Low-Dose Aspirin for Primary Prevention of Atherosclerotic Events in Patients with Type 2 Diabetes: A Randomized Controlled Trial

Abstract

Conclusion: Low-dose aspirin as primary prevention does not reduce the risk of cardiovascular events in patients with type 2 diabetes. Summary: In patients with previous cardiovascular events, aspirin therapy can serve as a secondary prevention strategy. Clinical guidelines also recommend patients with risk factors for coronary heart disease should take aspirin for primary prevention. However, subgroup analyses of large trials of aspirin for primary prevention have not demonstrated significant effects in patients with diabetes. Because these analyses were subgroup analyses, it is possible they were underpowered to demonstrate primary prevention of cardiovascular events with aspirin in patients with diabetes. The Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes (JPAD) Trial is reported here. The objective was to determine possible efficacy of low-dose aspirin for primary prevention of atherosclerotic events in patients with type 2 diabetes. This was a multicenter, prospective, randomized, open labeled, blinded end point trial conducted from December 2002 through April 2008 in 163 Japanese institutions. The study enrolled 2539 patients with type 2 diabetes who did not have a history of atherosclerotic disease. The median follow-up was 4.4 years. Patients in the aspirin group were treated with 81 or 100 mg daily. Primary end points included fatal or nonfatal stroke, fatal or nonfatal ischemic heart disease, and peripheral arterial disease. Secondary end points were each component of the primary end point, combinations of primary end points, and death from any cause. There were 154 atherosclerotic events comprising 68 events in the aspirin group (13.6 per 1000 person-years) and 86 events in the nonaspirin group (17.0 per 1000 person-years; hazard ratio [HR], 0.80; 95% confidence interval [CI], 0.58-1.10; P = .16). The combined end point of fatal coronary events and fatal cerebrovascular events occurred in one patient in the aspirin group and in 10 patients in the nonaspirin group (HR, 1.10; 95% CI, 0.01-0.79; P = .0037). Death from any cause occurred in 34 patients in the aspirin group and 38 patients in the nonaspirin group (HR, 0.90; 95% CI, 0.57-1.14; P = .67). There was no difference in the aspirin and nonaspirin groups for the composite of hemorrhagic stroke and significant gastrointestinal bleeding. Comment: It is becoming frustrating to demonstrate any means of decreasing atherosclerotic events in patients with diabetes. Recent trials have suggested that strictly controlling plasma glucose levels is also ineffective in reducing cardiovascular events in patients with type 2 diabetes. Because of the low event rate in this trial and that it was conducted on an entirely Japanese population, it is probably too early to conclude that aspirin is ineffective as primary preventative therapy in patients with type 2 diabetes. Evidence is accumulating to that effect, however. See also the abstract “The Prevention of Progression of Arterial Disease and Diabetes (POPADAD) Trial: Factorial Randomised Placebo Controlled Trial of Aspirin and Antioxidants in Patients with Diabetes and Asymptomatic Peripheral Arterial Disease” in this month's abstract section of Journal of Vascular Surgery.