Nonsteroid Anti-Inflammatory Drugs Hold Cardiovascular Risks

Researchers at the University of Bern (Switzerland) conducted a network meta-analysis that included 31 large-scale randomized controlled trials comparing any NSAID with other NSAIDs or placebo. A total of 116,429 patients taking naproxen, ibuprofen, diclofenac, celecoxib, etoricoxib, lumiracoxib, rofecoxib, or placebo were included, and the primary outcome was myocardial infarction (MI). Secondary outcomes included stroke, death from cardiovascular disease, and death from any cause. Two investigators independently extracted data; in all, more than 115,000 patient years of follow-up were included.

The researchers found an increase in MI, stroke, and cardiovascular death in patients taking all of these NSAIDs. Not surprisingly, rofecoxib, marketed by Merck (Darmstadt, Germany) as Vioxx, was associated with the highest risk for MI, with a rate ratio of 2.12; the drug was voluntarily withdrawn in 2004 due to concerns over cardiotoxicity. Lumiracoxib had the next highest rate of MI. Ibuprofen was associated with the highest risk for stroke, with a rate ratio of 3.36, followed by diclofenac at 2.86. Etoricoxib, on the other hand, was linked to the highest rate of cardiovascular death, at 4.07, followed by diclofenac at 3.98; of all the NSAIDs, naproxen seemed least harmful. The study was published online on January 11, 2011, in BMJ.

"I think we should reserve our final judgment on naproxen until after we've completed the overall safety study,” warned senior author Peter Jüni, MD, who is currently studying the gastrointestinal safety of the drug and weighing the benefits and risks from that perspective.
"With naproxen, we tend to need a proton pump inhibitor to protect the stomach; this is far from ideal.”

NSAIDs are medications with analgesic and antipyretic effects and which have, in higher doses, anti-inflammatory effects. The term nonsteroidal is used to distinguish these drugs from steroids, which, among a broad range of other effects, have a similar eicosanoid-depressing, anti-inflammatory action. As analgesics, NSAIDs are unusual in that they are non-narcotic. The most prominent members of this group of drugs are aspirin, ibuprofen, and naproxen, all of which are available over the counter (OTC) in many areas.

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