relative risk reduction in onset of dementia or cognitive impairment, a difference that didn’t achieve statistical significance (J Am Geriatr Soc. 2017 Aug;65[8]:1763-8).

Some prior studies have suggested there is a sex-based difference in the risk of dementia, which prompted Dr. Matsumoto and her coinvestigators to analyze the JPAD 2 results separately in men and women.

 

 


She was quick to acknowledge that the novel JPAD 2 findings cry out for replication in other studies with larger numbers and/or longer follow-up.

Session moderator Mary Cushman, MD, declared, “I think this is really exciting and interesting.”

Dr. Mary Cushman, professor of medicine and pathology and medical director of the thrombosis and hemostasis program at the University of Vermont in Burlington.
Dr. Mary Cushman
There are quite a few Western large cohort studies examining the use of low-dose aspirin for prevention of cardiovascular events, and many of them also feature cognitive outcomes. It should be easy to find collaborators from those studies who could cull out the data on participants with type 2 diabetes in order to confirm the JPAD 2 findings, according to Dr. Cushman, professor of medicine and pathology and medical director of the thrombosis and hemostasis program at the University of Vermont in Burlington.

Asked to speculate on the mechanism for the divergent efficacy of low-dose aspirin in men and women with T2DM in JPAD 2, Dr. Matsumoto said play of chance may have had a partial role. The incidence of dementia was roughly 50% greater in the JPAD 2 women than in the men, so the study may have been underpowered to look at the dementia rate in men. But there may be a biologic mechanism at work, as well: Apolipoprotein E4, which is linked to increased risk of dementia, is believed to interact with gender, she said.

Dr. Matsumoto reported having no financial conflicts.

SOURCE: Matsumoto C. AHA scientific sessions.

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ANAHEIM, CALIF.Daily low-dose aspirin reduced the incidence of dementia by more than one-third in patients with type 2 diabetes mellitus in the randomized JPAD 2 study, Chisa Matsumoto, MD, reported at the American Heart Association scientific sessions.

The benefit was restricted to women with T2DM. During a median 9.7 years of follow-up, the incidence of dementia, as defined by prescription of antidementia drugs or hospitalization for dementia, was 2.7 cases per 1,000 person-years in women randomized to low-dose aspirin and 6 per 1,000 person-years in those assigned to standard care. This translated to a 60% relative risk reduction in a multivariate analysis adjusted for age, hypertension, dyslipidemia, smoking, and hemoglobin A1c level, according to Dr. Matsumoto of Hyogo (Japan) College of Medicine.

Dr. Chisa Matsumoto of Hyogo (Japan) College of Medicine
Bruce Jancin/Frontline Medical News
Dr. Chisa Matsumoto
In men with T2DM, there was no significant difference in rates of new-onset dementia between the low-dose aspirin and control groups.

JPAD 2 was a multicenter prospective cohort study of 2,536 Japanese patients with T2DM who previously participated in the open-label randomized Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes (JPAD) trial, which ran from 2002 to 2008. Patients’ average age at baseline was 64 years; they had a 7-year duration of diabetes and no history of cardiovascular disease or dementia. When JPAD ended, patients continued on in JPAD 2, with follow-up through July 2015.

 

 


In the overall JPAD 2 population, the dementia incidence rate was 3.6 per 1,000 person-years in the low-dose aspirin group compared with 4.9 per 1,000 person-years in controls, for a highly significant 35% relative risk reduction in a fully adjusted multivariate intention to treat analysis.

During follow-up, 15% of patients switched from low-dose aspirin to no aspirin or vice versa, prompting Dr. Matsumoto and her coinvestigators to perform a per protocol analysis of the data. The results were essentially the same as in the intent-to-treat analysis.

JPAD 2 was the first-ever study to evaluate the long-term efficacy of low-dose aspirin for prevention of dementia specifically in patients with T2DM, a known risk factor for dementia. Other observational and randomized controlled studies have yielded inconsistent results. For example, a recent meta-analysis of five studies with a median 6-year follow-up found an 18% relative risk reduction in onset of dementia or cognitive impairment, a difference that didn’t achieve statistical significance (J Am Geriatr Soc. 2017 Aug;65[8]:1763-8).

Some prior studies have suggested there is a sex-based difference in the risk of dementia, which prompted Dr. Matsumoto and her coinvestigators to analyze the JPAD 2 results separately in men and women.

 

 


She was quick to acknowledge that the novel JPAD 2 findings cry out for replication in other studies with larger numbers and/or longer follow-up.

Session moderator Mary Cushman, MD, declared, “I think this is really exciting and interesting.”

Dr. Mary Cushman, professor of medicine and pathology and medical director of the thrombosis and hemostasis program at the University of Vermont in Burlington.
Dr. Mary Cushman
There are quite a few Western large cohort studies examining the use of low-dose aspirin for prevention of cardiovascular events, and many of them also feature cognitive outcomes. It should be easy to find collaborators from those studies who could cull out the data on participants with type 2 diabetes in order to confirm the JPAD 2 findings, according to Dr. Cushman, professor of medicine and pathology and medical director of the thrombosis and hemostasis program at the University of Vermont in Burlington.

