Abstract

Background: Non steroidal anti-inflammatory drugs(NSAIDs) utilization has been associated with worsened outcomes among patients with established cardiovascular disease.We analyzed the cause-specific cardiovascular risk associated with use of NSAIDs in a nationwide cohort of patients with prior myocardial infarction (MI). Methods: By individual-level linkage of nationwide registries of hospitalizations and drug dispenses from pharmacies in Denmark, patients aged >30 years admitted with first-time MI during 1997-2009 and their subsequent NSAID use were identified. The risk of cardiovascular death, a composite of coronary death or nonfatal MI, and fatal or nonfatal stroke with NSAID use was analyzed by adjusted Cox proportional hazard models. Results: Of 97,698 patients included (mean age 69 years (SD 13.0), 63.0% men),44.0% received NSAIDs during follow-up. Relative to no NSAID use, overall NSAID was associated with an increased risk of cardiovascular death (hazard ratio [HR] 1.52 95% confidence interval [CI] 1.34-1.73). In particular, use of the nonselective NSAID diclofenac and the selective cyclooxygenase-2 (COX-2) inhibitor rofecoxib was associated with increased risk of cardiovascular death (HR 2.05 95% confidence interval CI 1.88-2.23) and HR 1.74(CI.1.53-1.98), respectively) with a dose dependent increase in risk. Use of ibuprofen was associated with increased risk of fatal/nonfatal stroke (HR 1.27(CI. 1.14-1.41)).Naproxen was associated with the lowest risk of all outcomes, although higher than no NSAID use. Conclusion: The cause specific cardiovascular risks associated with the use of individual NSAIDs found to differ and in particular rofecoxib and diclofenac were associated with increased cardiovascular morbidity and mortality. These results further support caution in use of NSAIDs in patients with prior MI.

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