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Cardiovascular Prevention With Aspirin in Type 2 Diabetes
Study Questions:
What is the long-term efficacy and safety of low-dose aspirin for primary prevention of cardiovascular (CV) events in patients with type 2 diabetes?
Methods:
The JPAD (Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes) trial was a randomized, open-label, standard-care controlled trial examining whether low-dose aspirin affected CV events in 2,539 Japanese patients with type 2 diabetes and without pre-existing CV disease (CVD). Patients were randomly allocated to receive aspirin (81 mg or 100 mg daily, aspirin group) or no aspirin (no-aspirin group) in the JPAD trial. After the trial ended in 2008, the investigators followed the patients until 2015, with no attempt to change the previously assigned therapy. Primary endpoints were CV events, including sudden death, fatal or nonfatal coronary artery disease, fatal or nonfatal stroke, and peripheral vascular disease. For the safety analysis, hemorrhagic events, consisting of gastrointestinal bleeding, hemorrhagic stroke, and bleeding from any other sites, were also analyzed. The primary analysis was conducted for CV events among patients who retained their original allocation (a per-protocol cohort). Analyses on an intention-to-treat cohort were conducted for hemorrhagic events and statistical sensitivity.
Results:
The median follow-up period was 10.3 years, 1,621 (64%) patients were followed throughout the study, and 2,160 (85%) patients retained their original allocation. Low-dose aspirin did not reduce CV events in the per-protocol cohort (hazard ratio [HR], 1.14; 95% confidence interval [CI], 0.91-1.42). Multivariable Cox proportional hazard model adjusted for age, sex, glycemic control, kidney function, smoking status, hypertension, and dyslipidemia showed similar results (HR, 1.04; 95% CI, 0.83-1.30), with no heterogeneity of efficacy in subgroup analyses stratified by each of these factors (interaction P-values all > 0.05). Sensitivity analyses on the intention-to-treat cohort yielded consistent results (HR, 1.01; 95% CI, 0.82-1.25). Gastrointestinal bleeding occurred in 25 (2%) patients in the aspirin group and 12 (0.9%) in the no-aspirin group (p = 0.03), though the incidence of hemorrhagic stroke was not different between the groups.
Conclusions:
The authors concluded that low-dose aspirin did not affect the risk for CV events, but increased risk for gastrointestinal bleeding in patients with type 2 diabetes in a primary prevention setting.
Perspective:
This study reports that long-term therapy with low-dose aspirin is not associated with lower CV events in Japanese patients with type 2 diabetes in a primary prevention setting. Furthermore, low-dose aspirin therapy was associated with and significantly increased incidence of gastrointestinal bleeding. These findings support the American College of Cardiology expert consensus document, which states that aspirin should not be recommended for CVD prevention for adults with diabetes at low CVD risk (men under age 50 years and women under 60 years with no major additional CVD risk factors; 10-year CVD risk under 5%), as the potential adverse effects from bleeding offset the potential benefits.
Keywords: Aspirin, Cardiovascular Diseases, Death, Sudden, Diabetes Mellitus, Type 2, Gastrointestinal Hemorrhage, Coronary Artery Disease, Metabolic Syndrome, Peripheral Vascular Diseases, Primary Prevention, Risk Factors, Stroke, AHA Annual Scientific Sessions, AHA16
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