Cardiology Express Report

Publication date: 2002-12-03

Review and Analysis of the 2002 AHA and ADA Guidelines: Utilizing Aspirin Therapy

This report was reviewed for medical and scientific accuracy by John B. Kostis, MD, John G, Detwiler Professor of Cardiology, Professor of Medicine & Pharmacology, Chairman, Department of Medicine, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, New Jersey

Editorial

Eric J. Topol, MD, Provost and Chief Academic Officer, Chairman, Department of Cardiovascular Medicine, The Cleveland Clinic Foundation, Cleveland, Ohio

If there ever were to be a year attached to a therapeutic, the year 2002 would be known as a giant step in the advances of our understanding and appreciation of aspirin's benefit. As in China, a year is denoted by a particular animal of special regard, in the field of cardiovascular medicine no therapeutic agent has had more profound an impact over the time course of decades, and especially the new findings that have become available in a matter of months.

The jump forward in aspirin can be divided into two segments—the availability of new data sets, and the transformation of major, new guidelines from professional societies and organizations.

The new data took shape from 3 major studies. First, the Antithrombotic Trialists' Collaboration published their meta-analysis of 287 randomized, placebo-controlled, antiplatelet trials in over 212,000 high risk patients, focused particularly on aspirin in cardiovascular disease.¹ This led to the demonstration of an overall potent benefit for the composite of vascular death, myocardial infarction and stroke. There was an apparent gradient of benefit with respect to individual outcomes: 34% reduction for myocardial infarction, 25% for stroke and 15% risk reduction for death. Of note, the maximum benefit was noted with doses of aspirin between 75-160 mg, and although the confidence intervals for the point estimate of benefit (32 vs 26% risk reduction) overlapped with the dose of 325 mg of aspirin, there was a noteworthy signal of low-dose aspirin being at least as good as standard-dose aspirin. Beyond the findings supportive of low-dose aspirin, the recommendations from the Trialists' were that diabetics should be considered for primary prevention with aspirin, and that there was utility in prophylaxis of systemic thromboembolism in patients with atrial fibrillation.

Second, the Clopidogrel for Unstable Angina Reduction of Endpoints (CURE) trial enrolled over 12,000 patients who received either aspirin and placebo or aspirin and clopidogrel on a double-dummy, double-blind basis.² The trial showed the benefit for the combination of aspirin and clopidogrel in the management of patients with acute ischemic heart disease. But for the first time in a very large prospective trial, which tracked bleeding complications, there was an impressive relationship of dose of aspirin (which ranged from 75-325 mg) and bleeding complications. There was a major two-fold increase of life-threatening, serious, or any bleeding complications for aspirin 325 mg as compared with aspirin <100 mg. The intermediate-dose (approximately 150-160 mg) trended more like low-dose aspirin, with a modest excess of bleeding complications. This dose-response relationship of aspirin and bleeding complications in the range of 75-325 mg had not been previously documented. Taken together with the efficacy results in CURE and the large meta-analysis, there is strong support to use the dose of 81-162 mg in the United States (doses of 75 mg or 150 mg are not available in this country) for primary or secondary prevention of atherothrombotic complications.

Third, recent data from Mangano et al in the setting of bypass surgery are quite remarkable.^3,4 In a large observational database of over 5,000 patients who were tracked for aspirin dosing in the first 48 hours after heart bypass surgery, there was a potent 60% reduction of fatalities, stroke, myocardial infarction, and virtually every important end-organ complication (eg, need for dialysis, encephalopathy) in the patients who received aspirin d