title: Long-term pulmonary hemodynamic effects of ambrisentan in pulmonary arterial hypertension.
abstract: The long-term effects of endothelin receptor antagonists on pulmonary arterial pressure (PAP) and pulmonary vascular resistance (PVR) in patients with pulmonary arterial hypertension (PAH) are not well studied. This post hoc analysis examined changes in pulmonary hemodynamics in a cohort of patients with PAH who underwent follow-up right heart catheterization (RHC) in a long-term ambrisentan study (ARIES-E). A retrospective review was conducted of patients who underwent RHC after >3 months of ambrisentan therapy. Changes from baseline in mean PAP, mean right atrial pressure, cardiac index, and PVR were assessed and correlations between these hemodynamic changes and exercise capacity were examined. Sixty-eight patients who received ambrisentan in the ARIES studies had ≥1 follow-up RHC while receiving ambrisentan. Fifty-eight patients were on ambrisentan alone at the time of the first RHC. Median time from initiation of ambrisentan therapy to follow-up RHC was 60 weeks (range 14 to 158). Significant improvements compared to baseline were observed for mean PAP (-7.6 mm Hg, 95% confidence interval [CI] -10.0 to -5.1), PVR (-266 dyne × s/cm(5), 95% CI -350 to -180), and cardiac index (0.4 L/min/m(2), 95% CI 0.2 to 0.6 L/min/m(2)); for patients on ambrisentan alone, changes in mean PAP and PVR were inversely correlated with change from baseline 6-minute walking distance (r = -0.41 and -0.43, respectively, p <0.001 for the 2 comparisons) at time of follow-up RHC. In conclusion, ambrisentan may provide sustained improvements in pulmonary hemodynamics in patients with PAH who receive long-term treatment and these changes correlate with improvements in exercise capacity.
authors.affiliation: Division of Pulmonary, Sleep and Critical Care Medicine, Rhode Island Hospital, USA. James_Klinger@brown.edu
authors.forename: James R
authors.initials: JR
authors.lastname: Klinger
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Oudiz
authors.forename: Rebecca
authors.initials: R
authors.lastname: Spence
authors.forename: Darrin
authors.initials: D
authors.lastname: Despain
authors.forename: Christopher
authors.initials: C
authors.lastname: Dufton
mesh_terms: D000959:Antihypertensive Agents / Q000627:therapeutic use*; D016280:Atrial Function, Right / Q000187:drug effects; D006328:Cardiac Catheterization; D002302:Cardiac Output / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005080:Exercise Test; D017079:Exercise Tolerance / Q000187:drug effects; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D010666:Phenylpropionates / Q000627:therapeutic use*; D011669:Pulmonary Wedge Pressure / Q000187:drug effects; D011724:Pyridazines / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D014655:Vascular Resistance
chemical_list: D000959:Antihypertensive Agents; D010666:Phenylpropionates; D011724:Pyridazines; C467894:ambrisentan