NSAIDs Plus Anticoagulants a Bad Combination

LONDON, England—Patients with A-fib who are taking a nonsteroidal anti-inflammatory drug (NSAID) in addition to dabigatran or warfarin are more likely to bleed and be hospitalized, according data from the RE-LY trial presented September 1, 2015, at the European Society of Cardiology Congress. Yet the advantage of dabigatran over warfarin is evident irrespective of whether patients are on NSAIDs.

RE-LY, published in 2009, randomized 18,113 patients to receive dabigatran at 110 or 150 mg twice daily or warfarin. Dabigatran demonstrated similar or better effectiveness than warfarin in preventing stroke or systemic embolism, with equal or lower risk of major bleeding.

For the current analysis, Michael D. Ezekowitz, MD, of Jefferson Medical College (Philadelphia, PA), and colleagues identified 2,279 patients (12.6%) who used an NSAID at least once during the course of RE-LY.

Patients receiving NSAIDs were more likely than those who never took drugs in that class to be female and have valvular heart disease but less likely to present with congestive heart failure. Other baseline characteristics were similar in the 2 groups.

Bleeding, Hospitalization Increased

NSAID use was accompanied by increases in the rates of hospitalization, major bleeding, GI major bleeding, life-threatening bleeding, and any bleeding. However, other endpoints including death, MI, and intracranial bleeding did not differ by NSAID use (table 1).

 
There were no significant interactions between treatment arm and NSAID use for endpoints including stroke or systemic embolism, major bleeding, hemorrhagic stroke, life-threatening bleeding, or intracranial bleeding. “Patients in the RE-LY trial who received NSAIDs derived similar relative benefits from dabigatran compared with warfarin,” Dr. Ezekowitz concluded, noting that bleeding rates were lowest with the 110-mg dabigatran dose.

Based on these findings, “the combination of NSAIDs with any oral anticoagulant requires a careful benefit-risk assessment,” he advised.

Session moderator Sigrun Halvorsen, MD, PhD, of Oslo University Hospital Ullevål (Oslo, Norway), asked what is known about the duration of NSAID use in RE-LY.

Dr. Ezekowitz replied that such an analysis has not been done yet. “It turns out to be a rather complicated analysis, because patients come on and off the drug,” he said. “There are periods of very long use, periods of very short use—that analysis needs to be done.”

Agreeing that such calculations would be complicated, Dr. Halvorsen stressed that, “nevertheless, it is [important] to answer this question in more detail.”

Source: 
Ezekowtiz M. Clinical outcomes of atrial fibrillation patients receiving NSAIDs in the RE-LY trial. Presented at: European Society of Cardiology Congress; September 1, 2015; London, England.

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• Meta-analysis: Good Bleeding Profile with Dabigatran vs. Warfarin for A-fib, VTE