Using ibuprofen for OA increases heart attack risk in patients on aspirin therapy

Congestive heart failure developed more often among ibuprofen-treated patients compared to patients receiving selective COX-2 inhibitors.

Osteoarthritis patients who are at high risk for cardiovascular events are nine times more likely to experience myocardial infarction when taking aspirin and ibuprofen combined, according to a large scale study.

Michael E. Farkouh, MD, an associate professor of medicine and cardiology at Mount Sinai School of Medicine, New York, and colleagues compared rates of cardiovascular mortality among patients who either were or were not on low-dose aspirin therapy and who were also treated with either ibuprofen, Aleve [naproxen, Bayer HealthCare] or the COX-2 inhibitor Prexige [lumiracoxib, Novartis].

The study, called the Therapeutic Arthritis Research and Gastrointestinal Event Trial — High Risk (TARGET-HR), included 18,523 osteoarthritis (OA) patients over 50 years of age. The results are published online ahead of print on the Web site for the journal Annals of the Rheumatic Diseases.

Studies have previously shown an increased risk of cardiovascular events from treating with selective COX-2 inhibitors and nonselective NSAIDs. However, little research has focused on patients at high cardiovascular risk who take aspirin in combination with these drugs for OA, according to a press release from Mount Sinai Medical Center announcing the study findings.

"Ibuprofen has a significantly higher rate of major cardiovascular events, mostly heart attacks, when compared to a COX-2 inhibitor," Farkouh, lead investigator for the study, said in the release.

"The findings underscore the importance of not only considering the class of NSAIDs used in high-risk cardiac patients with osteoarthritis but also making physicians aware of the interaction of NSAIDs with aspirin, diminishing any beneficial effects," he said.

Investigators found that, among patients with OA at high cardiovascular risk and not taking low-dose aspirin, patients who received lumiracoxib had a higher heart attack rate than patients receiving naproxen. However, lumiracoxib-treated patients had a similar heart attack rate to patients receiving ibuprofen, according to the release.

Among these non-aspirin-treated patients, those receiving naproxen had a 0% rate of primary events compared to a rate of 1.57% for those receiving lumiracoxib (P = .027). In comparison, those receiving ibuprofen had a 0.92% rate of primary events vs. a 0.8% rate for those on lumiracoxib (P = .92), according to the study.

For patients at high cardiovascular risk who were using low-dose aspirin, investigators found a higher incidence of cardiovascular events associated with ibuprofen. Patients receiving ibuprofen had a 2.14% rate of primary events vs. 0.25% for those receiving lumiracoxib (P = .038), but rates were similar between patients receiving either naproxen (1.58%) or lumiracoxib (1.48%; P = .899), according to the study.

Overall, congestive heart failure developed more often among ibuprofen-treated patients (1.28%) than among lumiracoxib-treated patients (0.14%; P = .031), but no difference was noted between naproxen- and lumiracoxib-treated patients, the study authors noted.

The findings show ibuprofen interferes with aspirin's effects in high cardiovascular risk patients, the release said.

"This is the first randomized trial evidence to show risk of interaction between ibuprofen and aspirin to be real," Farkouh noted in the release.

"Doctors should not give high-risk cardiovascular patients ibuprofen for pain while they are taking aspirin for their heart. Cardiologists, rheumatologists and gastroenterologists need to work together to fully evaluate the evidence at hand to make proper recommendations to primary care physicians," he said.

For more information:
Farkouh ME, Greenberg JD, Jeger RV, et al. Cardiovascular outcomes in high-risk patients with osteoarthritis treated with ibuprofen, naproxen, or lumiracoxib. Ann Rheum Dis. April 5, 2007 [Epub ahead of print].