Patients with atrial fibrillation (AF) receiving antithrombotic treatment are at increased risk for bleeding if they also take a nonsteroidal anti-inflammatory drug (NSAID), even for a short period, a new nationwide Danish study has found.

The data suggest that a serious bleeding event occurs in up to 1 in 400 to 500 patients with AF exposed to an NSAID for 2 weeks and that the risk is elevated with both selective cyclooxygenase (COX)-2 inhibitors and nonselective NSAIDs.

The findings are important because NSAIDs are so widely available and commonly used, commented lead study author Morten Lamberts, MD, PhD, Department of Cardiology, Gentofte University Hospital, Hellerup, Denmark.

“Any safety issues are a major public health concern,” said Dr Lamberts. “Patients should know that it’s possible that even over-the-counter drugs might put them at increased bleeding and thromboembolic risk.”

The study is published in the November 18 issue of Annals of Internal Medicine.
The researchers used data from the Denmark’s National Patient Registry, which contains information on hospitalizations and on dosage, strength, and date of dispensed prescription drugs. The analysis included 150,900 patients, median age 75 years, who were hospitalized with a first-time diagnosis of AF between 1997 and 2011. During a median follow-up of 6.2 years, 35.6% of patients were prescribed an NSAID.
Study participants had a mean HAS-BLED (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/alcohol concomitantly) score of 1.5 and mean CHA2DS2VASc (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke, vascular disease, sex) score of 2.8. Approximately 70% were being treated with an antiplatelet or oral anticoagulant.

Investigators categorized rofecoxib and celecoxib as selective COX-2 inhibitors and ibuprofen, diclofenac, and naproxen as nonselective NSAIDs. Since 2001, ibuprofen has been the only NSAID available in Denmark without a prescription, but only in low doses and in limited quantities. Since that time, this agent has accounted for 15% to 20% of all NSAID sales.

The study showed that serious bleeding events, including intracranial and gastrointestinal bleeding, occurred in 11.4% of the patients and thromboembolic events in 13.0%. The absolute risk for serious bleeding with 14 days of continuous NSAID exposure was 3.5 events per 1000 patients vs 1.5 events per 1000 patients without NSAID exposure, with an absolute risk difference of 1.9 events per 1000 patients. In patients selected for oral anticoagulant therapy, the absolute risk difference was 2.5 events per 1000 patients.

“This suggests a serious bleeding event in 1 of 400 to 500 patients exposed to an NSAID for 14 days,” the authors write.