Upfront riociguat and ambrisentan combination therapy for newly diagnosed pulmonary arterial hypertension: A prospective open-label trial

J Heart Lung Transplant. 2022 May;41(5):563-567. doi: 10.1016/j.healun.2022.01.002. Epub 2022 Jan 10.


Background: Initial combination therapy with an endothelin receptor antagonist (ERA) and riociguat in pulmonary arterial hypertension (PAH) has limited supporting data.

Methods: We performed a prospective, single-arm, open-label trial of riociguat, and ambrisentan for incident PAH patients in functional class III. The primary endpoint was pulmonary vascular resistance (PVR) at 4-months.

Results: Twenty patients (59 ± 13 years old, 85% female) enrolled and 1 died before their 4-month follow-up. Fifteen patients completed a 4-month and 13 completed the 12-month follow-up. At 4-months PVR decreased 54% with an absolute change of -5.8 Wood units (95% CI -4.0; -7.5, p < 0.001). Other hemodynamic variables and risk scores also improved. Six patients discontinued riociguat and 8 discontinued ambrisentan, with 5 (25%) discontinuing both.

Conclusions: These results do not support the routine use of riociguat plus ambrisentan in initial regimens. Future studies are needed to compare this strategy with phosphodiesterase-5 inhibitors and an ERA with respect to tolerability and long-term outcomes.

Keywords: ambrisentan; combination therapy; pulmonary arterial hypertension; riociguat.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antihypertensive Agents / therapeutic use
  • Endothelin Receptor Antagonists / therapeutic use
  • Familial Primary Pulmonary Hypertension / drug therapy
  • Female
  • Humans
  • Hypertension, Pulmonary* / diagnosis
  • Hypertension, Pulmonary* / drug therapy
  • Male
  • Middle Aged
  • Phenylpropionates
  • Prospective Studies
  • Pulmonary Arterial Hypertension*
  • Pyrazoles
  • Pyridazines
  • Pyrimidines
  • Treatment Outcome


  • Antihypertensive Agents
  • Endothelin Receptor Antagonists
  • Phenylpropionates
  • Pyrazoles
  • Pyridazines
  • Pyrimidines
  • ambrisentan
  • riociguat