The use of nonsteroidal anti-inflammatory drugs (NSAIDs) is very frequent and many of these medications are sold over-the-counter, but they can expose patients with atrial fibrillation using warfarin or dabigatran to potentially dangerous bleeding. Such a combination is a “perfect storm” of sorts, since atrial fibrillation is the most frequent type of arrhythmia and its incidence increases with age, the use of NSAIDs also increases with age mainly due to osteoarticular pain, access to these drugs is free in most countries, and the risk of bleeding also increases with age.

This post hoc analysis in the RE-LY study assessed 2279 patients who reported concomitant use of any NSAID at least once during the study.

The parent study included 18,113 patients with atrial fibrillation and randomized them to dabigatran 110 or 150 mg every 12 hours vs. warfarin.

All analyzed groups presented a higher risk of bleeding with NSAIDs, including major bleeding (Hazard ratio [HR]: 1.68; 95% confidence interval [CI]: 1.40-2.02), gastrointestinal major bleeding (HR: 1.81; 95% CI: 1.35-2.43), and stroke or systemic embolism (HR: 1.50; 95% CI: 1.12-2.01).

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Patients who used NSAIDs at least once were also more frequently hospitalized (HR: 1.64; 95% CI: 1.51-1.77); however, their use did not affect the rates of intracranial bleeding, acute myocardial infarction, and all-cause mortality.

The risk of stroke or systemic embolism is 2% per year among patients who use NSAIDs and anticoagulant agents vs. 1.4% among patients who only receive anticoagulant therapy (p = 0.007). The rate of ischemic stroke experiences the highest rise with the use of NSAIDs.

The increase in the risk of bleeding is related with platelet inhibition and the reduction of the protection provided by the gastric mucosa, which implies that twice the effort is needed for more appropriate pain management (pharmacological or not) in these subjects. However, this is not limited to this population and should be applied to all patients, given the risk entailed by NSAIDs and the current epidemic of opioid abuse.

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In this study, only 16.5% of patients using NSAIDs were treated with proton-pump inhibitors. In any case, blocking acid production does not prevent distal duodenal bleeding and may even increase it through the alteration of gastrointestinal microbiota.

Original title: Concomitant Oral Anticoagulant and Nonsteroidal Anti-Inflammatory Drug Therapy in Patients with Atrial Fibrillation.

Reference: Kent AP et al. J Am Coll Cardiol 2018;72:255-267.

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