Increased risk of MI with COX-2 inhibitors among patients with history of MI


In a large, population-based, case-control study, rofecoxib and celecoxib were associated with an excess risk of acute myocardial infarction (MI) in patients with a history of MI.

Key Points

Current consensus recommendations from the American Gastroenterology Association suggest that cyclo-oxygenase-2 (COX-2) inhibitors should be avoided in patients at greater risk of cardiovascular events.

The authors stated that this was the first study to adequately assess the risk of cardiovascular side effects associated with COX-2-selective inhibitors in patients with a history of MI.

Upon multivariate logistic regression, current users of rofecoxib were at an increased risk for MI regardless of whether they had a history of MI (RR=1.23; 95% CI, 1.05–1.45 for patients without a history of MI; RR=1.59; 95% CI, 1.15–2.18 for patients with a history of MI; P=.14 for both). In patients with a history of MI, celecoxib increased the risk of MI (RR=1.40; 95% CI, 1.06–1.84; P=.04), but patients without a previous MI did not experience an increased risk with celecoxib (RR=1.03; 95% CI, 0.88–1.20; P=.04). The use of traditional NSAIDs (ie, ibuprofen) or naproxen was not associated with an increased risk of MI, regardless of patient history of MI (RR=1.00; 95% CI, 0.75–1.34, and RR=1.24; 95% CI, 0.83–1.84, respectively). Too few patients received meloxicam to provide an appropriate assessment of its potential for cardiotoxicity.

The authors stated that the mechanism behind the cardiovascular toxicity of COX-2 inhibitors is related to the resulting imbalance between the antiplatelet-aggregating activity of prostacyclin and the proplatelet-aggregating activity of thromboxane that occurs with the use of these specific agents. Rofecoxib causes a more severe imbalance than celecoxib, which, according to the authors, may explain the greater cardiovascular toxicity demonstrated with rofecoxib in this study.

The authors stated that a large, randomized trial could best determine the safety of celecoxib and NSAIDs in this population.


Brophy JM, Lévesque LE, Zhang B. The coronary risk of cyclo-oxygenase-2 inhibitors in patients with a previous myocardial infarction. Heart. 2007;93:189–194.

Wilcox CM, Allison J, Benzuly K, et al. Consensus development conference on the use of nonsteroidal anti-inflammatory agents, including cyclooxygenase-2 enzyme inhibitors and aspirin [erratum in: Clinical Gastroenterol Hepatol. 2006;4:1421]. Clinical Gastroenterol Hepatol. 2006;4:1082–1089.

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