Among the NSAIDs used for relieving the pain of inflammatory arthritis, naproxen may have the best benefit to risk ratio on cardiovascular disease (CVD), according to the most comprehensive analysis of the benefits and risks of NSAIDs, including cyclo-oxygenase 2 inhibitors, or coxibs.
“The vascular risks of high-dose diclofenac and ibuprofen are comparable to coxibs, while high-dose naproxen is associated with less vascular risk than other NSAIDs,” said one study author, Charles Hennekens, MD, DrPH, Senior Academic Advisor to the Dean in the Charles E. Schmidt College of Medicine at Florida Atlantic University. “Although NSAIDs increase vascular and gastrointestinal risks, their magnitude can be predicted, which may help guide clinical decision making.”
Under the direction of the Clinical Trial Service and Epidemiology Studies Unit at the University of Oxford, Dr Hennekens and colleagues from around the world conducted a worldwide meta-analysis. They used individual participant data from 280 trials of NSAIDs vs placebo and 474 trials of an NSAID vs another NSAID, which involved more than 350,000 participants and a total of more than 230,000 person-years. The study addressed the risks and benefits of drugs used for relief of inflammatory arthritis, including CVD and other relevant outcomes, such as GI effects.
The main outcomes were major vascular events (nonfatal myocardial infarction, nonfatal stroke, and vascular death); major coronary events (nonfatal myocardial infarction and coronary death); stroke; mortality; heart failure; and upper GI complications (perforation, obstruction, and bleeding).
Major vascular events were increased by about one-third by a coxib or diclofenac, chiefly because of an increase in major coronary events. Ibuprofen also significantly increased major coronary events but not major vascular events. Of 1000 patients allocated to a coxib or diclofenac for a year, 3 more had major vascular events, 1 of which was fatal, compared with placebo. Naproxen did not significantly increase major vascular events.
Vascular death was increased significantly by coxibs and diclofenac and was increased nonsignificantly by ibuprofen but was not increased by naproxen. The proportional effects on major vascular events were independent of baseline characteristics, including vascular risk.
Heart failure risk was roughly doubled by all NSAIDs. All NSAID regimens increased upper GI complications.
In conclusion, the authors wrote, “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.”
The authors emphasized that the risks are mainly relevant to persons who experience chronic pain, such as patients with arthritis who need to take high doses of NSAIDs, such as 150 mg of diclofenac or 2400 mg of ibuprofen daily, for long periods.
“In contrast to naproxen, other traditional NSAIDs and coxibs confer similar moderately increased risks of CVD,” said Dr Hennekens. “At present, individual clinical judgments about coxibs and nonselective NSAIDs should not be limited to risks of CVD. They should also include concerns about non-CVD risks, such as gastrointestinal bleeding, and other benefits, including improved quality of life resulting from decreases in impairment from musculoskeletal pain syndromes.”
The authors reported their results in the May 30 issue of The Lancet.