Reference number: OPUSeJ 201303052316CRN
Links: to published article http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.1001098
Title: Cardiovascular Risk with Non-Steroidal Anti-Inflammatory Drugs: Systematic Review of Population-Based Controlled Observational Studies
Authors: Patricia McGettigan & David Henry
Background: Randomised trials have highlighted the cardiovascular risks of non-steroidal anti-inflammatory drugs (NSAIDs) in high doses and sometimes atypical settings. Here, we provide estimates of the comparative risks with individual NSAIDs at typical doses in community settings.
Methods and Findings: We performed a systematic review of community-based controlled observational studies. We conducted comprehensive literature searches, extracted adjusted relative risk (RR) estimates, and pooled the estimates for major cardiovascular events associated with use of individual NSAIDs, in different doses, and in populations with low and high background risks of cardiovascular events. We also compared individual drugs in pair-wise (within study) analyses, generating ratios of RRs (RRRs). Thirty case-control studies included 184,946 cardiovascular events, and 21 cohort studies described outcomes in >2.7 million exposed individuals. Of the extensively studied drugs (ten or more studies), the highest overall risks were seen with rofecoxib, 1.45 (95% CI 1.33, 1.59), and diclofenac, 1.40 (1.27, 1.55), and the lowest with ibuprofen, 1.18 (1.11, 1.25), and naproxen, 1.09 (1.02, 1.16). In a sub-set of studies, risk was elevated with low doses of rofecoxib, 1.37 (1.20, 1.57), celecoxib, 1.26 (1.09, 1.47), and diclofenac, 1.22 (1.12, 1.33), and rose in each case with higher doses. Ibuprofen risk was seen only with higher doses. Naproxen was risk-neutral at all doses. Of the less studied drugs etoricoxib, 2.05 (1.45, 2.88), etodolac, 1.55 (1.28, 1.87), and indomethacin, 1.30 (1.19, 1.41), had the highest risks. In pair-wise comparisons, etoricoxib had a higher RR than ibuprofen, RRR = 1.68 (99% CI 1.14, 2.49), and naproxen, RRR = 1.75 (1.16, 2.64); etodolac was not significantly different from naproxen and ibuprofen. Naproxen had a significantly lower risk than ibuprofen, RRR = 0.92 (0.87, 0.99). RR estimates were constant with different background risks for cardiovascular disease and rose early in the course of treatment.
Conclusions: This review suggests that among widely used NSAIDs, naproxen and low-dose ibuprofen are least likely to increase cardiovascular risk. Diclofenac in doses available without prescription elevates risk. The data for etoricoxib were sparse, but in pair-wise comparisons this drug had a significantly higher RR than naproxen or ibuprofen. Indomethacin is an older, rather toxic drug, and the evidence on cardiovascular risk casts doubt on its continued clinical use.
Author bio: N/A
Sponsor editor: Brian L. Strom, University of Pennsylvania School of Medicine, USA.
Patricia McGettigan: Hull York Medical School, Hull, United Kingdom
David Henry: Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada, Department of Medicine, University of Toronto, Toronto, Ontario, Canada, Discipline of Clinical Pharmacology, School of Medicine and Public Health, University of Newcastle, Newcastle, Australia.
Our thanks are due to Paula Clark and Bill McGuire for assistance with the searches and to the authors who supplied additional data from their studies. The authors have declared that no competing interests exist. Corresponding Author: firstname.lastname@example.org
Subject: Medicine/ NSAIDs
Bibliography: see Forum
Citation: McGettigan, Patricia and David Henry, 2011, “Cardiovascular Risk with Non-Steroidal Anti-Inflammatory Drugs: Systematic Review of Population-Based Controlled Observational Studies”, PLoS Med 8(9): e1001098. doi:10.1371/journal.pmed.1001098 http://www.plosmedicine.org/article/info%3Adoi%2F10.1371%2Fjournal.pmed.1001098