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REVIEW ARTICLE

Nonsteroidal Anti-Inflammatory drugs and cardiovascular risk

Patricia A. Howard, PharmD, FCCP, BCPS (AQ CV)^*,* and Patrice Delafontaine, MD, FACC, FESC, FAHA, FACP

^* Department of Pharmacy Practice, University of Kansas Medical Center, Kansas City, Kansas, USA
Division of Cardiovascular Diseases, University of Kansas Medical Center, Kansas City, Kansas, USA

Manuscript received March 6, 2003; revised manuscript received June 3, 2003, accepted September 10, 2003.

^* Reprint requests and correspondence: Dr. Patricia A. Howard, Department of Pharmacy Practice, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, Kansas 66160-7231, USA.
phoward{at}kumc.edu

Nonsteroidal anti-inflammatory drugs (NSAID) inhibit cyclooxygenase (COX) enzymes, which exist in at least two isoforms, COX-1 and COX-2. Aspirin and older agents in this class are nonselective inhibitors of both COX-1 and COX-2. Newer agents termed "coxibs" are selective inhibitors of COX-2. Among the NSAID, only aspirin has been proven to significantly reduce cardiovascular risk, primarily through inhibition of COX-1-mediated platelet aggregation. It has been suggested that other nonselective agents, especially naproxen, may provide some lesser degree of cardioprotection, but conclusive evidence is lacking. Conversely, there are concerns that the COX-2 inhibitors may increase cardiovascular risk. However, mechanisms for this potentially adverse cardiovascular effect are unknown, and it is becoming increasingly clear that our understanding of the role of COX-2 in cardiovascular function is incomplete. Some studies have demonstrated a potentially beneficial effect of COX-2 on cardiovascular function that could be negated by COX-2 inhibition, while other studies have reported improved endothelial function with COX-2 inhibitors. Additionally, the impact of combined therapy with aspirin and other COX inhibitors is not yet clear. This article will review the studies that have examined these issues.

Abbreviations and Acronyms   CHD = coronary heart disease   CLASS = Celecoxib Long-term Arthritis Safety study   COX = cyclooxygenase   MI = myocardial infarction   NANSAID = nonaspirin nonsteroidal anti-inflammatory drugs   NSAID = nonsteroidal anti-inflammatory drugs   VIGOR = Vioxx Gastrointestinal Outcomes Research study

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