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STATE-OF-THE-ART PAPER

Coxibs and Heart Disease

What We Have Learned and What Else We Need to Know

Ignatius Gerardo E. Zarraga, MD^_* and Ernst R. Schwarz, MD, PhD, FACC^_*,,_*

^_* Division of Cardiology, Department of Internal Medicine, The University of Texas Medical Branch, Galveston, Texas
Division of Cardiology, Department of Internal Medicine, Cedars-Sinai Medical Center and University of California Los Angeles, Los Angeles, California

Manuscript received June 27, 2006; accepted August 8, 2006.

^_* Reprint requests and correspondence: Dr. Ernst R. Schwarz, Division of Cardiology, Cedars Sinai Medical Center, 8700 Beverly Boulevard, Suite 6215, Los Angeles, California 90048 (Email: Ernst.Schwarz{at}cshs.org).

Since their approval in 1998, the popularity of selective cyclooxygenase-2 (COX2) inhibitors has swung from a domination of drug sales to serious disputes about their cardiovascular safety. Despite the numerous studies on COX2 inhibitors that have emerged, drawing conclusions about their cardiovascular safety has been complicated by conflicting results, underpowered clinical trials, and the lack of a placebo group and use of post hoc analyses in many trials. Nonetheless, certain conclusions can be made with reasonable accuracy. This review addresses the controversy in 3 segments. It begins with a discussion of the several mechanisms proposed to explain how selective COX2 inhibition impacts the cardiovascular system. This is followed by a recount of the several clinical studies that delved into the cardiovascular outcomes associated with COX2 inhibitors. Finally, answers to key questions are provided to assist the clinician in devising a systematic approach to the risk-benefit analysis of COX2 inhibitors in actual practice.

Abbreviations and Acronyms   CABG = coronary artery bypass grafting   CAD = coronary artery disease   CHF = congestive heart failure   COX = cyclooxygenase   FDA = Food and Drug Administration   HR = hazard ratio   MI = myocardial infarction   NSAID = non-steroidal anti-inflammatory drug   OA = osteoarthritis   PG = prostaglandin   PPI = proton pump inhibitor   RA = rheumatoid arthritis   TX = thromboxane

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