Ibuprofen Cancels Heart Benefit of Aspirin

In the high-risk patients the aspirin-ibuprofen regimen was associated with 2.14% primary cardiovascular event rate versus a 0.25% rate among patients taking lumiracoxib, an investigational selective Cox-2 inhibitor, and aspirin (P=0.038).

That finding, published online ahead of print in the Annals of Rheumatic Diseases, emerged from a post-hoc analysis of data from the 18,325-patient TARGET (Therapeutic Arthritis Research and Gastrointestinal Event Trial).

The ibuprofen finding, the authors wrote, supports earlier studies that suggested ibuprofen blocks aspirin-mediated inhibition of platelet aggregation, negating aspirin's ability to reduce the risk of thrombotic events. Moreover, high-risk patients taking ibuprofen were also more likely to develop congestive heart failure compared with patients taking lumiracoxib (1.28% versus 0.34%, P=0.031).

By contrast, in a parallel trial that compared naproxen to lumiracoxib, high risk patients using naproxen but no low-dose aspirin had no events versus an event rate of 1.57% among patients using the Cox-2 inhibitor and without aspirin prophylaxis (P=0.027). Among high-risk patients taking aspirin and naproxen, the event rate was 1.58% versus 1.48% for those taking lumiracoxib plus aspirin (P=0.899).

"These findings, although limited by the post hoc design of the study, and the small number of events in the subgroups of interest, suggest that caution is warranted in prescribing ibuprofen to high risk patients," the authors wrote.

TARGET was comprised of parallel substudies that compared lumiracoxib to either naproxen or ibuprofen. The post hoc analysis was performed by baseline cardiovascular risk, study treatment, and low-dose aspirin use.

The ibuprofen substudy, however, included "a significantly higher number of patients with diabetes and dyslipidemia but a lower number of patients with a history of cerebrovascular or cardiovascular disease than the naproxen substudy (P<0.0001 for all comparisons)," the authors wrote.

In addition to the finding that ibuprofen use was associated with increased cardiovascular events, the study also found that naproxen at a daily dose of 500 mg demonstrated "relative cardiovascular safety" compared with 400 mg of lumiracoxib.
The authors noted that it is still not clear whether naproxen has cardioprotective effects, but among high-risk patients in this analysis, naproxen had the lowest cardiovascular risk of three drugs studied.

Because TARGET was a 12-month trial, the findings may not reflect long-term cardiovascular risks that have been reported for both non-selective NSAIDs such as naproxen and Cox-2 inhibitors such as lumiracoxib.

Practice Pearls:  Explain to interested patients that this report suggests the need for caution when using ibuprofen in patients at high risk for cardiovascular events who are also taking low-dose aspirin

Source: Diabetes In Control: Farkouh M. "Cardiovascular outcomes in high-risk patients with osteoarthritis treated with Ibuprofen, Naproxen or Lumiracoxib" Ann Rheum Dise 2007; 000:1-7.