Aspirin's effect in primary prevention of cardiovascular disease appears weak, may be sex-specific

Aspirin's efficacy in preventing first cardiovascular events in patients with diabetes is equivocal, according to a new meta-analysis of prospective, randomized clinical trials. The effect of aspirin in this patient population may be sex-specific, says Antonio Nicolucci, MD, Department of Clinical Pharmacology and Epidemiology, Consorzio Mario Negri Sud, Via Nazionale, Italy.

As such, better stratification of those patients with diabetes who may benefit from aspirin as primary prevention is needed, he says.

Various guidelines for the primary prevention of cardiovascular disease in patients with diabetes are inconsistent in their recommendations for the use of aspirin. For example, the American Heart Association/American Diabetes Association guidelines recommend its use in all patients with diabetes older than 40 years who have cardiovascular risk factors, whereas the European Society of Cardiology recommends it in diabetics only for stroke prevention, and the Canadian Diabetes Association states that no evidence exists for aspirin use for primary prevention in diabetes and that its use should be left to individual clinical judgment.

Six randomized, controlled trials that compared aspirin and placebo (or no aspirin) in a prospective manner in patients with diabetes who were free of cardiovascular disease at baseline, and in which outcomes for major cardiovascular events or mortality was reported, were included in the analysis. The six studies enrolled a total of 10,117 patients.

The effect estimates were pooled using a random-effect model, and heterogeneity was assessed.

Aspirin was associated with small but nonsignificant reductions in the incidence of major cardiovascular events (9% relative risk reduction [RRR]; p=0.07), cardiovascular mortality (6% RRR; p=0.6), and overall mortality (7% RRR; p=0.25).

Significant heterogeneity between trials was observed in aspirin's effect on myocardial infarction (MI), which could be explained mostly by a difference in the effect by sex, says Dr. Nicolucci. Aspirin was associated with a significant 43% RRR (p=0.03) in the incidence of first MI in men, whereas there was no effect in women (7% relative excess; p=0.71).

The opposite was true in stroke: aspirin increased the risk by a nonsignificant 11% in men (p=0.61) but was associated with a trend toward a 25% RRR in women (p=0.43). Overall, aspirin was associated with a nonsignificant 18% RRR (p=0.07) in stroke.

In weighing the overall merit of aspirin use for primary prevention in patients with diabetes, Dr. Nicolucci calculated that 1,000 patients would need to be treated for 1 year to prevent 1 to 2 events. "Unfortunately, the excess risk of major bleeding is in the same range-1 to 2 events per year," he says. "In individuals with a low risk of cardiovascular events (<2% per year) and in those with a high risk of bleeding complications, such as elderly patients, the risks can outweigh the benefits."

Ongoing randomized, controlled trials will help clarify whether aspirin confers additional benefits on top of current strategies to reduce cardiovascular risk.