title: Rationale and design of a phase II clinical trial of aspirin and simvastatin for the treatment of pulmonary arterial hypertension: ASA-STAT.
abstract: BACKGROUND
  Pulmonary arterial hypertension (PAH) is a progressive disease which causes exercise limitation, heart failure, and death. Aspirin and simvastatin are highly effective and safe therapies for other cardiovascular diseases characterized by platelet activation and endothelial dysfunction, but have not been formally studied in PAH.
  
  
  METHODS
  ASA-STAT is a phase II, randomized, double-blind, placebo-controlled 2 × 2 factorial clinical trial of aspirin and simvastatin in patients with PAH. A total of 92 subjects were to be randomized to aspirin or aspirin placebo and simvastatin or simvastatin placebo. The primary outcome is the distance walked in 6 min at 6 months after randomization. Secondary measures include brachial artery flow-mediated dilation, circulating biomarkers of platelet and endothelial function, functional class, quality-of-life, and time to clinical end points. The incidence of adverse events will be compared between treatment groups. SCREENING AND ENROLLMENT: We screened a total of 712 individuals with PAH. Sixty-five subjects were enrolled when the trial was terminated for futility in reaching the primary end point for simvastatin.
  
  
  CONCLUSIONS
  This study aims to determine whether aspirin or simvastatin have beneficial biologic or clinical effects in patients with PAH. The safety and side effects of these commonly prescribed cardiovascular drugs will also be assessed.
authors.affiliation: Penn Cardiovascular Institute, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, United States. kawut@upenn.edu
authors.forename: Steven M
authors.initials: SM
authors.lastname: Kawut
authors.forename: Emilia
authors.initials: E
authors.lastname: Bagiella
authors.forename: Daichi
authors.initials: D
authors.lastname: Shimbo
authors.forename: David J
authors.initials: DJ
authors.lastname: Lederer
authors.forename: Nadine
authors.initials: N
authors.lastname: Al-Naamani
authors.forename: Kari E
authors.initials: KE
authors.lastname: Roberts
authors.forename: R Graham
authors.initials: RG
authors.lastname: Barr
authors.forename: Wendy
authors.initials: W
authors.lastname: Post
authors.forename: Evelyn M
authors.initials: EM
authors.lastname: Horn
authors.forename: Russell
authors.initials: R
authors.lastname: Tracy
authors.forename: Paul
authors.initials: P
authors.lastname: Hassoun
authors.forename: Reda
authors.initials: R
authors.lastname: Girgis
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000627:therapeutic use*; D001241:Aspirin / Q000008:administration & dosage / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D003627:Data Interpretation, Statistical; D004311:Double-Blind Method; D065627:Familial Primary Pulmonary Hypertension; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D006976:Hypertension, Pulmonary / Q000188:drug therapy; D019007:P-Selectin / Q000097:blood; D011788:Quality of Life; D016032:Randomized Controlled Trials as Topic / Q000379:methods; D019821:Simvastatin / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D015415:Biomarkers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019007:P-Selectin; D002097:C-Reactive Protein; D019821:Simvastatin; D001241:Aspirin