Comparative effectiveness and safety of non-vitamin K antagonist oral anticoagulants and warfarin in patients with atrial fibrillation: propensity weighted nationwide cohort study.
To study the effectiveness and safety of the non-vitamin K antagonist oral anticoagulants (novel oral anticoagulants, NOACs) dabigatran, rivaroxaban, and apixaban compared with warfarin in anticoagulant naïve patients with atrial fibrillation.
Observational nationwide cohort study.
Three Danish nationwide databases, August 2011 to October 2015.
61?678 patients with non-valvular atrial fibrillation who were naïve to oral anticoagulants and had no previous indication for valvular atrial fibrillation or venous thromboembolism. The study population was distributed according to treatment type: warfarin (n=35?436, 57%), dabigatran 150 mg (n=12?701, 21%), rivaroxaban 20 mg (n=7192, 12%), and apixaban 5 mg (n=6349, 10%).
Effectiveness outcomes defined a priori were ischaemic stroke; a composite of ischaemic stroke or systemic embolism; death; and a composite of ischaemic stroke, systemic embolism, or death. Safety outcomes were any bleeding, intracranial bleeding, and major bleeding.
When the analysis was restricted to ischaemic stroke, NOACs were not significantly different from warfarin. During one year follow-up, rivaroxaban was associated with lower annual rates of ischaemic stroke or systemic embolism (3.0% v 3.3%, respectively) compared with warfarin: hazard ratio 0.83 (95% confidence interval 0.69 to 0.99). The hazard ratios for dabigatran and apixaban (2.8% and 4.9% annually, respectively) were non-significant compared with warfarin. The annual risk of death was significantly lower with apixaban (5.2%) and dabigatran (2.7%) (0.65, 0.56 to 0.75 and 0.63, 0.48 to 0.82, respectively) compared with warfarin (8.5%), but not with rivaroxaban (7.7%). For the combined endpoint of any bleeding, annual rates for apixaban (3.3%) and dabigatran (2.4%) were significantly lower than for warfarin (5.0%) (0.62, 0.51 to 0.74). Warfarin and rivaroxaban had comparable annual bleeding rates (5.3%).
All NOACs seem to be safe and effective alternatives to warfarin in a routine care setting. No significant difference was found between NOACs and warfarin for ischaemic stroke. The risks of death, any bleeding, or major bleeding were significantly lower for apixaban and dabigatran compared with warfarin.
Notes
Cites: Europace. 2012 Oct;14(10):1385-41322923145
Cites: Stroke. 2015 Sep;46(9):2555-6126304863
Cites: Thromb Haemost. 2014 May 5;111(5):789-9724500243
Cites: Ann Intern Med. 2007 Jun 19;146(12):857-6717577005
Cites: J Intern Med. 2015 Jul;278(1):1-1825758241
Cites: N Engl J Med. 2013 Nov 28;369(22):2093-10424251359
Cites: Scand J Public Health. 2011 Jul;39(7 Suppl):22-521775345
Cites: Am Heart J. 2010 Oct;160(4):635-4120934556
Cites: Stat Med. 1999 Mar 30;18(6):695-70610204198