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ANALGESIA

Cardiovascular Thromboembolic Adverse Effects Associated with Cyclooxygenase-2 Selective Inhibitors and Nonselective Antiinflammatory Drugs

Girish P. Joshi, MBBS, MD, FFARCSI^*, Ralph Gertler, MD, and Ruth Fricker, MD

From the *Department of Anesthesiology and Pain Management, University of Texas Southwestern Medical Center, Dallas, Texas; Institute of Anesthesiology and Intensive Care, German Heart Centre of the State of Bavaria and the Technical University Munich; and Pfizer GmbH, Karlsruhe, Germany.

Address correspondence and reprint requests to Girish P. Joshi, MBBS, MD, FFARCSI, Department of Anesthesiology and Pain Management, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390-9068. Address e-mail to girish.joshi{at}utsouthwestern.edu.

Abstract

BACKGROUND: Concerns of increased cardiovascular (CV) thromboembolic adverse effects from nonsteroidal antiinflammatory drugs (NSAIDs, both nonselective [NS]-NSAIDs and cyclooxygenase [COX]-2 selective inhibitors) have prevented their use despite numerous benefits.

METHODS: In this descriptive review, we critically examine the randomized, active- and placebo-controlled studies, observational trials, and meta-analyses evaluating the CV adverse effects associated with long-term and short-term use of COX-2 selective inhibitors and NS-NSAIDs. The potential mechanisms for these CV effects are also presented.

RESULTS: Although the studies evaluating the CV risks have limitations, there appears to be an increased CV risk with both COX-2 selective inhibitors and NS-NSAIDs, particularly in high-risk patients. Therefore, the United States Food and Drug Administration has given a similar "boxed" warning highlighting the potential for increased risk of CV events associated with their use. Nevertheless, there are differences in the CV risks between COX-2 selective inhibitors (e.g., higher CV risk with rofecoxib than celecoxib) as well as differences in the CV risks between individual NS-NSAIDs (e.g., higher CV risks with diclofenac than naproxen).

CONCLUSIONS: Until long-term, prospective, randomized, adequately powered, clinical studies in relevant patient populations have been completed, the CV risks associated with the use of NSAIDs, especially in high-risk patients, will likely continue to be controversial. Nevertheless, the benefits of their short-term (e.g., perioperative) use in patients without CV risks probably outweigh their potential CV adverse effects. Finally, careful risk/benefit assessment should be undertaken and both COX-2 selective inhibitors and NS-NSAIDs should be used with caution in patients with CV risk factors.