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

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DOI:

https://doi.org/10.59471/ijhsc2022118

Keywords:

Cyclooxygenase-2 inhibitors, NSAIDS, Risk Factors, Thrombosis, Acute Myocardial Infarction

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.

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References

SOGAC. Los antiinflamatorios no esteroideos en Reumatología [Internet]. 2016. https://sogacot.org/los-antiinflamatorios-no-esteroideos-en-reumatologia/.

Bäck M, Yin L, Ingelsson E. Cyclooxygenase-2 inhibitors, and cardiovascular risk in a nationwide cohort study after the withdrawal of rofecoxib. Eur Heart J. 2012;33(15):1928-33. https://doi.org/10.1093/eurheartj/ehr421.

Orellana I. Inhibidores de Cox2 en gastroenterología. Medwave. 2003;3(01). http://doi.org/10.5867/medwave.2003.02.2334.

Domper Arnal MJ, Hijos-Mallada G, Lanas A. Gastrointestinal and cardiovascular adverse events associated with NSAIDs. Expert Opin Drug Saf. 2022;21(3):373-384. https://doi.org/10.1080/14740338.2021.1965988.

Abraham NS, El-Serag HB, Hartman C, Richardson P, Deswal A. Cyclooxygenase-2 selectivity of non-steroidal anti-inflammatory drugs and the risk of myocardial infarction and cerebrovascular accident. Aliment Pharmacol Ther. 2007;25(8):913-24. https://doi.org/10.1111/j.1365-2036.2007.03292.x.

Batlouni M. Anti-inflamatórios não esteroides: Efeitos cardiovasculares, cérebro-vasculares e renais. Arq Bras Cardiol. abril de 2010; 94:556-63. Sharma JN, Jawad NM. Adverse effects of COX-2 inhibitors. ScientificWorldJournal. 2005;5:629-45. https://doi.org/10.1100/tsw.2005.82.

E. Rahme, H. Nedjar, Risks and benefits of COX-2 inhibitors vs non-selective NSAIDs: does their cardiovascular risk exceed their gastrointestinal benefit? A retrospective cohort study. Rheumatology. 2007;46(3):435–438, https://doi.org/10.1093/rheumatology/kel428.

Lee T, Lu N, Felson DT, Choi HK, Dalal DS, Zhang Y, et al. Use of non-steroidal anti-inflammatory drugs correlates with the risk of venous thromboembolism in knee osteoarthritis patients: a UK population-based case-control study. Rheumatology (Oxford). 2016;55(6):1099-105. https://doi.org/10.1093/rheumatology/kew036.

Angiolillo DJ, Weisman SM. Clinical Pharmacology and Cardiovascular Safety of Naproxen. Am J Cardiovasc Drugs. 2017;17(2):97–107. https://doi.org/10.1007/s40256-016-0200-5.

Capone ML, Tacconelli S, Di Francesco L, Sacchetti A, Sciulli MG, Patrignani P. Pharmacodynamic of cyclooxygenase inhibitors in humans. Prostaglandins Other Lipid Mediat. 2007;82(1–4):851. https://doi.org/10.1016/j.prostaglandins.2006.05.019.

Sánchez Serrano JL, Tenias Burillo JM, Arias Arias Á, Muñoz Carreras MI, Valenzuela Gámez JC. Riesgo cardiovascular asociado al consumo de antiinflamatorios no esteroideos: estudio de cohortes retrospectivo en un área de salud, 2008-2012. Revista Española de Salud Pública. 2015;89(6):607-13. https://doi.org/10.4321/s1135-57272015000600008.

McGettigan P, Henry D (2011) Cardiovascular Risk with Non-Steroidal Anti-Inflammatory Drugs: Systematic Review of Population-Based Controlled Observational Studies. PLoS Med 8(9):e1001098. https://doi.org/10.1371/journal.pmed.1001098.

Bäck M, Yin L, Ingelsson E. Cyclooxygenase-2 inhibitors, and cardiovascular risk in a nationwide cohort study after the withdrawal of rofecoxib. Eur Heart J. 2012;33(15):1928-33. https://doi.org/10.1093/eurheartj/ehr421.

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Published

2022-12-01

How to Cite

1.
Costa Leite Lucio Silva R, Estrin MA. Cardiovascular risk associated with the use of selective COX-2 inhibitors: a systematic review. Interamerican Journal of Health Sciences [Internet]. 2022 Dec. 1 [cited 2024 Mar. 29];(2):118. Available from: https://ijhsc.com/journal/article/view/118

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