title: Non-Vitamin K Antagonist Oral Anticoagulants in Patients With Atrial Fibrillation and Valvular Heart Disease.
abstract: BACKGROUND
  Valvular heart disease (VHD) and atrial fibrillation (AF) often coexist. Phase III trials comparing non-vitamin K antagonist oral anticoagulants (NOACs) with warfarin excluded patients with moderate/severe mitral stenosis or mechanical heart valves, but variably included patients with other VHD and valve surgeries.
  
  
  OBJECTIVE
  This study aimed to determine relative safety and efficacy of NOACs in patients with VHD.
  
  
  METHODS
  We performed a meta-analysis of the 4 phase III AF trials of the currently available NOACs versus warfarin in patients with coexisting VHD to assess pooled estimates of relative risk (RR) and 95% confidence intervals (CIs) for stroke/systemic embolic events (SSEE), major bleeding, intracranial hemorrhage (ICH), and all-cause death.
  
  
  RESULTS
  Compared with warfarin, the rate of SSEE in patients treated with higher-dose NOACs was lower and consistent among 13,585 patients with (RR: 0.70; 95% CI: 0.58 to 0.86) or 58,098 without VHD (RR: 0.84; 95% CI: 0.75 to 0.95; interaction p = 0.13). Major bleeding in patients on higher-dose NOACs versus warfarin was similar and consistent among patients with (RR: 0.93; 95% CI: 0.68 to 1.27) or without VHD (RR: 0.85; 95% CI: 0.70 to 1.02; interaction p = 0.63 for VHD/no-VHD difference). Intracranial hemorrhage was lower with higher-dose NOACs than with warfarin irrespective of VHD (RR: 0.47; 95% CI: 0.24 to 0.93, and 0.49; 95% CI: 0.41 to 059, respectively; interaction p = 0.91). No protective effect of higher-dose NOACs in preventing all-cause death seemed to be present in patients with VHD versus without VHD (RR:1.01; 95% CI: 0.90 to 1.14 vs. RR: 0.88; 95% CI: 0.82 to 0.94, respectively; interaction p = 0.03).
  
  
  CONCLUSIONS
  High-dose NOACs provide overall efficacy and safety similar in AF patients with or without VHD.
authors.affiliation: Institute of Cardiology and Center of Excellence on Aging, "G. d'Annunzio" University, Chieti, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Renda
authors.affiliation: Institute of Cardiology and Center of Excellence on Aging, "G. d'Annunzio" University, Chieti, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Ricci
authors.affiliation: Division of Cardiovascular Medicine, Brigham and Women's Hospital, TIMI Study Group, Boston, Massachusetts. Electronic address: rgiugliano@partners.org.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Giugliano
authors.affiliation: Institute of Cardiology and Center of Excellence on Aging, "G. d'Annunzio" University, Chieti, Italy. Electronic address: rdecater@unich.it.
authors.forename: Raffaele
authors.initials: R
authors.lastname: De Caterina
mesh_terms: D000925:Anticoagulants / Q000494:pharmacology / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000150:complications*; D006349:Heart Valve Diseases / Q000150:complications*; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D020521:Stroke / Q000517:prevention & control*; D014812:Vitamin K / Q000037:antagonists & inhibitors*
chemical_list: D000925:Anticoagulants; D014812:Vitamin K
keywords: atrial fibrillation; bleeding; death; major bleeding; stroke; systemic embolism; valvular heart disease