• The authors of this observational cohort study of over 150,000 Danish patients with atrial fibrillation (AF) hospitalized from 1997 to 2011 examined the risk for serious bleeding and thromboembolism associated with NSAID and antithrombotic therapy. At 3 months, the absolute risk difference for serious bleeding in patients taking NSAIDs vs those not taking NSAIDs was 1.9 events per 1000 patients. The absolute risk difference in patients who received oral anticoagulant therapy was 2.5 events per 1000 patients.

• Use of NSAIDs in patients with AF is associated with increased risk for serious bleeding and thromboembolism.

Written by Peter Lin MD, CCFP
Be Careful With NSAIDs and Anticoagulants

We all know that NSAIDs use with anticoagulation increases the risk for bleeding. However, this has not been studied systematically in large numbers of people. This study looked at over 150,000 Danish patients with atrial fibrillation (AF); 53,000 had exposure to NSAIDs.

This study showed that NSAIDs use increased bleeding risk by at least twofold. Interestingly, the hazard ratio at 3 months was higher than at 2 years. This means that even short-term use of NSAIDs carries a high risk as well. The investigators also looked at individual NSAIDs, and it turns out that they all are not associated with the same degree of risk. The highest risk was with associated with rofecoxib, followed by diclofenac and then naproxen.

This study reminds us to make sure patients are not on NSAIDs if they are on anticoagulants. The study could not track over-the-counter (OTC) NSAIDs, so we must also warn our patients of those products. Most patients do not know what the OTC NSAIDs are, so I tend to give my patients a list the brand names and tell them not to use them. Hopefully, this way unnecessary bleeds can be avoided while patients are on anticoagulation therapy.

Abstract

BACKGROUND
Nonsteroidal anti-inflammatory drugs (NSAIDs) are assumed to increase bleeding risk, but their actual relation to serious bleeding in patients with atrial fibrillation (AF) who are receiving antithrombotic medication is unknown.

OBJECTIVE
To investigate the risk for serious bleeding and thromboembolism associated with ongoing NSAID and antithrombotic therapy.

DESIGN
Observational cohort study.

SETTING
Nationwide registries.

PATIENTS
Danish patients with AF hospitalized between 1997 and 2011.

MEASUREMENTS
Absolute risk for serious bleeding and thromboembolism with ongoing NSAID and antithrombotic therapy, assessed by using Cox models.

RESULTS
Of 150 900 patients with AF (median age, 75 years [interquartile range, 65 to 83 years]; 47% female), 53 732 (35.6%) were prescribed an NSAID during a median follow-up of 6.2 years (interquartile range, 2.1 to 14.0 years). There were 17 187 (11.4%) and 19 561 (13.0%) occurrences of serious bleeding and thromboembolism, respectively. At 3 months, the absolute risk for serious bleeding within 14 days of NSAID exposure was 3.5 events per 1000 patients compared with 1.5 events per 1000 patients without NSAID exposure. The risk difference was 1.9 events per 1000 patients. In patients selected for oral anticoagulant therapy, the absolute risk difference was 2.5 events per 1000 patients. Use of NSAIDs was associated with increased absolute risks for serious bleeding and thromboembolism across all antithrombotic regimens and NSAID types. An NSAID dosage above the recommended minimum was associated with a substantially increased hazard ratio for bleeding.

LIMITATION
Observational design and unmeasured confounders.

CONCLUSION
Use of NSAIDs was associated with an independent risk for serious bleeding and thromboembolism in patients with AF. Short-term NSAID exposure was associated with increased bleeding risk. Physicians should exercise caution with NSAIDs in patients with AF.

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Journal Abstract