Cardiovascular safety of NSAIDs.

Evidence • Meta-analysis of 754 RCTs (about 350 000 patients)1: -Mixed population, primarily patients with arthritis at low to moderate CV risk (ie, CV event rate about 1% per year). -Use of COX-2 inhibitors compared with placebo increased —all-cause mortality, rate ratio (RR) = 1.22 (95% CI 1.04 to 1.44); and —serious CV events, RR = 1.37 (95% CI 1.14 to 1.66). -Diclofenac (150 mg daily): similar risks to COX-2 inhibitors for mortality (RR = 1.02 [95% CI 0.84 to 1.24]) and CV events (RR = 0.97 [95% CI 0.84 to 1.12]). —Indirectly, diclofenac significantly increases CV events (RR = 1.41 [95% CI 1.12 to 1.78; P = .0036]) but not mortality (RR = 1.20 [95% CI 0.94 to 1.54]) compared with placebo. -Naproxen (1000 mg daily) is associated with fewer CV events and lower mortality than COX-2 inhibitors and might be similar to placebo. -Relative risk similar between patients with and without existing CV disease. • Meta-analysis of observational trials2: -All COX-2 inhibitors and NSAIDs except naproxen and low-dose ibuprofen (≤ 1200 mg daily) increase CV risk. -Risk increases with increasing NSAID dose. • Results are consistent with previous meta-analysis.3