Cardiology Express Report

Publication date: 2003-09-05

The Safety and Efficacy of Low-dose Aspirin for the Prevention of Cardiovascular Disease

This report was reviewed for medical and scientific accuracy by Robert J. Hilkert, MD, FACC, Associate Professor of Medicine, Associate Fellowship Director, Cardiovascular Diseases, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick, New Jersey

Introduction

Cardiovascular disease (CVD) is still the leading cause of death in the United States and most developed countries, accounting for nearly 960,000 deaths annually in the United States alone.¹ This is 40.1% of all deaths or one of every 2.5 deaths, a staggering statistic. Along with lifestyle and medical management, the use of prophylactic aspirin in both acute and chronic care has become an integral component as the preferred treatment option in preventing CVD. Since ISIS-2,² one of the first clinical trials to demonstrate that aspirin alone can reduce mortality in acute myocardial infarction patients, aspirin has become one of the most important agents for preventing the adverse outcomes of CVD and has been the subject of hundreds of clinical studies and meta-analyses.

Despite its proven efficacy for primary and secondary prevention of CVD, prophylactic aspirin is underutilized in patients with CVD. In 2000, Stafford reported that although aspirin use in patients with coronary heart disease increased from 5.0% in 1980 to 26.2% in 1996,³ its use remains suboptimal. Moreover, despite its extensive clinical investigation, the critically important issue of the optimal dose of aspirin for primary prevention of CVD continues to be the subject of debate. The American Diabetes Association treatment guidelines on aspirin use in diabetes concludes that a 75 mg dose of aspirin is just as effective as higher doses of aspirin in inhibiting thromboxane synthesis and recommends aspirin therapy for primary prevention in diabetic patients.⁴ The American Heart Association recommends a daily dose of 75 to 160 mg of aspirin stating this dose is as effective as higher doses and this dose should be used in patients with a 10-year risk of coronary heart disease of ≥10%⁵ using the Framingham risk algorithm⁶. Thus, treatment guidelines would suggest the optimal dose of aspirin for prevention of CVD would be between 75 and 160 mg [81 to 162 mg in the United States].

This Cardiology Express Report will review the latest evidence-based medicine on prophylactic low-dose aspirin use highlighted during a recently held meeting of nationally, recognized cardiologists brought together to discuss guidelines for the use of aspirin in cardioprotective therapy.⁷

Efficacy Established for Low-dose Aspirin

The Antithrombotic Trialists' Collaboration (ATC) meta-analysis provided critical information about efficacy according to aspirin dose.⁸ The ATC meta-analysis determined the effects of antiplatelet therapy on serious vascular events (non-fatal myocardial infarction, non-fatal stroke, or vascular death) among patients at high risk of occlusive vascular events. The meta-analysis reviewed 287 clinical studies involving 135,000 patients in comparisons of antiplatelet therapy versus control and 77,000 patients in comparisons of different antiplatelet regimens.

The ATC meta-analysis found that antiplatelet therapy reduced the risk of any serious vascular event by approximately 25%; non-fatal myocardial infarction was reduced by approximately 33%, non-fatal stroke by 25%, and vascular mortality by approximately 17%. Among the trials analyzed, aspirin was the most widely studied antiplatelet medication. Also, several dose ranges of aspirin were used throughout the trials, giving investigators an opportunity to compare antiplatelet efficacy at more specific doses of aspirin.

Three trials including 3,570 patients directly compared daily aspirin doses of <75 mg to ≥75 mg. Overall, there was no significant difference in efficacy between the aspirin regimens (Table 1). However, a