Ibuprofen Safety Questioned For High-Risk Cardio Patients – Study

Medical practitioners should use caution in prescribing ibuprofen to low-dose aspirin users who are considered high-risk for cardiac events, according to a study published in the June Annals of the Rheumatic Diseases.

Ibuprofen intake (800 mg three times daily) among a group of high-risk cardiovascular patients was associated with a 2.14 percent incidence of composite cardio outcomes and a 1.61 percent incidence of congestive heart failure, according to the study conducted by Dr. Michael E. Farkouh, a professor in the Mount Sinai School of Medicine cardiology division, et al.

Those results were compared to outcomes for similar patients taking COX-2 inhibitor lumiracoxib (400 mg once daily), which was associated with a 0.25 percent incidence of both composite cardio and congestive heart failure events.

"This finding has significant health implications," the researchers say. They note the findings are "consistent with previous evidence that ibuprofen can interfere with aspirin acetylation of the COX-1 binding site on platelets, thereby blocking aspirin-mediated inhibition of platelet aggregation."

In the 52-week, double-blind study, researchers set out to compare the risk of cardiac incidence among older osteoarthritis patients taking non-selective non-steroidal anti-inflammatory drugs ibuprofen or naproxen versus COX-2 inhibitor lumiracoxib.

Researchers evaluated two parallel sub-studies from the Therapeutic Arthritis Research and Gastrointestinal Event Trial published in 2004.

They identified 3,042 patients considered at high cardiovascular risk and 15,283 at low risk. Of high risk patients taking low-dose aspirin, 373 took ibuprofen, and were compared to 394 taking lumiracoxib, while 505 taking naproxen were compared to 541 taking lumiracoxib.

While ibuprofen was associated with a higher risk of cardiac events than lumiracoxib, the researchers found naproxen (500 mg twice daily) and lumiracoxib posed the same risk of cardiac event. Those results show the "relative cardiovascular safety" of naproxen versus lumiracoxib, Farkouh et al. say.

Intake of Naproxen - the active ingredient in Bayer's Aleve - was associated with a 1.58 percent incidence of composite cardio events and a 0.99 percent incidence of congestive heart failure, while lumiracoxib was associated with 1.48 percent and 1.11 percent incidences, respectively.

Among high-risk cardiac patients not taking low-dose aspirin, there was no difference between ibuprofen and lumiracoxib use, although naproxen was found to have a lower cardiovascular risk than lumiracoxib.

"This finding is consistent with the ability of naproxen to inhibit platelet aggregation in a similar way to aspirin," Farkouh et al. note. "However, unlike aspirin, persistent blood levels of naproxen are needed to maintain inhibition of platelet aggregation."

The researchers add "based on these findings, in high-risk patients not receiving aspirin, high-dose naproxen appears to have the lowest cardiovascular risk among the three agents studied."

In patients considered at low cardiovascular risk, there were no significant differences identified between the NSAIDs and the COX-2 inhibitor.

Farkouh et al. maintain the study is the first to evaluate "hard" cardiovascular outcomes related to aspirin use, NSAIDs and COX-2 inhibitors among high-risk cardio patients. However, they note as a "post hoc subgroup analysis, this study is subject to inherent limitations, and therefore should be interpreted as a hypothesis-generating study."

They conclude "a long-term, placebo controlled, randomized trial in the high cardiovascular risk population is required to evaluate further the cardiovascular safety of both selective and non-selective NSAIDs and to balance these risks with the associated gastrointestinal effects of these agents."

In a study released in 2006 by the Agency for Healthcare Research and Quality, traditional non-selective NSAIDs, excluding naproxen, were found to carry similar cardiovascular risk to COX-2 inhibitors (¹ (Also see "Naproxen Fares Better Than Ibuprofen In Cardiovascular-Risk Data" - Pink Sheet, 2 Oct, 2006.), p. 9).

- Eileen Francis ([email protected])