Cyclooxygenase-2 inhibitors and cardiovascular risk in a nation-wide cohort study after the withdrawal of rofecoxib

• Published in: European heart journal Vol. 33; no. 15; pp. 1928 - 1933
• Main Authors: Back, M., Yin, L., Ingelsson, E.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.08.2012
• Subjects: Atherosclerosis (general aspects, experimental research); Atrial Fibrillation - chemically induced; Atrial Fibrillation - mortality; Biological and medical sciences; Blood and lymphatic vessels; Bones, joints and connective tissue. Antiinflammatory agents; Cardiac dysrhythmias; Cardiology. Vascular system; Cardiovascular Diseases - chemically induced; Cardiovascular Diseases - mortality; Celecoxib; Coronary heart disease; Cyclooxygenase 2 Inhibitors - adverse effects; Epidemiologic Methods; Female; Heart; Heart Failure - chemically induced; Heart Failure - mortality; Humans; Lactones - adverse effects; Male; Medical sciences; Middle Aged; Myocardial Infarction - chemically induced; Myocardial Infarction - mortality; Pharmacology. Drug treatments; Prognosis; Pyrazoles - adverse effects; Safety-Based Drug Withdrawals; Stroke - chemically induced; Stroke - mortality; Sulfonamides - adverse effects; Sulfones - adverse effects; Sweden - epidemiology; Sweden; Myocardial infarction; Rofecoxib; Arrhythmia; Eicosanoids; Cardiovascular disease; Cyclooxygenase 2 inhibitor; Myocardial disease; Vascular disease; Prostaglandins; Treatment withdrawal; Eicosanoid; Cohort study; Atherosclerosis; Cardiology; Cerebrovascular disease; Heart failure; Nervous system diseases; Poison withdrawal; Prostaglandin; Atrial fibrillation; Inflammation; Coronary heart disease; Excitability disorder; Cerebral disorder; Non steroidal antiinflammatory agent; Central nervous system disease; Risk factor; Circulatory system
• ISSN: 0195-668X; 1522-9645; 1522-9645
• DOI: 10.1093/eurheartj/ehr421

The use of selective cyclooxygenase (COX)-2 inhibitors (coxibs) has been associated with an increased cardiovascular risk. The aim of the present study was to evaluate the association of coxib use and future risk of cardiovascular events in a population-based cohort followed after the warnings concerning the cardiovascular safety of this class of drugs were issued. A nation-wide, population-based cohort of 7 million subjects, integrating data from the Prescribed Drug, Patient, Cause of Death, Income, Educational and Emigration Registers, was followed from 1 July 2005 to 31 December 2008. Analyses were performed for different cardiovascular outcomes in the whole population after exclusion of individuals with prior cardiovascular diagnosis (incident primary cardiovascular events; sample size, n = 6 991 645). Cox proportional hazard ratios (HRs) revealed no significant association of coxib use with risk for myocardial infarction, ischaemic stroke, or heart failure. In contrast to these findings, coxib use was associated with an increased risk for a first episode of atrial fibrillation [HR 1.16; 95% confidence interval (CI) 1.05-1.29]. A post hoc analysis for different coxibs revealed a significant association with incident atrial fibrillation for etoricoxib (HR 1.35; 95% CI 1.19-1.54) but not for celecoxib (HR 0.94; 95% CI 0.79-1.11). Whereas safety measures appear to have limited serious cardiovascular consequences of COX-2 inhibitors, the risk of developing atrial fibrillation may have been overlooked and may necessitate consideration and precautions.