Cardiovascular risk associated with the use of selective COX-2 inhibitors: a systematic review

Abstract

Introduction: Selective inhibitors of the enzyme cyclooxygenase-2 were developed to reduce the gastrointestinal toxicity of conventional nonsteroidal anti-inflammatory drugs. However, this class of drugs decreases prostacyclin production and can disrupt endothelial homeostatic balance, leading to a prothrombotic state that offsets potential gastrointestinal benefits.Methods: A systematic review of all study publications linking cyclooxygenase-2 inhibitor nonsteroidal anti-inflammatory drugs and related cardiovascular events was performed.Results: The highest overall risks were seen with rofecoxib, 1.45 (95% CI 1.33 to 1.59), and diclofenac, 1.40 (1.27 to 1.55). The lowest risks recorded were with ibuprofen, 1.18 (1.11, 1.25), and naproxen, 1.09 (1.02, 1.16). The risk of VTE increased with diclofenac [OR 1.63 (95% CI: 1.53, 1.74)], ibuprofen [OR = 1.49 (95% CI: 1.38, 1.62)], meloxicam [OR = 1.29 (95% CI: 1.11, 1.50)] and coxibs [celecoxib, OR= 1.30 (95% CI: 1.11, 1.51); rofecoxib, OR= 1.44 (95% CI: 1.18, 1.76)]. Naproxen did not increase the risk of VTE [OR = 1.00 (95% CI: 0.89, 1.12)]. Furthermore, there is a significant association with atrial fibrillation for etoricoxib (HR 1.35; 95% CI 1.19–1.54). Conclusion: This review suggests that the risk of these adverse effects is greater in patients with an earlier history of cardiovascular disease or at considerable risk for developing it. Evidence shows that among the widely used NSAIDs, low-dose naproxen and ibuprofen are less likely to increase cardiovascular risk. Data for etoricoxib were sparse, but in pairwise comparisons this drug had a significantly higher relative risk than either naproxen or ibuprofen. Indomethacin is an older drug that is also toxic to the gastrointestinal system, and evidence of cardiovascular risk casts doubt on its continued clinical use.