title: Ambrisentan response in connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH) - A subgroup analysis of the ARIES-E clinical trial.
abstract: Pulmonary arterial hypertension (PAH) is a condition which may lead to right ventricular failure and early mortality and is an important complication in patients with connective tissue disease (CTD). Previously, the endothelin A selective receptor antagonist, ambrisentan, demonstrated efficacy and safety in treating patients with PAH due to WHO Group I etiologies. These analyses describe the 3-year efficacy and safety of ambrisentan in patients specifically with CTD associated PAH (CTD-PAH).
  
  
  
  Patients with CTD-PAH participating in the ARIES-1 and -2 clinical trials and their long-term extension were evaluated. Efficacy evaluations including 6-min walk distance (6MWD), clinical worsening, and survival were collected at routine study visits. Additional analyses of 6MWD categorical (30 m) breakpoints were conducted to determine any relationship between 6MWD and a prognostic threshold for survival.
  
  
  
  124 patients with CTD-PAH were evaluated. 62.6%, 57.3%, and 58.2% of CTD-PAH patients treated with ambrisentan exhibited increases in 6MWD at 1-, 2-, and 3- years respectively. At 3 years, 64% of patients were free from clinical worsening and 76% of patients were still alive (Kaplan-Meier estimates). Identified factors holding prognostic relevance for survival include: baseline functional class, CTD-PAH subgroup, patient sex, improvement in 6MWD ≥30 m over the first 12 weeks of treatment, the most recent 6MWD, and a 6MWD absolute threshold of 222 m.
  
  
  
  These first analyses of the 3-year treatment of CTD-PAH patients with ambrisentan revealed fewer clinical worsening events and improved survival compared to historical controls. Key exercise parameters were also identified which appear important in guiding treatment.
authors: Center for Lungs and Breathing, Department of Medicine, University of Colorado School of Medicine, Aurora, CO, USA.
authors: Aryeh
authors: A
authors: Fischer
authors: Royal Free Hospital and UCL Division of Medicine, London, UK.
authors: Christopher P
authors: CP
authors: Denton
authors: Department of Experimental and Clinical Medicine, Division of Rheumatology AOUC, University of Florence, Florence, Italy.
authors: Marco
authors: M
authors: Matucci-Cerinic
authors: Gilead Sciences, Inc., Foster City, CA, USA.
authors: Hunter
authors: H
authors: Gillies
authors: Gilead Sciences, Inc., Foster City, CA, USA.
authors: Christiana
authors: C
authors: Blair
authors: Gilead Sciences, Inc., Foster City, CA, USA.
authors: James
authors: J
authors: Tislow
authors: Inova Advanced Lung Disease Program, Department of Medicine, Inova Fairfax Hospital, Falls Church, VA, USA. Electronic address: steven.nathan@inova.org.
authors: Steven D
authors: SD
authors: Nathan
mesh_terms: D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D003240:Connective Tissue Diseases / Q000150:complications / Q000188:drug therapy* / Q000453:epidemiology; D004311:Double-Blind Method; D065130:Endothelin A Receptor Antagonists / Q000494:pharmacology*; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000150:complications / Q000188:drug therapy* / Q000453:epidemiology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D010666:Phenylpropionates / Q000008:administration & dosage / Q000494:pharmacology*; D011237:Predictive Value of Tests; D015995:Prevalence; D011724:Pyridazines / Q000008:administration & dosage / Q000494:pharmacology*; D016019:Survival Analysis; D016896:Treatment Outcome; D000070857:Walk Test / Q000379:methods
chemical_list: D000959:Antihypertensive Agents; D065130:Endothelin A Receptor Antagonists; D010666:Phenylpropionates; D011724:Pyridazines; C467894:ambrisentan
keywords: Ambrisentan; Connective tissue diseases; Outcome assessment; Pulmonary hypertension