title: 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.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Cardiology, Aalborg AF Study Group, Aalborg University Hospital, Aalborg, Denmark, pbn@rn.dk.
authors.forename: Peter Brønnum
authors.initials: PB
authors.lastname: Nielsen
authors.forename: Deirdre A
authors.initials: DA
authors.lastname: Lane
authors.forename: Lars Hvilsted
authors.initials: LH
authors.lastname: Rasmussen
authors.forename: Gregory Y H
authors.initials: GY
authors.lastname: Lip
authors.forename: Torben Bjerregaard
authors.initials: TB
authors.lastname: Larsen
mesh_terms: D000284:Administration, Oral; D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000188:drug therapy*; D002986:Clinical Trials as Topic; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D051437:Renal Insufficiency / Q000517:prevention & control*; D020521:Stroke / Q000517:prevention & control; D016896:Treatment Outcome; D014812:Vitamin K / Q000037:antagonists & inhibitors*; D014859:Warfarin / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000925:Anticoagulants; D014812:Vitamin K; D014859:Warfarin