Relation of Nonsteroidal Anti-Inflammatory Drugs to Serious Bleeding and Thromboembolism Risk in Patients With Atrial Fibrillation Receiving Antithrombotic Therapy: A Nationwide Cohort Study | Journal Scan

Study Questions:

What is the risk for serious bleeding and thromboembolism in patients with atrial fibrillation (AF) using both nonsteroidal anti-inflammatory drugs (NSAIDs) and antithrombotics?


Using Danish national registries, patients hospitalized for AF between 1997 and 2011 were identified. The risk for serious bleeding and thromboembolism within a 14-day window associated with concurrent NSAID and antithrombotic medications was assessed using Cox models.


Of 150,900 patients with AF, 53,732 (35.6%) were prescribed an NSAID at any point during a mean follow-up of 6.2 years (interquartile range, 2.1-14.0 years) and 105,279 (69.8%) were treated with an antiplatelet or anticoagulant medication. There were 17,187 (11.4%) and 19,561 (13.0%) occurrences of serious bleeding and thromboembolism, respectively. After 3 months of antithrombotic exposure, the absolute risk for serious bleeding was 3.5 events per 1,000 patients (with NSAID exposure) versus 1.5 events per 1,000 patients (without NSAID exposure), an absolute difference of 1.9 events per 1,000 patients. In patients treated with anticoagulants, the difference in serious bleeding between those with and without NSAID exposure was 2.5 events per 1,000 patients. There was a similar, but smaller, absolute risk increase for serious bleeding with NSAID exposure. The hazard ratio with ongoing NSAID use was 3.54 (95% confidence interval [CI], 3.29-3.82) for gastrointestinal bleeding and 1.22 (95% CI, 1.03-1.44) for intracranial bleeding. Use of NSAIDs above the recommended dosage limit was associated with a substantially increased hazard ratio for bleeding.


The authors concluded that use of NSAIDs was associated with an independent risk for serious bleeding and thromboembolism in AF patients.


This analysis describes the risk of major bleeding and thromboembolism associated with NSAID use in AF patients on antithrombotic medications. Of particular concern is the concurrent use of NSAIDs and oral anticoagulants, even with short courses of NSAID use. Understanding the risks of bleeding and thrombosis with their use is important to share with patients. Of note, use of NSAIDs above their recommended doses was associated with a further increase in the risk of major bleeding, highlighting the need to comply with dosing guidelines if NSAIDs are being used.

Clinical Topics: Anticoagulation Management, Arrhythmias and Clinical EP, Anticoagulation Management and Atrial Fibrillation, Atrial Fibrillation/Supraventricular Arrhythmias

Keywords: Anticoagulants, Anti-Inflammatory Agents, Non-Steroidal, Atrial Fibrillation, Fibrinolytic Agents, Gastrointestinal Hemorrhage, Hemorrhage, Thromboembolism

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