title: Warfarin in systemic sclerosis-associated and idiopathic pulmonary arterial hypertension. A Bayesian approach to evaluating treatment for uncommon disease.
abstract: OBJECTIVE
  Warfarin is recommended in systemic sclerosis-associated pulmonary arterial hypertension (SSc-PAH) and idiopathic PAH (IPAH) to improve survival. There is no evidence to support this in SSc-PAH and the evidence in IPAH is conflicting. We evaluated the ability of warfarin to improve survival using 2 large SSc-PAH and IPAH cohorts.
  
  
  METHODS
  The effect of warfarin on all-cause mortality was evaluated. Bayesian propensity scores (PS) were used to adjust for baseline differences between patients exposed and not exposed to warfarin, and to assemble a matched cohort. Bayesian Cox proportional hazards models were constructed using informative priors based on international PAH expert elicitation.
  
  
  RESULTS
  Review of 1138 charts identified 275 patients with SSc-PAH (n = 78; 28% treated with warfarin) and 155 patients with IPAH (n = 91; 59% treated with warfarin). Baseline differences in PAH severity and medications were resolved using PS matching. In the matched cohort of 98 patients with SSc-PAH (49 treated with warfarin), the posterior median hazard ratio (HR) was 1.06 [95% credible interval (CrI) 0.70, 1.63]. In the matched cohort of 66 patients with IPAH (33 treated with warfarin), the posterior median HR was 1.07 (95% CrI 0.57, 1.98). The probability that warfarin improves median survival by 6 months or more is 23.5% in SSc-PAH and 27.7% in IPAH. Conversely, there is a > 70% probability that warfarin provides no significant benefit or is harmful.
  
  
  CONCLUSIONS
  There is a low probability that warfarin improves survival in SSc-PAH and IPAH. Given the availability of other PAH therapies with demonstrable benefits, there is little reason to use warfarin to improve survival for these patients.
authors.affiliation: Division of Rheumatology, Department of Medicine, Toronto Western Hospital, Toronto, Ontario, Canada. Sindhu.Johnson@uhn.on.ca
authors.forename: Sindhu R
authors.initials: SR
authors.lastname: Johnson
authors.forename: John T
authors.initials: JT
authors.lastname: Granton
authors.forename: George A
authors.initials: GA
authors.lastname: Tomlinson
authors.forename: Haddas A
authors.initials: HA
authors.lastname: Grosbein
authors.forename: Thaolan
authors.initials: T
authors.lastname: Le
authors.forename: Peter
authors.initials: P
authors.lastname: Lee
authors.forename: M Elizabeth
authors.initials: ME
authors.lastname: Seary
authors.forename: Gillian A
authors.initials: GA
authors.lastname: Hawker
authors.forename: Brian M
authors.initials: BM
authors.lastname: Feldman
mesh_terms: D000925:Anticoagulants / Q000627:therapeutic use*; D001499:Bayes Theorem; D002423:Cause of Death; D015331:Cohort Studies; D065627:Familial Primary Pulmonary Hypertension; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D016016:Proportional Hazards Models; D012595:Scleroderma, Systemic / Q000188:drug therapy* / Q000401:mortality; D016896:Treatment Outcome; D014859:Warfarin / Q000627:therapeutic use*
chemical_list: D000925:Anticoagulants; D014859:Warfarin