Effectiveness and Safety of Rivaroxaban 15 or 20 mg Versus Vitamin K Antagonists in Nonvalvular Atrial Fibrillation

Patrick Blin, Laurent Fauchier, Caroline Dureau-Pournin, Frédéric Sacher, Jean Dallongeville, Marie-Agnès Bernard, Regis Lassalle, Cécile Droz-Perroteau, Nicholas Moore, Patrick Blin, Laurent Fauchier, Caroline Dureau-Pournin, Frédéric Sacher, Jean Dallongeville, Marie-Agnès Bernard, Regis Lassalle, Cécile Droz-Perroteau, Nicholas Moore

Abstract

Background and Purpose- We compared the 1-year safety and effectiveness of rivaroxaban 15 mg (R15) or rivaroxaban 20 mg (R20) to vitamin K antagonists (VKAs) in patients with nonvalvular atrial fibrillation. Methods- New user cohort study of patients dispensed R15 or R20 versus VKA in 2013 or 2014 for nonvalvular atrial fibrillation, followed 1 year in the French Système National des Données de Santé (66 million people). R15 and R20 users were matched 1:1 with VKA users on sex, age, date of first drug dispensing, and high-dimensional propensity score. Hazard ratios (95% CIs) for stroke and systemic embolism, major bleeding, and death were computed using Cox proportional hazards or models by Fine and Gray during exposure. Results- In 31 171 matched R20 and VKA, mean age, 71; 62% men; 76% with CHA2DS2-VASc ≥2; 5% HAS-BLED >3 (hypertension, abnormal renal and liver function, stroke, bleeding, labile INR, elderly, drugs or alcohol); incidence rates for stroke and systemic embolism were 1.5% and 1.9% (hazard ratio, 0.79 [0.69-0.90]); major bleeding, 1.5% and 2.2% (0.67 [0.59-0.77]); death, 3.9% and 5.8% (0.67 [0.61-0.73]). In 23 314 matched R15 and VKA patients, mean age, 80; 47% men; 93% with CHA2DS2-VASc ≥2 and 9% with HAS-BLED >3; incidence rates of stroke and systemic embolism were 2.3% and 2.1% (1.05 [0.92-1.21]); major bleeding, 2.4% and 2.9% (0.84 [0.74-0.96]); death, 9.1% and 10.8% (0.85 [0.79-0.90]). Numbers needed to treat to observe one fewer death (NNT) were 46 for R15 and 61 for R20. Conclusions- In real life in France over 2013 to 2015, R15 and R20 were at least as effective and safer than VKA. Clinical Trial Registration- URL: http://www.encepp.eu. Unique identifier: EUPAS14567.

Keywords: France; atrial fibrillation; humans; pharmacoepidemiology; rivaroxaban.

Figures

Figure 1.
Figure 1.
Patient disposition. DOAC indicates direct-acting oral anticoagulant; NVAF, nonvalvular atrial fibrillation; and VKA, vitamin K antagonist.
Figure 2.
Figure 2.
Effectiveness and safety outcomes in rivaroxaban 20 mg (R20) vs vitamin K antagonist (VKA) patients: forest plots. HR indicates hazard ratio.
Figure 3.
Figure 3.
Effectiveness and safety outcomes in rivaroxaban 15 mg (R15) vs vitamin K antagonist (VKA) patients: forest plots. HR indicates hazard ratio.

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