Differential Effect of Low-Dose Aspirin for Primary Prevention of Atherosclerotic Events in Diabetes Management: A subanalysis of the JPAD trial

OBJECTIVE: Recent reports showed that low-dose aspirin was ineffective in the primary prevention of cardiovascular events in diabetic patients overall. We hypothesized that low-dose aspirin would be beneficial in patients receiving insulin therapy, as a high-risk group. RESEARCH DESIGN AND METHODS: This study is a subanalysis of the Japanese Primary Prevention of Atherosclerosis With Aspirin for Diabetes (JPAD) trial—a randomized, controlled, open-label trial. We randomly assigned 2,539 patients with type 2 diabetes and no previous cardiovascular disease to the low-dose aspirin group (81 or 100 mg daily) or to the no-aspirin group. The median follow-up period was 4.4 years. We investigated the effect of low-dose aspirin on preventing atherosclerotic events in groups receiving different diabetes management. RESULTS: At baseline, 326 patients were treated with insulin, 1,750 with oral hypoglycemic agents (OHAs), and 463 with diet alone. The insulin group had the longest history of diabetes, the worst glycemic control, and the highest prevalence of diabetic microangiopathies. The diet-alone group had the opposite characteristics. The incidence of atherosclerotic events was 26.6, 14.6, and 10.4 cases per 1,000 person-years in the insulin, OHA, and diet-alone groups, respectively. In the insulin and OHA groups, low-dose aspirin did not affect atherosclerotic events (insulin: hazard ratio [HR] 1.19 [95% CI 0.60−2.40]; OHA: HR 0.84 [0.57−1.24]). In the diet-alone group, low-dose aspirin significantly reduced atherosclerotic events, despite the lowest event rates (HR 0.21 [0.05−0.64]). CONCLUSIONS: Low-dose aspirin reduced atherosclerotic events predominantly in the diet-alone group and not in the insulin or OHA groups.