Long-Term Outcomes With Ambrisentan Monotherapy in Pulmonary Arterial Hypertension
Received 3 June 2009; received in revised form 30 August 2009; accepted 29 September 2009. published online 23 November 2009.
Abstract
Background
This study evaluated long-term outcomes in patients with pulmonary arterial hypertension (PAH) undergoing treatment with ambrisentan monotherapy, a selective oral endothelin-1 receptor antagonist.
Methods and Results
Patients who participated in the Ambrisentan in Pulmonary Arterial Hypertension: A Phase 3, Randomized, Double-Blind, Placebo-Controlled Multicenter Efficacy Study (ARIES-1) clinical trial and extension phase at our institution were included. Cardiac catheterization, 6-minute walk distance (6MWD), and cardiac magnetic resonance (MRI) data were retrospectively reviewed. Twelve patients with PAH (11 idiopathic, 1 fenfluramine) had follow-up from 3 to 5.5 years from the initiation of ARIES-1. Patients received ambrisentan therapy throughout the study period and were on ambrisentan monotherapy for the first 2 years. At year 1, improvements in median mean pulmonary arterial pressure (PA), cardiac output, and pulmonary vascular resistance (PVR) were seen (P = .02, P = .03, P < .01), and the improvement in PVR persisted at 2 years. 6MWD also improved significantly between baseline (350 m) and 1 and 2 years (397 m, P < .01 and 393 m, P = .01). Cardiac MRI results were more varied, with an increase in RV ejection fraction from 29% at baseline to 46% at 2 years (P = .02), but other MRI variables did not improve.
Conclusions
Ambrisentan monotherapy led to improvements in catheterization, 6MWD, and RV ejection fraction, and shows promise as a long-term treatment for pulmonary arterial hypertension.
2Parkland Hospital/UT Southwestern University Hospital, University of Texas Southwestern Medical Center at Dallas
Reprint requests: Shannon Blalock, 1935 Medical Center Drive, Division of Cardiology, 3rd Floor, Dallas, TX 75235. Phone: (214) 456-6333; Fax: (214) 456-6154.
Supported by Grant Number UL1RR024982 and KL2RR024983, titled, “North and Central Texas Clinical and Translational Science Initiative” (Milton Packer, MD, PI) from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH) and NIH Roadmap for Medical Research, and its contents are solely the responsibility of the authors and do not necessarily represent the official view of the NCRR or NIH. Information on NCRR is available at http://www.ncrr.nih.gov/. Information on Re-engineering the Clinical Research Enterprise can be obtained from http://nihroadmap.nih.gov/clinicalresearch/overview-translational.asp.
Dr. Torres has served as a speaker/consultant and has received research grants from Gilead, which makes ambrisentan. Dr. Chin has received research grants from Gilead and has served as a speaker/consultant for Actelion and United Therapeutics.
ABSTRACT