Aspirin for Prevention of Cardiovascular Events in a General Population Screened for a Low Ankle Brachial Index: A Randomized Controlled Trial

Abstract

Conclusion: Patients with asymptomatic vascular disease identified by a low ankle-brachial index (ABI) do not have a reduction in vascular events with daily aspirin administration. Summary: A low ABI is a marker of systemic atherosclerosis and is associated with coexisting cerebral vascular and coronary disease. In men with a low ABI (<0.9), there is a 27% risk over 10 years of a major coronary event vs 9% in those with ABIs between 1.11 and 1.4; for women, the figures are 19% and 9% (Fowkes FG, JAMA 2008;300:197-208). It is controversial whether screening ABIs should be performed in asymptomatic patients because there is minimal evidence for an effective intervention in asymptomatic individuals with a low ABI (US Preventative Services Task Force, AHRQ, Publication No. 05-0583-A-EF. http//www.ahrg.gov/clinic.uspstf05/pad/padrs.htm). The authors sought to determine the effectiveness of aspirin in preventing cardiovascular events in otherwise asymptomatic individuals found to have a low ABI. This was an intention-to-treat, double-blind, randomized, controlled trial conducted between April 1998 and October 2008 involving 28,980 men and women aged 50 to 75 years. All were free of clinically evident vascular disease. Patients wre recruited from a community health registry in Scotland and had ABI screening tests, and 3350 were identified with a low ABI (≤0.095) and entered the trial. Patients were randomized to daily 100 mg enteric-coated aspirin or placebo. The primary end point was a composite end point of an initial fatal or nonfatal coronary event, a revascularization procedure, or stroke. Secondary end points were a composite of all primary end point events plus new intermittent claudication or transient ischemic attack. An additional secondary end point was all cause mortality. Mean follow-up was 8.2 ± 1.6 years. During follow-up, 357 of the 3350 study participants had a primary end point event (13.5/1,000 person-years; 95% CI, 12.2-15.0). There was no statistical difference between the incidence of the primary end point between groups, consisting of 13.7 events/1000 person years in the aspirin group vs 13.3 in the placebo group (HR, 1.03; 95% CI, 0.84-1.7). The secondary end point of any vascular event occurred in 578 participants (22.8/1,000 person years; 95% CI, 21.0-24.8). There was no statistical difference between the aspirin (22.8 events/1000 person-years) and placebo (22.9 events/1000 person years) groups (HR, 1.0; 95% CI, 0.85-1.17). Similarly there was no difference in all cause mortality between groups (176 vs 186 deaths, respectively; HR, 0.95; 95% CI, 0.77-1.16). Major hemorrhage requiring admission to the hospital occurred in 34 subjects (2.5/1,000 person years in the aspirin group and 1.5/1,000 person years in the placebo group; HR, 1.71; 95% CI, 0.99-2.97). Comment: The trial suggested ABI screening in individuals free of clinical cardiovascular disease is unlikely to be beneficial if the intervention for a low ABI is prophylactic low-dose aspirin. It does not rule out the possibility that other therapies, such as statins or perhaps different antiplatelet agents with less hemorrhagic risk, might confer benefit. In practical terms, the results indicate that somewhere between 500 and 600 people would need to be screened with ABI studies and treated with aspirin to prevent one major cardiovascular event over 8 years. It seems difficult to justify the resources required for such massive screening with such little return.