Blog | Friday, May 31, 2013

QD: News Every Day--Restrict high-dose, long-term NSAIDs to those who understand the risks

The vascular risks of high-dose diclofenac, and possibly ibuprofen, are comparable to coxibs, whereas high-dose naproxen is associated with less vascular risk than other NSAIDs, a study concluded.

Compared with placebo, of 1,000 patients allocated to a coxib or diclofenac for a year, three more had major vascular events, one of which was fatal, researchers reported in a meta-analysis of 280 randomized trials of NSAIDs versus placebo that looked at nearly 125,000 people and 474 trials of one NSAID versus another that looked at more than 229,000 people. Results appeared online May 30 at The Lancet.

Major vascular events increased by about a third in patients taking a coxib (rate ratio [RR] 1.37; 95% confidence interval [CI], 1.14 to 1.66; P=0.0009) or diclofenac (RR, 1.41; 95% CI, 1.12 to 1.78; P=0.0036), chiefly due to an increase in major coronary events (coxibs: RR, 1.76; 95% CI, 1.31 to 2.37; P=0.0001; 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 not major vascular events (RR, 1.44; 95% CI, 0.89 to 2.33). Naproxen did not significantly increase major vascular events (RR, 0.93; 95% CI, 0.69 to 1.27).

Vascular death was increased significantly by 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), nonsignificantly by ibuprofen (RR, 1.90; 95% CI, 0.56 to 6.41; P=0.17), but not by 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 less than 0.0001; naproxen: RR, 4.22; 95% CI, 2.71 to 6.56; P less than 0.0001).

Authors wrote that the study "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 editorial noted that someone prone to vascular or gastrointestinal outcomes wiuld occur a 4% to 19% risk of requiring treatment over 10 years of taking NSAIDs.

The editorial stated, "These risks translate to a high drug-related burden of morbidity and mortality in populations where NSAID use is common. Individuals taking NSAIDs, especially at high doses, incur substantial risk when drug use persists for extended periods," and "long-term use of high dose NSAIDs should be reserved for those who receive considerable symptomatic benefit from the treatment and understand the risks."