Direct acting oral anticoagulants (DOACs), especially cost-effective apixaban, prevent strokes better than warfarin in patients with atrial fibrillation, according to a study in the BMJ.

José A López-López, PhD, of the Department of Population Health Sciences at Bristol Medical School at the University of Bristol, UK, and associates compared the health, cost, and safety effects of DOACs with warfarin in patients with atrial fibrillation.

The researchers conducted 23 randomized trials with 94,656 atrial fibrillation patients (median age, 70) focusing on the effects of 3 direct factor Xa inhibitors and 1 direct factor II inhibitor. Treatment ranged from 3 to 30 months. Apixaban (5 mg twice daily), dabigatran (150 mg twice daily), edoxaban (60 mg once daily), and rivaroxaban (20 mg once daily) were compared with warfarin and each other to assess associated health risks and stroke prevention, as well as drug cost-effectiveness.

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Compared with warfarin, apixaban (odds ratio [OR], 0.79), dabigatran (OR, 0.65), edoxaban (OR, 0.86), and rivaroxaban (OR, 0.88) all reduced stroke or systemic embolism risks. The authors noted that stroke or systemic embolism risks were greater in patients taking edoxaban (OR, 1.33) and rivaroxaban (OR, 1.35) compared with dabigatran.

When compared with warfarin, all 4 non-vitamin K antagonists reduced bleeding risks, although bleeding risks were higher in patients taking dabigatran 150 mg twice daily or rivaroxaban 20 mg once daily than in patients taking apixaban 5 mg once daily.

Using DOACs compared with warfarin reduced all-cause mortality risk and major intracranial bleeding risks but increased gastrointestinal bleeding in patients with atrial fibrillation.

The cost effectiveness analysis, which was measured using the assumption that the UK NHS would pay £20,000 for each year of perfect health, resulted in all DOACs rating higher than warfarin. The highest estimated quality adjusted life years (QALYs) and incremental net benefit were noted in patients who were administered apixaban (5.49 years and £7533, respectively) and lowest in patients taking edoxaban (5.41 years, £5212).

Apixaban was the highest ranking drug with the most positive outcomes of the DOACs compared with warfarin, which the researchers hope will contribute to future clinical applications.

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“Policy makers, healthcare providers, and patients could therefore consider apixaban to be the first choice among DOACs for the prevention of stroke in most patients with atrial fibrillation, based on currently available evidence,” the authors wrote.

“This approach should increase the use of this drug class, benefit patient safety, and lead to eventual cost savings.”


  1. López-López JA, Sterne JAC, Thom HHZ, et al. Oral anticoagulants for prevention of stroke in atrial fibrillation: systemic review, network meta-analysis, and cost effectiveness analysis. BMJ. 2017 Nov 28. doi: 10.1136/bmj.j5058