NSAIDs with Anticoagulants Are “Double Trouble” for AF Patients

Using oral anticoagulants and nonsteroidal anti-inflammatory drugs (NSAIDs) together increases the risk for major bleeding and stroke in patients with atrial fibrillation (AF), according to a new analysis.

“The use of NSAIDs was associated with increased risk of major bleeding, stroke/systemic embolism, and hospitalization,” writes senior author Michael Ezekowitz, MD, PhD, professor of medicine at Thomas Jefferson University in Philadelphia in the article published in the Journal of the American College of Cardiology.

Ezekowitz and his colleagues conducted a post-hoc analysis of more than 18,000 patients in Randomized Evaluation of Long Term Anticoagulant Therapy (RE-LY) trial, a trial that was funded by Boehringer Ingelheim GmbH. The post hoc analysis, however, did not have a funding source. 

The study compared dabigatran etexilate (Pradaxa) 150 mg and 110 mg twice daily with warfarin (Coumadin) in patients with atrial fibrillation.

The researchers found that major bleeding and gastrointestinal bleeding was significantly elevated with NSAID use. The rate of stroke or systemic embolism (SE) with NSAID use was also significantly elevated, and patients were more frequently hospitalized if they used an NSAID.

However, the post-hoc analysis found that myocardial infarction rates were similar to NSAID use compared with non-NSAID use.

In an accompanying editorial, Sam Schulman, MD, PhD, professor in the Division of Hematology and Thromboembolism at McMaster University in Hamilton, ON, and James Aisenberg, MD, clinical professor and gastroenterologist at the Icahn School of Medicine at Mount Sinai in New York, questioned whether concomitant use of anticoagulants and NSAIDs signal “double trouble.”.

NSAIDs have been associated with an increased risk of both cardiovascular events and bleeding in AF patients-a risk that is augmented by anticoagulation, Schulman and Aisenberg write.

NSAIDs use has increased primarily due to over-the-counter purchase by patients, Schulman and Aisenberg write. From 2009 through 2014, NSAID use was 2.1 times more common among individuals with cardiovascular disease than those without cardiovascular disease. In addition, between 1999 and 2004, 11.6% of adults regularly used nonaspirin NSAIDs.

Unfortunately, intensive research and drug development have not yet solved the NSAIDs- anticoagulants problems, they say. “Oral prostaglandin analogues decrease gastrointestinal bleeding, but cause treatment-limiting side effects,” Schulman and Aisenberg write. “In addition, some selective COX-2 inhibitors have been withdrawn from the market due to a higher risk of myocardial infarction (rofecoxib, Vioxx) than other COX-2 inhibitors (celecoxib, Celebrex).

However, celecoxib does not increase the risk of nonfatal stroke or cardiovascular death versus placebo, according to the authors. In comparison to nonselective NSAIDS, celecoxib is also associated with a smaller increase in risk for serious bleeding when combined with an oral anticoagulant.