Dabigatran, Rivaroxaban, or Apixaban versus Warfarin in Patients with Nonvalvular Atrial Fibrillation: A Systematic Review and Meta-Analysis of Subgroups.
Background. New oral anticoagulants (NOAC; rivaroxaban, dabigatran, apixaban) have become available as an alternative to warfarin anticoagulation in non-valvular atrial fibrillation (NVAF). Methods. MEDLINE and CENTRAL, regulatory agencies websites, clinical trials registers and conference proceedings were searched to identify randomised controlled trials of NOAC versus warfarin in NVAF. Two investigators reviewed all studies and extracted data on patient and study characteristics along with cardiovascular outcomes. Relative risks (RR) and 95% confidence intervals (CI) were estimated using a random effect meta-analysis. Results. Three clinical trials in 50,578 patients were included. The risk of non-hemorrhagic stroke and systemic embolic events (SEE) was similar with the NOAC and warfarin (RR = 0.93; 95% CI = 0.83-1.04), while the risk of intracranial bleeding (ICB) with the NOAC was lower than with warfarin (RR = 0.46; 95% CI = 0.33-0.65). We found differences in the effect size on all strokes and SEE depending on geographic region as well as on non-hemorrhagic stroke, SEE, bleeding and mortality depending on time in therapeutic range. Conclusion. The NOAC seem no more effective than warfarin for prevention of nonhemorrhagic stroke and SEE in the overall NVAF population, but are generally associated with a lower risk of ICB than warfarin.
Division of Pharmacology and Clinical Evaluation, Medicines for Human Use, Spanish Agency for Medicines and Medical Devices (AEMPS), c/Campezo 1, Edificio 8, 28022 Madrid, Spain.
Antonio
A
Gómez-Outes
Department of Clinical Pharmacology, Hospital Clínico San Carlos, c/Prof. Martín Lagos s/n, 28040 Madrid, Spain ; Department of Pharmacology, Universidad Complutense, Plaza Ramón y Cajal s/n, Ciudad Universitaria, 28040 Madrid, Spain.
Ana Isabel
AI
Terleira-Fernández
Department of Clinical Pharmacology, Hospital Clínic, University of Barcelona, c/Villarroel 170, 08036 Barcelona, Spain.
Gonzalo
G
Calvo-Rojas
Division of Pharmacology and Clinical Evaluation, Medicines for Human Use, Spanish Agency for Medicines and Medical Devices (AEMPS), c/Campezo 1, Edificio 8, 28022 Madrid, Spain.
M Luisa
ML
Suárez-Gea
Department of Clinical Pharmacology, Hospital Clínico San Carlos, c/Prof. Martín Lagos s/n, 28040 Madrid, Spain ; Department of Pharmacology, Universidad Complutense, Plaza Ramón y Cajal s/n, Ciudad Universitaria, 28040 Madrid, Spain.
Emilio
E
Vargas-Castrillón