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

Ioana R. Preston, Charles D. Burger, Sonja Bartolome, Zeenat Safdar, Michael Krowka, Namita Sood, Hubert J. Ford, Wejdan F. Battarjee, Murali M. Chakinala, Mardi Gomberg-Maitland, Nicholas S. Hill

Research output: Contribution to journalArticlepeer-review

27 Scopus citations


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/m 2, 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).

Original languageEnglish (US)
Pages (from-to)464-472
Number of pages9
JournalJournal of Heart and Lung Transplantation
Issue number5
StatePublished - May 2020


  • ambrisentan
  • clinical trial
  • endothelin receptor antagonists
  • portopulmonary hypertension
  • pulmonary arterial hypertension
  • treatment
  • Antihypertensive Agents/therapeutic use
  • Echocardiography
  • Prospective Studies
  • Follow-Up Studies
  • Humans
  • Middle Aged
  • Phenylpropionates/therapeutic use
  • Male
  • Pulmonary Wedge Pressure/drug effects
  • Treatment Outcome
  • Hypertension, Pulmonary/diagnosis
  • Vascular Resistance/drug effects
  • Female
  • Pyridazines/therapeutic use

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Transplantation
  • Pulmonary and Respiratory Medicine
  • Surgery


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