Abstract 3805: The Use of COX-2 Inhibitors and the Risk of Myocardial Infarction in the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA) Trial
Background Cyclo-oxygenase 2 (COX-2) inhibitors have been associated with an increased risk of myocardial infarction (MI). We examined this association in the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA) trial.
Methods The CHARISMA trial randomized both patients with established cardiovascular disease and patients at high risk for atherothrombosis to receive aspirin and clopidogrel vs. aspirin and placebo. We divided the patients into those who had used a COX-2 inhibitor medication for any length of time either before or during the study and into those who had not been exposed to COX-2 inhibitors. Patients who used COX-2 inhibitors only after they suffered an MI were included as not having been exposed. We determined the incidence of MI in the two groups over a mean follow-up of 28 months.
Results There were a total of 386 MIs among the 15,603 patients in the CHARISMA study. We excluded 4 MIs, because it was not clear whether or not COX-2 inhibitor use preceded the MI. The risk of MI was similar among the patients who had used COX-2 inhibitors and among the patients who had not been exposed to COX-2 inhibitors: 2.56% (50/1,952) vs. 2.43% (332/13,647), respectively, hazard ratio = 1.020 (95% confidence interval: 0.757 - 1.373), p-value = 0.898. Dual antiplatelet therapy with aspirin and clopidogrel did not alter the risk estimate compared to therapy with aspirin only.
Conclusion This is the largest randomized trial to assess COX-2 inhibition with prospective adjudication of MI events. Our findings do not demonstrate an increased risk of MI with the use of COX-2 inhibitors.