Asked to speculate on the mechanism for the divergent efficacy of low-dose aspirin in men and women with T2DM in JPAD 2, Dr. Matsumoto said play of chance may have had a partial role. The incidence of dementia was roughly 50% greater in the JPAD 2 women than in the men, so the study may have been underpowered to look at the dementia rate in men. But there may be a biologic mechanism at work, as well: Apolipoprotein E4, which is linked to increased risk of dementia, is believed to interact with gender, she said.

Dr. Matsumoto reported having no financial conflicts.

SOURCE: Matsumoto C. AHA scientific sessions.

 

ANAHEIM, CALIF.Daily low-dose aspirin reduced the incidence of dementia by more than one-third in patients with type 2 diabetes mellitus in the randomized JPAD 2 study, Chisa Matsumoto, MD, reported at the American Heart Association scientific sessions.

The benefit was restricted to women with T2DM. During a median 9.7 years of follow-up, the incidence of dementia, as defined by prescription of antidementia drugs or hospitalization for dementia, was 2.7 cases per 1,000 person-years in women randomized to low-dose aspirin and 6 per 1,000 person-years in those assigned to standard care. This translated to a 60% relative risk reduction in a multivariate analysis adjusted for age, hypertension, dyslipidemia, smoking, and hemoglobin A1c level, according to Dr. Matsumoto of Hyogo (Japan) College of Medicine.

Dr. Chisa Matsumoto of Hyogo (Japan) College of Medicine
Bruce Jancin/Frontline Medical News
Dr. Chisa Matsumoto
In men with T2DM, there was no significant difference in rates of new-onset dementia between the low-dose aspirin and control groups.

JPAD 2 was a multicenter prospective cohort study of 2,536 Japanese patients with T2DM who previously participated in the open-label randomized Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes (JPAD) trial, which ran from 2002 to 2008. Patients’ average age at baseline was 64 years; they had a 7-year duration of diabetes and no history of cardiovascular disease or dementia. When JPAD ended, patients continued on in JPAD 2, with follow-up through July 2015.

 

 


In the overall JPAD 2 population, the dementia incidence rate was 3.6 per 1,000 person-years in the low-dose aspirin group compared with 4.9 per 1,000 person-years in controls, for a highly significant 35% relative risk reduction in a fully adjusted multivariate intention to treat analysis.

During follow-up, 15% of patients switched from low-dose aspirin to no aspirin or vice versa, prompting Dr. Matsumoto and her coinvestigators to perform a per protocol analysis of the data. The results were essentially the same as in the intent-to-treat analysis.

JPAD 2 was the first-ever study to evaluate the long-term efficacy of low-dose aspirin for prevention of dementia specifically in patients with T2DM, a known risk factor for dementia. Other observational and randomized controlled studies have yielded inconsistent results. For example, a recent meta-analysis of five studies with a median 6-year follow-up found an 18% relative risk reduction in onset of dementia or cognitive impairment, a difference that didn’t achieve statistical significance (J Am Geriatr Soc. 2017 Aug;65[8]:1763-8).

Some prior studies have suggested there is a sex-based difference in the risk of dementia, which prompted Dr. Matsumoto and her coinvestigators to analyze the JPAD 2 results separately in men and women.

 

 


She was quick to acknowledge that the novel JPAD 2 findings cry out for replication in other studies with larger numbers and/or longer follow-up.

Session moderator Mary Cushman, MD, declared, “I think this is really exciting and interesting.”

Dr. Mary Cushman, professor of medicine and pathology and medical director of the thrombosis and hemostasis program at the University of Vermont in Burlington.
Dr. Mary Cushman
There are quite a few Western large cohort studies examining the use of low-dose aspirin for prevention of cardiovascular events, and many of them also feature cognitive outcomes. It should be easy to find collaborators from those studies who could cull out the data on participants with type 2 diabetes in order to confirm the JPAD 2 findings, according to Dr. Cushman, professor of medicine and pathology and medical director of the thrombosis and hemostasis program at the University of Vermont in Burlington.

Asked to speculate on the mechanism for the divergent efficacy of low-dose aspirin in men and women with T2DM in JPAD 2, Dr. Matsumoto said play of chance may have had a partial role. The incidence of dementia was roughly 50% greater in the JPAD 2 women than in the men, so the study may have been underpowered to look at the dementia rate in men. But there may be a biologic mechanism at work, as well: Apolipoprotein E4, which is linked to increased risk of dementia, is believed to interact with gender, she said.

Dr. Matsumoto reported having no financial conflicts.

SOURCE: Matsumoto C. AHA scientific sessions.

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Key clinical point: Long-term use of low-dose aspirin may protect against incident dementia in patients with type 2 diabetes mellitus.

Major finding: Daily low-dose aspirin reduced the incidence of dementia by more than one-third in patients with type 2 diabetes.

Study details: A multicenter randomized prospective cohort study of 2,536 patients with type 2 diabetes.

Disclosures: The study presenter reported having no financial conflicts.

Source: Matsumoto C. AHA scientific sessions.

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