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Comparative Study
. 2020 Jan-Dec:26:1076029619898764.
doi: 10.1177/1076029619898764.

A Systematic Review of Network Meta-Analyses and Real-World Evidence Comparing Apixaban and Rivaroxaban in Nonvalvular Atrial Fibrillation

Nathan R Hill  1 , Belinda Sandler  2 , Evelien Bergrath  3 , Dušan Milenković  3 , Ajibade O Ashaye  3 , Usman Farooqui  2 , Alexander T Cohen  4
Affiliations
Comparative Study

A Systematic Review of Network Meta-Analyses and Real-World Evidence Comparing Apixaban and Rivaroxaban in Nonvalvular Atrial Fibrillation

Nathan R Hill et al. Clin Appl Thromb Hemost. 2020 Jan-Dec.

Abstract

There is no direct evidence comparing the 2 most commonly prescribed direct oral anticoagulants, apixaban and rivaroxaban, used for stroke prevention in nonvalvular atrial fibrillation (NVAF). A number of network meta-analyses (NMAs) of randomized control trials and real-world evidence (RWE) studies comparing the efficacy, effectiveness, and safety of apixaban and rivaroxaban have been published; however, a comprehensive evidence review across the available body of evidence is lacking. In this study, we aimed to systematically review and evaluate the clinical outcomes of apixaban and rivaroxaban using a combination of data gleaned from both NMAs and RWE studies. The review identified 21 NMAs and 5 RWE studies. The data demonstrated that apixaban was associated with fewer major bleeding events compared to rivaroxaban. There was no difference in the efficacy/effectiveness profiles between these treatments. Bleeding is a serious complication of anticoagulation therapy for the management of NVAF, and is associated with increased rates of hospitalization, morbidity, mortality, and health-care expenditure. The majority of studies in this comprehensive evidence review suggests that apixaban has a lower risk of major bleeding events compared to rivaroxaban in patients with NVAF.

Keywords: apixaban; direct oral anticoagulants; major bleeding; nonvalvular atrial fibrillation; rivaroxaban; stroke; systematic review.

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Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: N. R. Hill, B. Sandler, and U. Farooqui are employees of Bristol-Myers Squibb Company. E. Bergrath and D. Milenković were employed by Evidera Inc, which provides consulting and research services to pharmaceutical, medical device, and related organizations, during the study and remain employed by Evidera Inc. A.O. Ashaye was employed by Evidera Inc during the study. In their salaried positions, Evidera employees work with a variety of companies and organizations and are precluded from receiving payment or honoraria directly for services rendered. D. Milenković also reports personal fees from UCL CRUK Cancer Trials Centre, during and outside the submitted work. A.T. Cohen reports grants and personal fees from Bristol-Myers Squibb Company and Pfizer Inc during the conduct of the study. Outside the submitted work, he reports personal fees from Boehringer Ingelheim, Johnson & Johnson, Portola, Sanofi, XO1, Janssen, and ONO Pharmaceuticals. He further reports grants and personal fees from Bristol-Myers Squibb Company, Daiichi-Sankyo Europe, Pfizer, Inc, and Bayer AG.

Figures

Figure 1.
Figure 1.
The PRISMA flow diagram of the systematic literature review. NMA indicates network meta-analysis; NVAF, nonvalvular atrial fibrillation; PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses; RWE, real-world evidence.
Figure 2.
Figure 2.
Risk of stroke or systemic embolism: apixaban vs rivaroxaban. Note: the dashed line separates NMA results (top) from RWE results (bottom). Network meta-analysis studies: apixaban dosing was 5 mg and rivaroxaban dosing was 20 mg unless indicated. For example, Lin 2015: rivaroxaban dosing was not reported; Ando 2017: rivaroxaban dosing was not reported. RWE studies: Noseworthy 2016: paper suggests that apixaban and rivaroxaban are a mixture of standard and (unspecified) reduced dosing; Deitelzweig 2017: apixaban dosing was 2.5 mg or 5 mg/rivaroxaban dosing was 10 mg, 15 mg, or 20 mg. ^Notable populations: NMA studies: Sardar 2013 (AF with previous stroke/transient ischemic attack); Lin 2015 (AF patients <65-74 and >75 years); Morimoto 2015 (chronic or paroxysmal AF); Nielsen 2015a: (patients with moderate renal impairment); Nielsen 2015b (patients with mild renal impairment); Katsanos 2016 (AF with previous stroke/ transient ischemic attack); Ando 2017 (AF in chronic kidney disease patients). RWE studies: Deitelzweig 2017 (≥65 years of age). *Main analysis (apixaban 2.5 mg or 5 mg); ** Dose sensitivity analysis (apixaban 5 mg [standard dose]). AF indicates atrial fibrillation; HR, hazard ratio; NR, not reported; NMA, network meta-analysis; OR, odds ratio; RR, risk ratio; RWE, real-world evidence.
Figure 3.
Figure 3.
Risk of major bleeding: apixaban vs rivaroxaban. Note: the dashed line separates NMA results (top) from RWE results (bottom). NMA studies: apixaban dosing was 5 mg and rivaroxaban dosing was 20 mg unless indicated. For example, Guo 2017: apixaban dosing was 5 mg or 10 mg, rivaroxaban was 15 mg or 20 mg; Biondi-Zoccai 2013: apixaban dosing was 2.5 mg or 5 mg; Assiri 2013: apixaban dosing was not reported. RWE studies: apixaban dosing was 2.5 mg or 5 mg and rivaroxaban dosing was 15 mg or 20 mg unless indicated. For example, Noseworthy 2016: paper suggests that apixaban and rivaroxaban are a mixture of standard and (unspecified) reduced dosing; Deitelzweig 2017: rivaroxaban dosing was 10 mg, 15 mg, or 20 mg; Adeboyeje 2016/17: apixaban and rivaroxaban dosing was not reported. ^Notable populations: NMA studies: Sardar 2013 (AF with previous stroke/transient ischemic attack); Lin 2015 (AF patients <65-74 and >75 years); Morimoto 2015 (chronic or paroxysmal AF); Nielsen 2015a: (patients with moderate renal impairment); Nielsen 2015b (patients with mild renal impairment); Katsanos 2016 (AF with previous stroke/transient ischemic attack); Ando 2017 (AF in chronic kidney disease patients). RWE studies: Deitelzweig 2017 (≥65 years of age). *Main analysis (apixaban 2.5 mg or 5 mg); ** Dose sensitivity analysis (apixaban 5 mg [standard dose]). AF indicates atrial fibrillation; HR, hazard ratio; NMA, network meta-analysis; OR, odds ratio; RR, risk ratio; RWE, real-world evidence.
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