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NSAIDs and COX-2 agents, but not naproxen, pose vascular risk to adults

Clinical Question:
How common are adverse vascular and gastrointestinal events among nonsteroidal anti-inflammatory drugs?

Bottom Line:
Diclofenac, ibuprofen, and COX-2 inhibitors (coxibs) cause more vascular complications than placebo. (LOE = 1a)

Coxib and traditional NSAID Trialists’ (CNT) Collaboration. Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials. Lancet 2013, early online publication May 30, 2013. http://dx.doi.org/10.1016/S0140-6736(13)60900-9 [PMID:23726390]

Study Design:
Meta-analysis (randomized controlled trials)


Outpatient (any)

These authors (who have an impressive list of ties to industry) searched multiple databases to find published and unpublished randomized trials of at least 4 weeks' duration that compared a nonsteroidal anti-inflammatory drug (NSAID) against placebo, open controls, or another NSAID. In addition to analyzing the studies using standard meta-analytic approaches, the researchers also tried to obtain patient-level data. They evaluated the rate of major vascular events (defined as nonfatal myocardial infarction, nonfatal stroke, or death from a vascular cause), major coronary events (nonfatal myocardial infarction or death from coronary disease), stroke, hospitalization, and upper gastrointestinal complications (bleeding, perforation, or obstruction). Two authors independently assessed studies for inclusion and extracted study characteristics and data. The authors don't describe how discrepancies were resolved or whether they formally assessed study quality. Ultimately, they included 280 placebo-controlled trials (with more than 124,000 patients) and 470 trials comparing NSAIDs to NSAIDs (nearly 230,000 patients). Most of the trials lasted less than 1 year. The included trials provided approximately 90% of the available data to the researchers. Compared with placebo, patients taking a coxib expereinced more major vascular events (1.2% per year) than patients taking placebo (0.8% per year; number needed to treat to harm [NNTH] = 250 per year), more admissions for heart failure (0.7% vs 0.3% per year; NNTH = 250), deaths from all causes (1.7% vs 1.4% per year; NNTH = 417), and upper gastrointestinal (GI) complications (0.4% vs 0.2% per year; NNTH = 527). In studies comparing a coxib with diclofenac, the patients taking coxibs had lower annual rates of major vascular events (0.8% vs 1.1%; number needed to treat [NNT] = 358); heart failure admissions (0.9% vs 1.7%; NNT = 117); and upper GI complications (0.7% vs 1.2%; NNT = 193). Compared with ibuprofen, patients taking coxibs were less likely to be admitted for heart failure (0.4% vs 1.6% per year; NNT = 82) and upper GI complications (0.2% vs 0.6% per year; NNT = 257). Finally, in studies comparing coxibs and naproxen, patients taking coxibs had lower annual rates of heart failure admissions (0.8% vs 1.8%; NNT = 98) and upper GI complications (0.3% vs 0.5%; NNT = 477).


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