title: Oral anticoagulation for pulmonary arterial hypertension: systematic review and meta-analysis.
abstract: BACKGROUND
  Uncertainty exists about the benefit of oral anticoagulation in the treatment of pulmonary arterial hypertension (PAH), which is a lethal disease. We aimed to review and quantify the effect of oral anticoagulants in overall survival of PAH patients.
  
  
  METHODS
  We searched for randomized and observational studies that evaluated oral anticoagulants in PAH in the electronic databases MEDLINE, CENTRAL and ISI Web of Knowledge (December 2013). Review articles and references were also screened. We performed a random effects meta-analysis to estimate pooled HRs and 95% confidence intervals. Statistical heterogeneity was evaluated using the I(2) test.
  
  
  RESULTS
  No randomized controlled trials were identified. Nine cohort studies (2 prospective and 7 retrospective) of overall moderate quality that enrolled 1730 PAH patients were included. Oral anticoagulation (warfarin) was associated with a 31% mortality risk reduction (HR, 0.69; 95% confidence interval, 0.57-0.82; I(2) = 28%). Subgroup and sensitivity analyses showed similar results and no significant heterogeneity.
  
  
  CONCLUSIONS
  There is no randomized evidence to support the use of oral anticoagulation in PAH. Pooled results from cohort studies suggest a survival benefit, but the moderate study quality, the high risk of publication bias, and the methodological limitations inherent in the analysis of observational studies preclude a definite conclusion. There is an urgent need for pragmatic randomized evidence to definitely answer this important clinical question.
authors.affiliation: Clinical Pharmacology Unit, Instituto de Medicina Molecular, Lisbon, Portugal; Laboratory of Clinical Pharmacology and Therapeutics, Faculty of Medicine, University of Lisbon, Portugal; Cardiology Department, Hospital Garcia de Orta, Almada, Portugal. Electronic address: dgcaldeira@hotmail.com.
authors.forename: Daniel
authors.initials: D
authors.lastname: Caldeira
authors.affiliation: Cardiology Department, Hospital Garcia de Orta, Almada, Portugal.
authors.forename: Maria José
authors.initials: MJ
authors.lastname: Loureiro
authors.affiliation: Clinical Pharmacology Unit, Instituto de Medicina Molecular, Lisbon, Portugal; Laboratory of Clinical Pharmacology and Therapeutics, Faculty of Medicine, University of Lisbon, Portugal; Evidence Based Medicine Centre, Faculty of Medicine, University of Lisbon, Portugal; Portuguese Collaborating Centre of the Cochrane Iberoamerican Network, Faculty of Medicine, University of Lisbon, Portugal.
authors.forename: João
authors.initials: J
authors.lastname: Costa
authors.affiliation: Cardiology Department, CCUL, CAML, University of Lisbon, Portugal.
authors.forename: Fausto J
authors.initials: FJ
authors.lastname: Pinto
authors.affiliation: Clinical Pharmacology Unit, Instituto de Medicina Molecular, Lisbon, Portugal; Laboratory of Clinical Pharmacology and Therapeutics, Faculty of Medicine, University of Lisbon, Portugal.
authors.forename: Joaquim J
authors.initials: JJ
authors.lastname: Ferreira
mesh_terms: D000284:Administration, Oral; D000925:Anticoagulants / Q000627:therapeutic use*; D065627:Familial Primary Pulmonary Hypertension; D006801:Humans; D006976:Hypertension, Pulmonary / Q000097:blood / Q000188:drug therapy* / Q000401:mortality; D011379:Prognosis; D013923:Thromboembolism / Q000517:prevention & control*
chemical_list: D000925:Anticoagulants