title: New oral anticoagulants and the risk of intracranial hemorrhage: traditional and Bayesian meta-analysis and mixed treatment comparison of randomized trials of new oral anticoagulants in atrial fibrillation.
abstract: OBJECTIVE
  Randomized studies have shown a decreased risk of intracranial hemorrhage (ICH) with use of novel oral anticoagulants (NOACs). However, it is unclear whether the magnitude of benefit is similar for all NOACs currently available.
  
  
  OBJECTIVE
  To perform a systematic review and meta-analysis to quantitatively assess the rates of ICH within the framework of both conventional and Bayesian statistics.
  
  
  METHODS
  The MEDLINE, CENTRAL, CINAHL, and EBSCO databases, supplemented with conference abstracts, were searched up to December 1, 2012, with no language restriction.
  
  
  METHODS
  Randomized trials comparing NOACs vs a comparator and reporting on ICH events.
  
  
  METHODS
  The NOACs were pooled to perform a comparison with all comparators and among themselves in both traditional frequentist and Bayesian random-effects models using vague priors and Markov chain Monte Carlo simulation with Gibbs sampling, calculating pooled odds ratios and associated 95% confidence intervals as well as numbers needed to treat and 95% credible intervals for the Bayesian analysis.
  
  
  METHODS
  Intracranial hemorrhage events associated with NOACs in comparison with comparators, expressed as odds ratios.
  
  
  RESULTS
  Six studies (1 administering dabigatran etexilate mesylate, 2 administering rivaroxaban, and 3 administering apixaban) enrolling a total of 57,491 patients were included for analysis. The NOACs significantly reduced the risk of ICH against all comparators (odds ratio = 0.49; 95% CI, 0.36-0.65). Each of the 3 drugs reduced the risk of ICH, with Bayesian indirect comparison analysis not revealing a significant credible difference between the specific medications.
  
  
  CONCLUSIONS
  Novel oral anticoagulants are uniformly associated with an overall reduced risk of ICH when used for stroke prevention in atrial fibrillation. Any of the currently available NOACs can be considered first line for patients at high risk for ICH.
authors.affiliation: Division of Cardiology, Brown University, Providence, Rhode Island.
authors.forename: Saurav
authors.initials: S
authors.lastname: Chatterjee
authors.affiliation: Department of Medicine, New York Medical College-Metropolitan Hospital Center, New York.
authors.forename: Partha
authors.initials: P
authors.lastname: Sardar
authors.affiliation: Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Biondi-Zoccai
authors.affiliation: Division of Cardiology, University of Texas Southwestern Medical Center, Dallas.
authors.forename: Dharam J
authors.initials: DJ
authors.lastname: Kumbhani
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000925:Anticoagulants / Q000008:administration & dosage / Q000009:adverse effects*; D001281:Atrial Fibrillation / Q000188:drug therapy*; D001499:Bayes Theorem; D004311:Double-Blind Method; D006801:Humans; D020300:Intracranial Hemorrhages / Q000139:chemically induced*; D016239:MEDLINE / Q000706:statistics & numerical data; D016032:Randomized Controlled Trials as Topic
chemical_list: D000925:Anticoagulants