New Oral Anticoagulants Poised to Alter Approach to AF
By Matthew E. Fink, MD
Professor and Chairman, Department of Neurology, Weill Cornell Medical College, and Neurologist-in-Chief, New York Presbyterian Hospital
This article originally appeared in the January 2014 issue of Neurology Alert. It was peer reviewed by M. Flint Beal, MD. Dr. Beal is Anne Parrish Titzel Professor, Department of Neurology and Neuroscience, Weill Cornell Medical Center. Dr. Fink is a retained consultant for MAQUET and Dr. Beal reports no financial relationships relevant to this field of study.
Source: Ruff CT, et al. Comparison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation: A meta-analysis of randomized trials. Lancet Neurology 2013; http://dx.doi.org/10.1016/S0140-6736(13)62343-0.
Four new oral anticoagulants (dabigatran, rivaroxaban, apixaban, and edoxaban) have been studied in individual clinical trials and, compared to warfarin, have been shown to be equal or better in the prevention of cardioembolic stroke in the setting of atrial fibrillation, with a reduced frequency of intracranial bleeding.1-4
Ruff and colleagues performed a meta-analysis of Phase 3, randomized trials in patients with atrial fibrillation, comparing all four of these new anticoagulants with warfarin, and analyzed outcomes in 71,683 participants in four trials. The main outcomes studied were stroke and systemic embolic events, ischemic stroke, hemorrhagic stroke, all-cause mortality, myocardial infarction, major bleeding, intracranial hemorrhage, and gastrointestinal hemorrhage, and the authors calculated relative risks (RRs) and 95% confidence intervals for each outcome.
In this analysis pooling data from only the Phase 3 randomized trial for each of these four agents, new oral anticoagulants significantly reduced stroke or systemic embolism by 19% compared to warfarin (RR=0.81), driven primarily by a reduction in hemorrhagic stroke, and also resulted in a reduction in all-cause mortality (RR = 0.90), with an increase in gastrointestinal hemorrhage. These new medications had a favorable risk-benefit profile, with significant reductions in stroke, intracranial hemorrhage, and mortality, with a similar rate of major bleeding as for warfarin.
- Connolly SJ, et al. Dabigatran versus warfarin in patients with atrial fibrillation. N Engl J Med 2009;361:1139-1151.
- Patel MR, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med 2011;365:883-891.
- Granger CB, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2011;365:981-992.
- Giugliano RP, et al. Edoxaban versus warfarin in patients with atrial fibrillation. N Engl J Med 2013;369:2093-2104.