Meta-analysis compares treatments for stroke prevention in afib

Apixaban, 5 mg twice daily, performed best for most outcomes in patients with atrial fibrillation in a new meta-analysis.

Researchers analyzed published randomized controlled trials that evaluated the use of a direct-acting oral anticoagulant (DOAC) (apixaban, betrixaban, edoxaban, rivaroxaban, or dabigatran), a vitamin K antagonist, or an antiplatelet drug to help prevent stroke in patients with atrial fibrillation. Efficacy, safety, and cost-effectiveness were compared. The study results were published online Nov. 28 by BMJ.

Overall, 23 randomized phase II or phase III trials involving a total of 94,656 patients were included in the analysis. Sixteen trials were phase III trials, involving 97% of the patients. Thirteen trials examined apixaban, betrixaban, dabigatran, edoxaban, or rivaroxaban versus warfarin, with treatment durations ranging from three to 30 months. All of the trials involving DOACs and two additional trials were funded by pharmaceutical companies.

Risk for stroke or systemic embolism was lower with apixaban (5 mg twice daily), dabigatran (150 mg twice daily), edoxaban (60 mg twice daily), and rivaroxaban (20 mg twice daily) than warfarin. Dabigatran, 150 mg twice daily, was associated with a lower risk for stroke or systemic embolism than edoxaban, 60 mg once daily, or rivaroxaban, 20 mg once daily. Risk for all-cause mortality was lower for all DOACs than for warfarin, and apixaban (5 mg twice daily), dabigatran (110 mg twice daily), and edoxaban (30 mg or 60 mg twice daily) were all associated with a lower major bleeding risk than warfarin.

Among DOACs, risk for major bleeding was lower with dabigatran, 150 mg twice daily, or rivaroxaban, 20 mg twice daily, than with apixaban, 5 mg twice daily. Rivaroxaban, 20 mg twice daily, was also associated with lower risk than edoxaban, 60 mg once daily. Most DOACs were associated with a substantially lower risk for intracranial bleeding than warfarin, but some DOACs were associated with a higher risk for gastrointestinal bleeding. In cost-effectiveness analyses, apixaban, 5 mg twice daily, appeared likely to be cost-effective versus warfarin.

The authors noted that some outcomes were not reported completely, that the patients treated in the included trials may not represent those treated in clinical practice, and that more information is needed on the long-term safety of DOACs, among other limitations. However, they concluded that DOACs and warfarin appear to be equally effective for stroke prevention in patients with atrial fibrillation and that DOACs have a lower risk for bleeding.

“Our analysis indicates that, of the currently available DOACs, apixaban ranks highest on the balance of efficacy, safety, and cost. 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. They noted, however, that “clear guidance” is needed on DOAC hierarchy for stroke prevention and called for additional studies to help address this and other issues.

An accompanying editorial called the study up to date and comprehensive but said that these and similar findings should not be the only information considered when choosing anticoagulant therapy for nonvalvular atrial fibrillation. The editorialist stressed that some patients have contraindications to all DOACs and that treatment with warfarin remains effective. He also echoed the study authors' call for additional research.

“It's already clear that DOACs are at least as effective as warfarin, safer to use, and, of course, easier for patients. However, in transferring the new findings into practice, a pragmatic strategy of shared decision making that takes full account of patient-specific characteristics and preferences is more appropriate than following a blanket recommendation that one anticoagulant is best and should be prescribed over all others,” he wrote. “One anticoagulant may not fit all.”