Patients with low ankle-brachial index did not benefit from aspirin therapy

Asymptomatic patients at increased risk for peripheral arterial disease based on ankle-brachial index screening who were assigned to once-daily aspirin therapy did not experience significant reductions in vascular events compared with those not assigned to the therapy, according to findings published today online.

“Although an ABI might better define risk, a major argument against screening is lack of evidence for an effective intervention for those with a low ABI,” the researchers wrote. “Antiplatelet drugs including aspirin are effective in the secondary prevention of events of patients with known vascular disease, but aspirin may have only a modest effect as a primary prevention for healthy individuals.”

Researchers from the United Kingdom randomly assigned patients from a community health registry in central Scotland to either aspirin (100 mg; n=1,675) or placebo (n=1,675) as part of the Aspirin for Asymptomatic Atherosclerosis trial. Only those without a history of clinical CVD were enrolled. Patients were aged 50 to 75 years and had an ABI ≤0.95; 72% were women. The trial was powered to detect a 25% proportional risk reduction in events.

After the mean follow-up period of 8.2 years, rates of patients who experienced the primary endpoint of composite initial fatal or nonfatal coronary event, stroke or revascularization were similar between the two groups (13.7 per 1,000 person-years in the aspirin group vs. 13.3 per 1,000 person-years in the placebo group; HR=1.03; 95% CI, 0.84-1.27).

Findings for secondary endpoints composed of initial vascular events including angina, intermittent claudication or transient ischemic attack were similar, with no statistically significant differences between the two groups (22.8 per 1,000 person-years in the aspirin group vs. 22.9 per 1,000 person-years in the placebo group; HR=1.00; 95% CI, 0.85-1.17). Additionally, the researchers observed no differences in all-cause mortality between the two groups (176 in the aspirin group vs. 186 in the placebo group; HR=0.95; 95% CI, 0.77-1.16).

Patients in the aspirin group more frequently experienced an initial event involving major hemorrhage that required hospitalization compared with those in the placebo group (2.5 per 1,000 person-years vs. 1.5 per 1,000 person-years; HR=1.71; 95% CI, 0.99-2.97).

The researchers acknowledged that they were unable to rule out the possibility of an up to 16% risk reduction, given the HRs and 95% CIs. However, after extrapolating numbers from trial participants, they determined that between 500 and 600 people from the general population would need to be screened and prescribed aspirin to prevent a single major CV event during an eight-year period.

“It is highly questionable whether the additional resources required to screen and treat such a large number of people to prevent only a small number of events would be justified or indeed whether a larger trial to try and demonstrate such a small effect should be considered,” the researchers wrote.

The researchers acknowledged that ABI is a simple, inexpensive and noninvasive test to identify patients at risk for CVD but suggested alternative therapies without hemorrhagic risks, such as statins or more potent antiplatelet agents, for intervention in lieu of aspirin.

“The clinical benefits of aspirin therapy for patients with PAD remain unproven,” Jeffrey S. Berger, MD, of the New York University School of Medicine, wrote in an accompanying editorial, adding that they reinforce findings from another recent meta-analysis, which failed to demonstrate the benefit with aspirin therapy.

Fowkes FGR. JAMA. 2010;303:841-848.