title: Fiix-prothrombin time monitoring improves warfarin anticoagulation outcome in atrial fibrillation: a systematic review of randomized trials comparing Fiix-warfarin or direct oral anticoagulants to standard PT-warfarin.
abstract: BACKGROUND
  Monitoring warfarin with Fiix-prothrombin time (Fiix-PT), which is only affected by coagulation factors II and X, stabilizes anticoagulation and reduces thromboembolism compared to PT/INR monitoring. We compared outcome in nonvalvular atrial fibrillation (NVAF) patients treated with Fiix-warfarin, direct oral anticoagulants (DOACs), or PT-warfarin.
  
  
  METHODS
  A systematic efficacy and safety assessment by retrieving data from the Fiix trial and the four major phase III DOAC trials in NVAF. Prespecified outcomes included stroke and systemic embolism (SSE), SSE and myocardial infarction (MI), major bleeding (MB), composite major vascular events (SSEMI and MB; CMVE), and deaths. We calculated relative risk, 95% CI, and 95% confidence limits (CL) for each outcome and performed meta-analysis using fixed- and random-effects modeling.
  
  
  RESULTS
  There were 613 and 628 observation years with Fiix-warfarin and PT-warfarin in the Fiix trial, and 70 628 and 57 962 with DOACs and PT-warfarin in DOAC trials. Populations were comparable although death rates were lower in the Fiix trial. Compared to pooled PT-warfarin, Fiix-warfarin reduced SSE (RR 0.54;95% CI 0.26-1.10/95% CL <1.00), SSEMI (0.51;0.26-0.99/<0.90), MB (RR 0.63;0.37-1.07/<0.99), and CMVE (RR 0.66;0.43-1.00/<0.94). Vascular death was lower (RR 0.13;0.04-0.47/<0.42). Compared to pooled DOACs, Fiix-warfarin consistently had lower point estimates for the RR for efficacy and safety, but only significant for lower death rates (vascular death RR 0.14;0.04-0.49/<0.43). Meta-analysis comparing Fiix-warfarin and DOACs with PT-warfarin consistently found Fiix-warfarin to have the lowest point estimates for efficacy.
  
  
  CONCLUSIONS
  Monitoring warfarin with Fiix-PT reduces risk of vascular events in NVAF patients as much as DOACs. Warfarin monitored with Fiix-PT is an improved anticoagulant.
authors.affiliation: Landspitali National University Hospital of Iceland, Reykjavik, Iceland.|University of Iceland Faculty of Medicine, Reykjavik, Iceland.
authors.forename: P T
authors.initials: PT
authors.lastname: Onundarson
authors.affiliation: Landspitali National University Hospital of Iceland, Reykjavik, Iceland.
authors.forename: D O
authors.initials: DO
authors.lastname: Arnar
authors.affiliation: University of Iceland Faculty of Medicine, Reykjavik, Iceland.
authors.forename: S H
authors.initials: SH
authors.lastname: Lund
authors.affiliation: Landspitali National University Hospital of Iceland, Reykjavik, Iceland.
authors.forename: B R
authors.initials: BR
authors.lastname: Gudmundsdottir
authors.affiliation: University of Rochester Medical Center, Rochester, NY, USA.
authors.forename: C W
authors.initials: CW
authors.lastname: Francis
authors.affiliation: Landspitali National University Hospital of Iceland, Reykjavik, Iceland.
authors.forename: O S
authors.initials: OS
authors.lastname: Indridason
mesh_terms: D001281:Atrial Fibrillation / Q000150:complications / Q000401:mortality / Q000628:therapy*; D016903:Drug Monitoring / Q000379:methods*; D006801:Humans; D011517:Prothrombin Time; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome; D014652:Vascular Diseases / Q000517:prevention & control; D014859:Warfarin / Q000627:therapeutic use*
chemical_list: D014859:Warfarin
keywords: Rivaroxaban; apixaban; dabigatran; edoxaban; meta analysis; prothrombin time; systematic review; warfarin