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THERAPEUTIC CONTROVERSIES

Nonselective Nonsteroidal Antiinflammatory Drugs and Cardiovascular Risk: Are They Safe?

Assistant Clinical Professor of Medicine, Division of Clinical Pharmacology and Toxicology, University of Colorado Health Sciences Center; Rocky Mountain Poison and Drug Center; NewFields, Denver, CO

Aaron Brody, BSc

Faculty of Medicine, Hebrew University of Jerusalem, Hadassah Medical Center, Ein Karem, Jerusalem, Israel

Scott D Phillips, MD

Associate Clinical Professor of Medicine, Division of Clinical Pharmacology and Toxicology, University of Colorado Health Sciences Center; Rocky Mountain Poison and Drug Center; NewFields

Reprints: Dr. Waksman, 730 17th St., Suite 925, Denver, CO 80202, fax 303/294-9220, javier.waksman{at}uchsc.edu

OBJECTIVE: To assess possible cardiovascular risks associated with use of nonselective nonsteroidal antiinflammatory drugs (NSAIDs).

DATA SOURCES: MEDLINE and EMBASE were searched from January 1985 through April 2007 and relevant studies were retrieved.

STUDY SELECTION AND DATA EXTRACTION: Peer-reviewed, prospective, double-blind, case-control, and cohort-design studies published in the English language literature were considered eligible for review. Previous meta-analyses and systematic reviews were also analyzed. In total, 17 case-control studies; 9 cohort studies; 1 prospective, double-blind study; 3 meta-analyses; and 1 systematic review of observational studies were identified.

DATA SYNTHESIS: Three studies were prospective and the remainder consisted of observational, retrospective studies, with most reporting acute fatal or nonfatal myocardial infarction as the cardiovascular endpoint. Among the nonselective NSAIDs, diclofenac appears to pose the highest risk for cardiovascular toxicity; other agents trend toward a neutral effect with respect to cardiovascular risk. Although the data are suggestive, it remains unclear whether naproxen provides protective cardiovascular effects among patients on chronic therapy.

CONCLUSIONS: Currently available data are insufficient for defining evidence-based clinical guidelines for the use of NSAIDs, and the need for additional research, specifically randomized controlled trials, is evident. Diclofenac demonstrates a significant risk while naproxen appears to pose the lowest, albeit nonsignificant, risk for cardiovascular morbidity. Although the current clinical evidence may not warrant recommending naproxen as the preferred NSAID treatment, it may be prudent to avoid diclofenac for patients with cardiovascular risk factors requiring NSAID treatment.

Key Words: nonsteroidal antiinflammatory drugs, COX-2 inhibitors, myocardial infarction

Published Online, July 3, 2007. www.theannals.com, DOI 10.1345/aph.1H341