EHJ: Coxibs may be off the hook for CV risk, but not AF

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Despite prior claims that cyclooxygenase-2 inhibitors (coxibs) increased cardiovascular risk in patients, results of a study published Nov. 21 in European Heart Journal found no association of coxibs with increased risk of MI or ischemic stroke; however, the drug class was found to be linked to atrial fibrillation.

“Nonsteroidal anti-inflammatory drugs (NSAIDs) are inhibitors of cyclooxygenase (COX), the enzyme responsible for the initial step in the metabolism of arachidonic acid into prostaglandins and thromboxane,” Magnus Back, of the Karolinska University Hospital in Stockholm, and colleagues wrote.

“Whereas the cardio protective effects of aspirin are well established, the cardiovascular safety of other NSAIDs, and especially for the selective inhibitors of the COX-2 isoform (coxibs, cyclooxygenase-2 inhibitors), has remained controversial. Several randomized controlled trials (RCTs) of long-term use of selective coxibs indicated an increased risk of myocardial infarction, stroke and heart failure compared with either other NSAIDs or placebo.”

In September 2004, after warnings of increased CV risk with selective coxibs use, the FDA withdrew rofecoxib (Vioxx, Merck) from the market. Rofecoxib came under fire after researchers found a 100 percent increased CV risk linked to the drug, and APPROVe trial results showed that the drug produced a 79 percent increased CV risk, according to a study published 2010 in the Archives of Internal Medicine.

To better define the potential association of coxib use and future risk of CV events, Back and colleagues performed an analysis of 6,991,645 subjects from population-based data from the Prescribed Drug, Patient, Cause of Death, Income, Educational and Emigration Registers from July 1, 2005, to Dec. 31, 2008.

Of the patients who received COX-2 inhibitors, 41.8 percent received celecoxib and 58.2 percent received etoricoxib. Coxib exposure was lower in subjects with a prior cardiovascular event (prior MI: 1.69 percent; prior ischemic stroke: 1.68 percent, prior HF: 1.32 percent and prior AF: 1.65 percent).

When data were adjusted on the basis of age, sex and socioeconomic status, the authors found coxib to be associated with an increased risk of MI, ischemic stroke, HF and atrial fibrillation. However, after a fully adjusted analysis, coxib use increased the risk for only AF.

“Although the partially adjusted analysis in the present study indicated a significantly increased risk for incident myocardial infarction and ischemic stroke, these observations did not persist after adjustment for rheumatoid and cardiovascular co-morbidities,” Back and colleagues wrote. During the study, the authors found an increased CV risk associated with rheumatoid arthritis, a patient group commonly prescribed coxibs.

“In summary, the present recent nationwide cohort study, initiated after the cardiovascular safety of coxibs was taken into consideration, indicates no significant association of coxibs with increased risk of myocardial infarction or ischemic stroke,” the authors wrote.

The researchers summed that many have taken precautions when prescribing coxibs and NSAIDs to patients, after warnings of the potential for the increased risk for CV side effects.

“In contrast, a possible increased risk of atrial fibrillation may have been overlooked, and may necessitate consideration and precautions,” the researchers summed.