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Renal function and non-vitamin K oral anticoagulants in comparison with warfarin on safety and efficacy outcomes in atrial fibrillation patients: a systemic review and meta-regression analysis

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Abstract

Objective

To investigate the relative effect of warfarin versus non-vitamin K oral anticoagulants (NOACs) in thrombotic and bleeding outcomes in subgroups of atrial fibrillation (AF) patients with varying degrees of renal dysfunction.

Methods

Systemic review and meta-regression analyses on NOACs versus warfarin, supplemented with indirect comparisons were conducted. The eligibility criteria for inclusion were randomised controlled trials comparing NOACs against warfarin for stroke prevention in AF patients. Outcomes of interest were stroke or systemic embolism (SE) and major bleeding.

Results

Five studies comprising 72,845 AF patients randomised to either a NOAC or warfarin were included in the meta-regression analysis. A shift in strata from no renal impairment to renal impairment resulted in a non-significant impact on bleeding and stroke/SE, indicating similar safety and efficacy, despite renal function status. Apixaban was associated with less major bleeding compared to dabigatran and rivaroxaban but not edoxaban in patients with moderate renal impairment. For efficacy outcomes, only dabigatran 150 mg was statistically significantly favoured compared to edoxaban 30 mg. For efficacy outcomes in mild renal impairment, both dabigatran 150 mg and rivaroxaban 10 mg (J-ROCKET) were statistically significantly favoured against edoxaban 30 mg.

Conclusion

Non-vitamin K oral anticoagulants had similar efficacy and safety compared to warfarin across different levels of renal function. Indirect comparisons suggest that apixaban and edoxaban were associated with a better safety profile in patients with moderate renal impairment. However, caution is warranted when interpreting indirect comparisons of drugs investigated in different trials. Prescribers should fit the most appropriate NOAC to the AF patient characteristics (and vice versa) to individualise effective stroke prevention.

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Conflict of interest

The study received financial support by an unrestricted grant from The Obel Family Foundation. DAL has received investigator initiated educational grants from Bayer Healthcare and Boehringer Ingelheim and served as a speaker for Boehringer Ingelheim, Bayer Healthcare, BMS/Pfizer. In addition, DAL is on the Steering Committee of a Phase IV apixaban study (AEGEAN) and was a panellist on the 9th edition of the American College of Chest Physicians guidelines on antithrombotic therapy in AF. GYHL has served as a consultant for Bayer, Astellas, Merck, Sanofi, Bristol-Myers Squibb/Pfizer, Daiichi-Sankyo, Biotronik, Portola, and Boehringer Ingelheim, and as a speaker for Bayer, Bristol-Myers Squibb/Pfizer, Boehringer Ingelheim, Daiichi-Sankyo, and Sanofi-Aventis. LHR has been on the speakers’ bureaus of Bayer, BMS/Pfizer and Boehringer Ingelheim. TBL has been an investigator for Janssen Scientific Affairs and Boehringer Ingelheim, and served on speaker bureaux for Bayer, Bristol-Myers Squibb/Pfizer, Janssen Pharmaceuticals, Takeda, Roche Diagnostics, and Boehringer Ingelheim. PBN: none declared.

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Correspondence to Peter Brønnum Nielsen.

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G. Y. H. Lip and T. B. Larsen are joint senior authors.

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Nielsen, P.B., Lane, D.A., Rasmussen, L.H. et al. Renal function and non-vitamin K oral anticoagulants in comparison with warfarin on safety and efficacy outcomes in atrial fibrillation patients: a systemic review and meta-regression analysis. Clin Res Cardiol 104, 418–429 (2015). https://doi.org/10.1007/s00392-014-0797-9

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  • DOI: https://doi.org/10.1007/s00392-014-0797-9

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