Mixed results with low-dose aspirin as primary prevention of vascular events in type 2 diabetes

Low-dose aspirin did not result in a significant reduction in first atherosclerotic events in patients with type 2 diabetes, reports Hisao Ogawa, MD, PhD (pictured), lead investigator of the Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes (JPAD) trial.

Aspirin is recommended for the primary prevention of vascular events in patients with type 2 diabetes by the American Heart Association and the American Diabetes Association, among others. Previous trials of aspirin for primary prevention of atherosclerotic events were not conducted specifically in patients with type 2 diabetes, but did contain patients with type 2 diabetes, notes Dr. Ogawa.

JPAD was conducted in 2,539 patients aged 30 to 85 years with type 2 diabetes. They were randomized to 81 or 100 mg of aspirin daily or no aspirin in an open-label fashion. The study was conducted at 183 institutions in Japan.

After a median follow-up of 4.37 years, there were 68 such events in the aspirin group and 86 in the non-aspirin group, a 20% difference that failed to achieve statistical significance (p=.2). Among the 1,363 patients 65 years or older, aspirin was associated with a 32% reduction (p=.047) in the risk of the primary endpoint.

The incidence of fatal coronary and cerebrovascular events (a secondary endpoint) was significantly lower, by 90% (p=.004), in aspirin-treated patients, says Dr. Ogawa, department of cardiovascular medicine, Graduate School of Medical Studies, Kumamoto University, Kumamoto, Japan.

There was no difference between the aspirin and non-aspirin groups for the composite of hemorrhagic stroke and severe gastrointestinal bleeding (10 events vs. 7 events).

The findings should be interpreted in the context of the low incidence of atherosclerotic disease in Japan, says Dr. Ogawa, who notes that because of the low event rate in JPAD, the study may have been underpowered to demonstrate a significant effect of aspirin on the primary endpoint. The finding of a favorable effect of aspirin on the secondary endpoint of fatal cardiovascular events in JPAD replicates the finding observed in the Primary Prevention Project trial, he adds, although such an effect was absent in two other trials-the Hypertension Optimal Treatment study and the Women’s Health Study.