Direct oral anticoagulants for stroke prevention in atrial fibrillation: treatment outcomes and dosing in special populations

Abstract

Background: To review data from the pivotal phase III trials evaluating the efficacy and safety of direct oral anticoagulants (DOACs) versus warfarin for stroke prevention in patients with nonvalvular atrial fibrillation (NVAF), and to summarize the major findings with regards to patient subgroups that are at an increased risk for stroke or bleeding.

Methods: A PubMed literature search (January 2009 to January 2017) was performed using the terms 'dabigatran', 'rivaroxaban', 'apixaban', 'edoxaban', 'atrial fibrillation', 'RE-LY', 'ROCKET AF', 'ARISTOTLE', and 'ENGAGE AF-TIMI 48'. All primary publications and secondary analyses in special populations at increased risk of stroke or bleeding from the pivotal phase III clinical trials were evaluated.

Results: Available secondary analyses indicate no treatment interactions with regards to stroke or systemic embolic event (SEE) prevention for any of the DOACs in the patient subgroups, including patients with advanced age, impaired renal function, diabetes, prior stroke, concomitant antiplatelet therapy, heart failure, prior stroke, history of hypertension, myocardial infarction (MI), coronary artery disease, and peripheral artery disease (PAD). Although higher bleeding incidence was reported with dabigatran and rivaroxaban in patients aged 75 years and over with apixaban in patients with diabetes, and with rivaroxaban in patients with previous MI or PAD, no changes in dosing are recommended.

Conclusions: Overall, results of secondary analyses indicate that the recommended dosing strategy for each of the DOACs produces a consistent anticoagulant effect across a diverse patient population, including those at increased risk of stroke or bleeding.

Keywords: direct oral anticoagulants; dosing recommendations; nonvalvular atrial fibrillation; special populations; stroke prevention.

Figure 1.

Treatment outcomes in special populations. (a) Dabigatran 150 mg versus warfarin, (b) rivaroxaban versus warfarin, (c) apixaban versus warfarin, and (d) higher-dose edoxaban versus warfarin. ASA, aspirin; Biv, biventricular; CAD, coronary artery disease; CI, confidence interval; CrCL, creatinine clearance; CRNM, clinically relevant nonmajor bleeding; eGFR, estimated glomerular filtration rate; HF, heart failure; HR, hazard ratio; ICD, implantable cardioverter defibrillator; LVEF, left ventricular ejection fraction; LVSD, left ventricular systolic dysfunction; MI, myocardial infarction; NYHA, New York Heart Association; PAD, peripheral artery disease; PEF, preserved ejection fraction; SEE, systemic embolism; TIA, transient ischemic attack.