title: Consistency of safety and efficacy of new oral anticoagulants across subgroups of patients with atrial fibrillation.
abstract: OBJECTIVE
  The well-known limitations of vitamin K antagonists (VKA) led to development of new oral anticoagulants (NOAC) in non-valvular atrial fibrillation (NVAF). The aim of this meta-analysis was to determine the consistency of treatment effects of NOAC irrespective of age, comorbidities, or prior VKA exposure.
  
  
  RESULTS
  All randomized, controlled phase III trials comparing NOAC to VKA up to October 2012 were eligible provided their results (stroke/systemic embolism (SSE) and major bleeding (MB)) were reported according to age (≤ or >75 years), renal function, CHADS2 score, presence of diabetes mellitus or heart failure, prior VKA use or previous cerebrovascular events. Interactions were considered significant at p <0.05. Three studies (50,578 patients) were included, respectively evaluating apixaban, rivaroxaban, and dabigatran versus warfarin. A trend towards interaction with heart failure (p = 0.08) was observed with respect to SSE reduction, this being greater in patients not presenting heart failure (RR = 0.76 [0.67-0.86]) than in those with heart failure (RR = 0.90 [0.78-1.04]); Significant interaction (p = 0.01) with CHADS2 score was observed, NOAC achieving a greater reduction in bleeding risk in patients with a score of 0-1 (RR 0.67 CI 0.57-0.79) than in those with a score ≥2 (RR 0.85 CI 0.74-0.98). Comparison of MB in patients with (RR 0.97 CI 0.79-1.18) and without (RR 0.76 CI 0.65-0.88) diabetes mellitus showed a similar trend (p = 0.06). No other interactions were found. All subgroups derived benefit from NOA in terms of SSE or MB reduction.
  
  
  CONCLUSIONS
  NOAC appeared to be more effective and safer than VKA in reducing SSE or MB irrespective of patient comorbidities. Thromboembolism risk, evaluated by CHADS2 score and, to a lesser extent, diabetes mellitus modified the treatment effects of NOAC without complete loss of benefit with respect to MB reduction.
authors.affiliation: Département de Médecine Interne et Vasculaire, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Université Claude Bernard Lyon 1, Lyon, France; Groupe de Recherche sur la Thrombose, EA3065, Université de Saint-Etienne, Jean Monnet, Saint-Etienne, France.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Lega
authors.affiliation: Groupe de Recherche sur la Thrombose, EA3065, Université de Saint-Etienne, Jean Monnet, Saint-Etienne, France; Département de Médecine Thérapeutique, Centre hospitalo-universitaire de Saint-Etienne, Hôpital Nord, Saint-Etienne, France; Inserm, CIE3, Saint-Etienne, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Bertoletti
authors.affiliation: Département de Médecine Thérapeutique, Centre hospitalo-universitaire de Saint-Etienne, Hôpital Nord, Saint-Etienne, France.
authors.forename: Cyrielle
authors.initials: C
authors.lastname: Gremillet
authors.affiliation: Inserm, CIE3, Saint-Etienne, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Chapelle
authors.affiliation: Groupe de Recherche sur la Thrombose, EA3065, Université de Saint-Etienne, Jean Monnet, Saint-Etienne, France; Département de Médecine Thérapeutique, Centre hospitalo-universitaire de Saint-Etienne, Hôpital Nord, Saint-Etienne, France; Inserm, CIE3, Saint-Etienne, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Mismetti
authors.affiliation: UMR CNRS 5558 Evaluation et Modélisation des Effets Thérapeutiques, Université Claude Bernard Lyon 1, Lyon, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Cucherat
authors.affiliation: Département de Médecine Interne et Vasculaire, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Université Claude Bernard Lyon 1, Lyon, France.
authors.forename: Denis
authors.initials: D
authors.lastname: Vital-Durand
authors.affiliation: Groupe de Recherche sur la Thrombose, EA3065, Université de Saint-Etienne, Jean Monnet, Saint-Etienne, France; Unité de Recherche Clinique, Innovation, Pharmacologie, Centre hospitalo-universitaire de Saint-Etienne, France.
authors.forename: Silvy
authors.initials: S
authors.lastname: Laporte
mesh_terms: D000284:Administration, Oral; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000188:drug therapy*; D017326:Clinical Trials, Phase III as Topic / Q000379:methods*; D006801:Humans; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D012449:Safety
chemical_list: D000925:Anticoagulants