Pain Management Express Report

Publication date: 2003-06-13

Analgesic Treatment Options for Patients Taking Low-dose Aspirin for Cardioprotection

This report was reviewed for medical and scientific accuracy by Paula S. Krauser, MD, MA, Clinical Associate Professor, Department of Family Medicine, University of Medicine & Dentistry of New Jersey (UMDNJ)-Robert Wood Johnson Medical School, New Brunswick, New Jersey

Expert Commentary and Analysis by A. Mark Fendrick, MD, Division of General Internal Medicine, Department of Internal Medicine, School of Medicine; Department of Health Management and Policy, School of Public Health; University of Michigan, Ann Arbor, Michigan

Introduction

The results of a recently published study suggest that the concomitant administration of ibuprofen with aspirin may antagonize the cardioprotective effects of aspirin in patients with established cardiovascular disease.¹ Moreover, compared to patients using single-agent aspirin, patients taking aspirin plus ibuprofen had an increased risk of all-cause mortality and cardiovascular mortality. These findings support previously published data from Catella-Lawson et al that demonstrated that the concomitant use of ibuprofen, but not acetaminophen, diclofenac, or rofecoxib, antagonized the irreversible platelet inhibition induced by aspirin.²

Aspirin is widely utilized to reduce the risk of recurrent myocardial infarction and stroke in high-risk patients.^3,4 High-risk patients would include, but are not limited to, those with occlusive arterial disease, stable angina, intermittent claudication, and diabetes. However, because of comorbid diseases such as osteoarthritis, many high-risk patients with cardiovascular risk factors or established cardiovascular disease require additional pharmacologic therapies to address chronic pain and/or inflammation.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are available over-the-counter for a variety of uses and are widely prescribed for symptomatic relief for patients with arthritis.⁵ In fact, more than 30 million people worldwide take NSAIDs on a daily basis.⁶ As the population of the United States ages, it will become increasingly likely that many patients will be taking aspirin for its cardioprotective benefit and concomitant NSAIDs for their analgesic and/or anti-inflammatory properties.

In light of these recently published studies, clinicians must caution high-risk patients taking prophylactic aspirin for cardioprotection not to take ibuprofen. Fortunately, a multitude of alternative options to ibuprofen are available. Such options would include other NSAIDs and the cyclooxygenase (COX)-2 specific inhibitors. However, NSAIDs have been well documented for causing life-threatening toxicities in the form of gastric ulcers, gastrointestinal bleeding, and their complications (eg, perforation, pyloric obstruction).^7-11 The COX-2 specific inhibitors were developed as theoretically offering a lower risk of gastrointestinal complications than NSAIDs because these agents spare the action of COX-1, the enzyme responsible for producing gastroprotective prostaglandins. However, recent revelations concerning trial design have called into question the validity of the claim of lower risk of gastrointestinal complications with COX-2 specific inhibitors.^12,13 Moreover, there is much controversy surrounding the use of COX-2 specific inhibitors and their possible association with adverse cardiovascular events.¹⁴ In addition to their ability to diminish the antihypertensive effect of angiotensin-converting enzyme (ACE) inhibitors, COX-2 specific inhibitors are capable of inducing elevations in blood pressure.^15,16 Emerging evidence suggests than even small incremental increases in blood pressure (1 to 5 mm Hg) may result in significant additional ischemic heart disease and stroke events annually.¹⁷ For high-risk cardiovascular patients taking prophylactic aspirin for cardioprotection, the administration of NSAIDs and/or COX-2 specific inhibitors may exacerbate existing comorbidities.

Conver