Patient-Oriented Evidence That Matters

Direct Oral Anticoagulants Preferred Over Warfarin for Nonvalvular Atrial Fibrillation in Patients Also Taking Low-Dose Aspirin


Am Fam Physician. 2018 Dec 1;98(11):683.

Clinical Question

What is the best approach to anticoagulation for patients with nonvalvular atrial fibrillation who also take low-dose aspirin?

Bottom Line

The balance of benefits and harms favors direct oral anticoagulants over warfarin (Coumadin) for patients with nonvalvular atrial fibrillation who require anticoagulation and are already taking low-dose aspirin. It is worth noting that for low-risk patients with nonvalvular atrial fibrillation, aspirin alone is an option. Because these patients were largely taking aspirin as a secondary prevention for cardiovascular disease, edoxaban (Savaysa) was least likely to increase the risk of myocardial infarction. (Level of Evidence = 1a)


Many patients with atrial fibrillation have a separate indication for aspirin. This meta-analysis performed a thorough search of several databases and identified four randomized trials with a total of 21,722 patients who had nonvalvular atrial fibrillation and were taking antiplatelet therapy (most commonly low-dose aspirin) for cardiovascular prevention. Each of the studies randomized patients to receive warfarin or a direct oral anticoagulant such as edoxaban, apixaban (Eliquis), rivaroxaban (Xarelto), or dabigatran (Pradaxa). The studies had between 1.8 and 2.8 years of follow-up. The mean age of included patients was between 70 and 72 years, approximately one-third were women, and between 10% and 55% had experienced a previous stroke. After performing a random effects meta-analysis, the authors found that patients randomized to receive direct oral anticoagulants were less likely to experience a stroke or systemic embolism (hazard ratio [HR] = 0.78; 95% confidence interval [CI], 0.67 to 0.91) or vascular death (HR = 0.85; CI, 0.76 to 0.93) than those randomized to receive warfarin. There was a trend toward a higher risk of myocardial infarction in the direct oral anticoagulant group, primarily driven by the one dabigatran trial (HR = 1.2; CI, 0.97 to 1.4), but a trend toward fewer major hemorrhages with direct oral anticoagulants (HR = 0.83; CI, 0.69 to 1.01). Patients randomized to receive a direct oral anticoagulant were significantly less likely to experience intracranial hemorrhage (HR = 0.38; CI, 0.26 to 0.56). There was minimal to moderate heterogeneity for most outcomes, although the measure used (I2) is unreliable with only four studies.

Study design: Meta-analysis (randomized controlled trials)

Funding source: Foundation

Setting: Outpatient (any)

Reference: Bennaghmouch N, de Veer AJWM, Bode K, et al. Efficacy and safety of the use of non-vitamin K antagonist oral anticoagulants in patients with nonvalvular atrial fibrillation and concomitant aspirin therapy: a meta-analysis of randomized trials. Circulation. 2018;137(11):1117–1129.

Editor's Note: Dr. Mark H. Ebell is Deputy Editor for Evidence-Based Medicine in AFP and cofounder and Editor-in-Chief of Essential Evidence Plus, published by Wiley-Blackwell, Inc. Dr. Allen F. Shaughnessy is an Assistant Medical Editor for AFP.


POEMs (patient-oriented evidence that matters) are provided by Essential Evidence Plus, a point-of-care clinical decision support system published by Wiley-Blackwell. For more information, see http://www.essentialevidenceplus.com. Copyright Wiley-Blackwell. Used with permission.

For definitions of levels of evidence used in POEMs, see http://www.essentialevidenceplus.com/product/ebm_loe.cfm?show=oxford.

To subscribe to a free podcast of these and other POEMs that appear in AFP, search in iTunes for “POEM of the Week” or go to http://goo.gl/3niWXb.

This series is coordinated by Sumi Sexton, MD, Editor-in-Chief.

A collection of POEMs published in AFP is available at https://www.aafp.org/afp/poems.



Want to use this article elsewhere? Get Permissions

More in AFP

Editor's Collections

Related Content

More in Pubmed


Nov 2021

Access the latest issue of American Family Physician

Read the Issue

Email Alerts

Don't miss a single issue. Sign up for the free AFP email table of contents.

Sign Up Now

Navigate this Article