Cardiovascular Events after Prescription of Nsaids-updated Systematic Review of Pharmaco-epidemiological Studies

Patricia McGettigan, David A Henry

Research output: Contribution to journalMeeting AbstractResearchpeer-review

6 Citations (Scopus)


Background: Meta ‐ analyses of randomised trials have generated estimates of cardiovascular risk with NSAIDs in high doses.

Objectives: We wished to provide updated estimates of the risk of cardiovascular complications with typical community use of NSAIDs.

Methods: Systematic review and meta ‐ analysis of community ‐ based controlled observational studies published between 2000 and 2010. We used random effects models to pool adjusted RR values for major cardiovascular events with recent use of individual NSAIDs, in different doses, and in populations at low and high background risks of cardiovascular events. We compared individual drugs in a number of pair ‐ wise (within study) analyses.

Results: Twenty eight reports of case ‐ control studies included 184,946 cardiovascular events, and 23 cohort studies described outcomes in over 2.3 million exposed individuals. Of the extensively studied drugs the highest RR values were seen with rofecoxib 1.5, (95% CI 1.3, 1.6) and diclofenac 1.4 (1.3, 1.5) and the lowest were seen with celecoxib, 1.2 (1.1, 1.3) and naproxen, 1.1 (1.0, 1.2). Based on sparse data, etoricoxib, 2.1 (1.5, 2.9) and etodolac, 1.6 (1.3, 1.9) appear to have elevated risks. Pair ‐ wise comparisons found etoricoxib to have a significantly higher RR than ibuprofen (RRR 1.68; 99%CI 1.1, 2.5) and naproxen (1.75; 1.2, 2.6) but not significantly higher than rofecoxib and diclofenac. Indomethacin had a higher RR than naproxen (RRR 1.2; 1.1, 1.4). Naproxen had a significantly lower RR than ibuprofen (RRR 0.92; 0.87, 0.99), but not celecoxib. Both ibuprofen and celecoxib had elevated RR in higher doses, a pattern not seen with naproxen.

Conclusions: The data for etoricoxib and etodolac are sparse but raise safety concerns. Diclofenac is concerning as it is available without prescription in several countries and has increased cardiovascular risk at low doses. Naproxen has an advantage over ibuprofen and celecoxib; both have an elevated risk at higher doses. Indomethacin is an old drug with multiple toxicities; the cardiovascular risk profile highlighted here suggests that clinicians should now abandon it.
Original languageEnglish
Article number748
Pages (from-to)S324-S325
Number of pages2
JournalPharmacoepidemiology and Drug Safety
Issue numberS1
Publication statusPublished - 2011
Externally publishedYes


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