Ambrisentan in portopulmonary hypertension: A multicenter, open-label trial

J Heart Lung Transplant. 2020 May;39(5):464-472. doi: 10.1016/j.healun.2019.12.008. Epub 2020 Jan 21.

Abstract

Background: Ambrisentan has shown effectiveness in the treatment of Group 1 pulmonary arterial hypertension (PAH). Although portopulmonary hypertension (PoPH) is a subset of Group 1 PAH, few clinical trials have been testing PAH therapies in patients with PoPH. The objective of this study is to evaluate the efficacy and safety of ambrisentan in PoPH.

Methods: This study is a prospective, multicenter, open-label trial in which treatment-naive patients with PoPH with Child-Pugh class A/B were administered with ambrisentan for 24 weeks, followed by a long-term extension (24-28 weeks). The primary end-points were change in pulmonary vascular resistance (PVR) and 6-minutes walk distance (6MWD) at 24 weeks, whereas secondary end-points included safety, World Health Organization (WHO) functional class (FC) and echocardiographic assessments.

Results: Of the 31 patients, 23 finished 24 weeks of ambrisentan therapy and 19 finished the extension. PVR decreased significantly (mean ± SD) (7.1 ± 5 vs 3.8 ± 1.8 Wood units, p < 0.001), whereas 6MWD remained unchanged (314 ± 94 vs 336 ± 108 m). Other hemodynamic parameters such as right atrial pressure (13 ± 8 vs 9 ± 4 mm Hg, p < 0.05), mean pulmonary arterial pressure (46 ± 13 vs. 38 ± 8 mm Hg, p < 0.01), cardiac index (2.6 ± 0.6 vs. 3.5 ± 0.7 liter/min/m2, p < 0.001) showed improvement, whereas pulmonary capillary wedge pressure remained unchanged. Of the 22 patients with WHO FC assessments at baseline and 24 weeks, WHO FC improved significantly (p = 0.005). Most frequent drug-related adverse events were edema (38.7%) and headache (22.5%). One episode of leg edema resulted into the permanent discontinuation of ambrisentan.

Conclusions: Ambrisentan monotherapy in PoPH improves hemodynamics and FC at 24 weeks; however, it did not show any improvement in 6MWD. These preliminary outcomes should be interpreted with caution (Clinicaltrials.Gov:NCT01224210).

Keywords: ambrisentan; clinical trial; endothelin receptor antagonists; portopulmonary hypertension; pulmonary arterial hypertension; treatment.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antihypertensive Agents / therapeutic use
  • Echocardiography
  • Female
  • Follow-Up Studies
  • Humans
  • Hypertension, Pulmonary / diagnosis
  • Hypertension, Pulmonary / drug therapy*
  • Hypertension, Pulmonary / physiopathology
  • Male
  • Middle Aged
  • Phenylpropionates / therapeutic use*
  • Prospective Studies
  • Pulmonary Wedge Pressure / drug effects
  • Pyridazines / therapeutic use*
  • Treatment Outcome
  • Vascular Resistance / drug effects*

Substances

  • Antihypertensive Agents
  • Phenylpropionates
  • Pyridazines
  • ambrisentan

Associated data

  • ClinicalTrials.gov/NCT01224210