Physicians' Academy for Cardiovascular Education

New oral anticoagulants vs warfarin in patients with AF

Literature - Miller SC et al. Am J Cardiol 2012

Meta-Analysis of Efficacy and Safety of New Oral Anticoagulants (Dabigatran, Rivaroxaban, Apixaban) Versus Warfarin in Patients With Atrial Fibrillation.


Miller CS, Grandi SM, Shimony A, Filion KB, Eisenberg MJ.
Am J Cardiol. 2012 Apr 24. [Epub ahead of print]


Background

The long-term use of new oral anticoagulants has been evaluated in 3 large phase III randomized controlled trials, the Apixaban for Reduction of Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial,[1] the Randomized Evaluation of Long-Term Anticoagulation Therapy (RELY) trial,[2] and the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF)[3]. This meta-analysis examined the long-term efficacy and safety of the new oral anticoagulants compared to warfarin in preventing stroke and systemic embolism in patients with atrial fibrillation.


Main results

  • The new oral anticoagulants were found to be at least noninferior to warfarin for the composite end point of stroke (including hemorrhagic stroke) and systemic embolism (22% RR reduction).
  • All 3 drugs were associated with a significantly decreased risk for hemorrhagic stroke compared to warfarin (fig. 1, 55% RR reduction).
  • Dabigatran and rivaroxaban were found to have comparable risks for major bleeding to warfarin, while apixaban demonstrated superiority for this outcome; gastrointestinal bleedings were heterogenous.
  • The new oral anticoagulants were each associated with a decreased risk for intracranial bleeding compared to warfarin (51% RR reduction).

Forest plot for:
  - all-cause stroke and systemic embolism
  - ischemic and unspecified stroke, and
  - hemorrhagic stroke,

new oral anticoagulants (NOA) versus warfarin in patients with AF

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Conclusion

The new oral anticoagulants are more efficacious than warfarin in preventing stroke and systemic embolism in patients with AF, with a favourable decreased risk of intracranial bleeding.

References

1. Granger CB, Alexander JH, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2011;365:981–992.
2. Connolly SJ, Ezekowitz MD, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009;361:1139 –1151.
3. Patel MR, Mahaffey KW, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011; 365:883– 891.


Abstract

New oral anticoagulants, including apixaban, dabigatran, and rivaroxaban, have been developed as alternatives to warfarin, the standard oral anticoagulation therapy for patients with atrial fibrillation (AF). A systematic review and meta-analysis of randomized controlled trials was performed to compare the efficacy and safety of new oral anticoagulants to those of warfarin in patients with AF. The published research was systematically searched for randomized controlled trials of >1 year in duration that compared new oral anticoagulants to warfarin in patients with AF. Random-effects models were used to pool efficacy and safety data across randomized controlled trials. Three studies, including 44,563 patients, were identified. Patients randomized to new oral anticoagulants had a decreased risk for all-cause stroke and systemic embolism (relative risk [RR] 0.78, 95% confidence interval [CI] 0.67 to 0.92), ischemic and unidentified stroke (RR 0.87, 95% CI 0.77 to 0.99), hemorrhagic stroke (RR 0.45, 95% CI 0.31 to 0.68), all-cause mortality (RR 0.88, 95% CI 0.82 to 0.95), and vascular mortality (RR 0.87, 95% CI 0.77 to 0.98). Randomization to a new oral anticoagulant was associated with a lower risk for intracranial bleeding (RR 0.49, 95% CI 0.36 to 0.66). Data regarding the risks for major bleeding (RR 0.88, 95% CI 0.71 to 1.09) and gastrointestinal bleeding (RR 1.25, 95% CI 0.91 to 1.72) were inconclusive. In conclusion, the new oral anticoagulants are more efficacious than warfarin for the prevention of stroke and systemic embolism in patients with AF. With a decreased risk for intracranial bleeding, they appear to have a favorable safety profile, making them promising alternatives to warfarin.

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