Vascular risks may vary among nonsteroidal anti-inflammatory drugs

High doses of diclofenac and possibly ibuprofen have comparable vascular risks to coxibs, whereas high-dose naproxen was associated with less vascular risk than other nonsteroidal anti-inflammatory drugs (NSAIDs), a meta-analysis found.

Researchers reviewed results from 280 trials of NSAIDs versus placebo, totaling 124,513 patients and 68,342 person-years, as well as results from 474 trials comparing one NSAID to another, totaling 229,296 participants and 165,456 person-years.

Results were published online by The Lancet on May 30.

Compared to placebo, major vascular events increased by about a third with a coxib (rate ratio [RR], 1.37, 95% CI, 1.14 to 1.66; P=0.0009) or diclofenac (RR, 1.41, 95% CI, 1.12 to 1.78; P=0.0036), mainly due to an increase in major coronary events (coxibs: RR, 1.76; 95% CI, 1.31 to 2.37; P=0.0001 and diclofenac: RR, 1.70; 95% CI, 1.19 to 2.41; P=0.0032). Ibuprofen also significantly increased major coronary events (RR, 2.22; 95% CI, 1.10 to 4.48; P=0.0253) but did not have a significant effect on major vascular events (RR, 1.44; 95% CI, 0.89 to 2.33).

Compared with those on placebo, the 1,000 patients allocated to a coxib or diclofenac for a year had three more major vascular events, one of which was fatal. Naproxen did not significantly increase major vascular events (RR, 0.93, 95% CI, 0.69 to 1.27). Vascular death increased significantly with coxibs (RR, 1.58; 99% CI, 1.00 to 2.49; P=0.0103) and diclofenac (RR, 1.65; 95% CI, 0.95 to 2.85; P=0.0187) and increased nonsignificantly with ibuprofen (RR, 1.90; 95% CI, 0.56 to 6.41; P=0.17) but did not increase with naproxen (RR, 1.08; 95% CI, 0.48 to 2.47; P=0.80).

All NSAID regimens increased upper gastrointestinal complications (coxibs: RR, 1.81; 95% CI, 1.17 to 2.81; P=0.0070; diclofenac: RR, 1.89, 95% CI, 1.16 to 3.09; P=0.0106; ibuprofen: RR, 3.97, 95% CI, 2.22 to 7.10; P<0.0001; and naproxen: RR, 4.22; 95% CI, 2.71 to 6.56; P<0.0001).

The researchers concluded, “Our meta-analysis, which is unaffected by selection and other biases inherent in observational studies, showed clearly that the vascular risks of diclofenac, and possibly ibuprofen, are similar to coxibs, but that naproxen is not associated with an increased risk of major vascular events. However, it also showed that the excess risk of both vascular and gastrointestinal events can be predicted once the baseline risks of such hazards are known, which could help clinical decision-making.”

An accompanying editorial noted that for 1,000 patients at moderate risk of heart disease, there would be about three major vascular events, including one death, due to a year of high-dose NSAIDs except for naproxen. For 1,000 patients at moderate risk of gastrointestinal complications, a year of high-dose NSAIDs would result in four to 16 gastrointestinal complications.