Finding a safer alternative for warfarin for the long-term management of patients with atrial fibrillation (AF) has been the major area of interest for many clinicians and researchers.
Currently, there are a couple of potential alternatives to warfarin in selected patients. The available three drugs fall into two categories: direct thrombin inhibitor (dabigatran) and factor Xa inhibitors (rivaroxaban and apixaban). A recent systematic review1 and meta-analysis of randomized clinical trials was published to help answer the question of which oral anticoagulant can take the throne from warfarin?
The systematic review compared the new three oral anticoagulants (apixaban, dabigatran, and rivaroxaban) to warfarin in terms of efficacy and safety in the management of patients with AF. Only three trials, with duration of more than 1 year and including 44,563 patients, met the inclusion criteria. The three included trials assessed the safety and efficacy of the new oral anticoagulant Apixaban (ARISTOTLE), dabigatran (RE-LY), and rivaroxaban (ROCKET AF).
When compared to warfarin, the new oral anticoagulants were associated with reduced risk of all-cause stroke and systemic embolism (relative risk RR 0.78; 95% 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); vascular mortality (RR 0.87; 95% CI 0.77 to 0.98); and intracranial bleeding (RR 0.49; 95% CI 0.36 to 0.66). However, there was no statistically significant difference between the two groups in risk of major bleeding (RR 0.88; 95% CI 0.71 to 1.09) or gastrointestinal bleeding (RR 1.25; 95% CI 0.91 to 1.72).
The authors concluded that the new oral anticoagulants are more efficacious than warfarin in preventing stroke or systemic embolism in patients with AF, with a lower risk of intracranial bleeding and possible lower major bleeding risk. However, the risk of gastrointestinal bleeding associated with the new agents is higher.
The authors advocate using the new oral anticoagulants over warfarin for the management of patients with AF. Although these agents seem to be promising, long term safety remains an issue. Also, the authors did not include post-marketing surveillance reports2 which could change our opinion about how fast can we adopt these new kids on the block. Another major concern is the lack of a specific antidote to reverse their anticoagulation effect.
It is great to have a safer and more efficacious alternative for warfarin, however, our quest to retire warfarin blind our eyes on seeing the alternatives pitfalls. Perhaps we may not have the perfect candidate, but we need the safest one.
1. Miller CS, Grandi SM, Shimony A, et al. Meta-Analysis of Efficacy and Safety of New Oral Anticoagulants (Dabigatran, Rivaroxaban, Apixaban) Versus Warfarin in Patients With Atrial Fibrillation. Am J Cardiol 2012 Apr 24. [Epub ahead of print]
2. FDA Drug Safety Communication: Safety review of post-market reports of serious bleeding ...