Pain Management Express Report

Publication date: 2003-09-12

Concurrent Use of Nonsteroidal Anti-inflammatory Drugs and Aspirin: Effect on Aspirin's Cardioprotection

This report was reviewed for medical and scientific accuracy by Ronald S. Freudenberger, MD, Director of Heart Failure and Transplant Cardiology, Associate Professor of Medicine, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick, New Jersey

Introduction

The cardioprotective effects of aspirin have been clearly demonstrated in numerous clinical trials.^1-3 However, the results of several clinical trials have raised speculation over whether the beneficial cardioprotective effects of aspirin are diminished when aspirin is used in combination with nonsteroidal anti-inflammatory drugs (NSAIDs). The most recent publication was a subgroup analysis of a 5-year randomized, double-blind, placebo-controlled trial originally designed to examine the effect of regular use, intermediate use, or no use of NSAIDs and their impact on the cardioprotective effects of aspirin.⁴ The study concluded that regular, but not intermittent use of NSAIDs, inhibited the cardioprotective benefits of aspirin.

The results of this study confirm the findings of MacDonald and Wei⁵ who also determined the inhibitory effects of NSAIDs on aspirin and concluded that patients with known cardiovascular disease treated with aspirin plus ibuprofen versus patients treated with aspirin alone had an increased risk of all-cause mortality and cardiovascular mortality. Similarly, Catella-Lawson et al⁶ found that the concomitant use of ibuprofen, but not rofecoxib, acetaminophen, or diclofenac antagonized the irreversible platelet inhibition induced by aspirin thus potentially reducing the cardioprotective effects of aspirin.

The results of these trials raise understandable concern over the use of NSAIDs in patients taking aspirin for cardioprotection. NSAIDs are readily available over-the-counter and are widely used both over-the-counter and by prescription on a regular basis for patients with arthritis.⁷ It is estimated that more than 30 million people worldwide take NSAIDs on a daily basis.⁸ As the population of the United States (U.S.) ages, it becomes increasing likely that more people will be utilizing aspirin for its cardioprotective effects, as well as NSAIDs for their analgesic and/or anti-inflammatory properties.

Acetaminophen can be used as a viable alternative to NSAIDs in patients using aspirin for cardioprotection. In addition to not modifying the antiplatelet action of aspirin,⁶ acetaminophen may be routinely used in patients with congestive heart failure, hypertension, anticoagulant therapy, and a history of gastrointestinal complications. Due to its lack of antiplatelet interference and superior gastrointestinal safety profile, acetaminophen should be given appropriate consideration in patients on cardioprotective aspirin therapy requiring analgesic treatment.

Inhibition of Cardioprotective Benefits of Aspirin by NSAIDs

A recently published clinical trial demonstrated that regular use of NSAIDs inhibited the cardioprotective benefits of aspirin.⁴ This subgroup analysis is from a 5-year randomized, double-blind, placebo-controlled trial in 22,071 apparently healthy U.S. male physicians (The Physicians Health Study⁹). Patients randomized to 325 mg of aspirin every other day or placebo were examined for their utilization of NSAIDs and were stratified into 3 groups: no use, intermittent use (1-59 days per year), and regular use (≥60 days per year). The objective of the study was to determine whether NSAIDs inhibit the clinical benefit of aspirin on first myocardial infarction. During a mean follow-up of 5-years, 378 myocardial infarctions were confirmed, 139 of which occurred in the aspirin group and 239 in the placebo group (relative risk 0.56, 95% Confidence Interval (CI), 0.45-0.70). When further assessed, intermediate use of NSAIDs was not