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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Colleges, School and Institutes


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.


Original languageEnglish
Pages (from-to)418-29
Number of pages12
JournalClinical Research in Cardiology
Issue number5
Publication statusPublished - May 2015


  • Administration, Oral, Anticoagulants, Atrial Fibrillation, Clinical Trials as Topic, Hemorrhage, Humans, Randomized Controlled Trials as Topic, Renal Insufficiency, Stroke, Treatment Outcome, Vitamin K, Warfarin