NSAIDs associated with less vascular risk

Naproxen may be the safest anti-inflammatory — at least when it comes to cardiovascular risk — according to a new study. Researchers from the United Kingdom undertook a meta-analysis of 280 trials of non-steroidal anti-inflammatory drugs (NSAIDs) vs placebo and 474 trials of one NSAID vs another. Main outcomes were major vascular events, major coronary events, stroke, mortality, heart failure, and upper gastrointestinal (GI) complications including bleeding. All NSAIDs and COX-2 inhibitors (coxibs) increased major vascular events except for naproxen (rate ratio [RR], coxibs 1.37 [95% confidence interval (CI), 1.14-1.66; P = 0.0009] and diclofenac 1.41 [95% CI, 1.12-1.78; P = 0.0036] mostly due to an increase in major coronary events). Ibuprofen also significantly increased the risk of major coronary events (RR 2.22, 95% CI, 1.10-4.48; P = 0.0253), but not major vascular events. Naproxen did not significantly increase the risk of major vascular events. Coxibs and diclofenac also significantly increased risk of vascular death, and there was a nonsignificant increase with ibuprofen, while there was no increase with naproxen. Heart failure risk was roughly doubled by all NSAIDs. The risk of upper GI complications was lowest with coxibs and highest with naproxen (coxibs 1.81, 95% CI, 1.17-2.81; P = 0.0070; diclofenac 1.89, 95% CI, 1.16-3.09; P = 0.0106; ibuprofen 3.97, 95% CI, 2.22-7.10; P < 0.0001, and naproxen 4.22, 95% CI, 2.71-6.56; P < 0.0001). The authors conclude that the vascular risks of diclofenac and possibly ibuprofen are comparable to coxibs, whereas high-dose naproxen is associated with less vascular risk (but higher GI risk) than other NSAIDs (Lancet published online May 30, 2013). The authors speculate that high-dose naproxen has fewer cardiovascular effects because it is the strongest inhibitor of COX-1, resulting in near complete suppression of platelet thromboxane biosynthesis (thus blocking platelet aggregation) throughout the 12-hour dosing interval.