Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials.
Level 1 - systematic review of randomized trials
Individual participant data meta-analysis of randomized controlled trials
PubMed 23726390 · doi:10.1016/S0140-6736(13)60900-9
What was done
Individual participant data meta-analyses evaluated randomized trials comparing NSAIDs (coxibs and traditional NSAIDs) with placebo (280 trials; 124,513 participants; 68,342 person-years) and one NSAID with another (474 trials; 229,296 participants; 165,456 person-years). Primary outcomes were major vascular events (non-fatal myocardial infarction, non-fatal stroke, or vascular death), major coronary events, stroke, mortality, heart failure, and upper gastrointestinal complications (perforation, obstruction, or bleed).
What was found
Major vascular events were increased by roughly one-third by coxibs (rate ratio [RR] 1.37, 95% CI 1.14–1.66; p=0.0009) and diclofenac (RR 1.41, 95% CI 1.12–1.78; p=0.0036), adding 3 major vascular events (1 fatal) per 1000 patients annually compared to placebo. Ibuprofen (RR 1.44, 95% CI 0.89–2.33) and naproxen (RR 0.93, 95% CI 0.69–1.27) did not significantly increase major vascular events. Major coronary events increased with coxibs (RR 1.76, 95% CI 1.31–2.37; p=0.0001), diclofenac (RR 1.70, 95% CI 1.19–2.41; p=0.0032), and ibuprofen (RR 2.22, 95% CI 1.10–4.48; p=0.0253). Vascular death rose significantly with coxibs (RR 1.58, 99% CI 1.00–2.49; p=0.0103) and diclofenac (RR 1.65, 95% CI 0.95–2.85; p=0.0187), but not naproxen (RR 1.08, 95% CI 0.48–2.47). Heart failure risk roughly doubled across all NSAIDs. Upper gastrointestinal complications increased with coxibs (RR 1.81, 95% CI 1.17–2.81), diclofenac (RR 1.89, 95% CI 1.16–3.09), ibuprofen (RR 3.97, 95% CI 2.22–7.10), and naproxen (RR 4.22, 95% CI 2.71–6.56).
Why it matters
High-dose diclofenac has vascular risks similar to coxibs, whereas naproxen demonstrates lower vascular risk, though all NSAID classes double heart failure risk and elevate gastrointestinal complications.
Limits
The abstract does not specify drug doses beyond noting high-dose regimens in the conclusion, limiting conclusions regarding low-dose, intermittent, or over-the-counter use. Concomitant use of gastroprotective therapies or baseline participant comorbidities are not reported in the abstract.
Cited by
- supports Nonsteroidal anti-inflammatory drugs (NSAIDs) do not reduce cardiovascular disease risk.