Hemodynamics and risk assessment 2 years after the initiation of upfront ambrisentan‒tadalafil in pulmonary arterial hypertension

J Heart Lung Transplant. 2020 Dec;39(12):1389-1397. doi: 10.1016/j.healun.2020.08.016. Epub 2020 Aug 28.


Background: Upfront combination therapy with ambrisentan and tadalafil has been reported to improve the condition of patients with pulmonary arterial hypertension (PAH) more than with either drug alone. However, little is known about the long-term associated changes in hemodynamics and risk assessment scores.

Methods: This was a multicenter, retrospective analysis of clinical data in 106 patients with newly diagnosed PAH. Clinical evaluations, including demographics, medical history, World Health Organization (WHO) functional class (FC) and 6-minute walk distance (6MWD), right heart catheterization, and Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) risk score 2.0, were assessed over 48 months of ambrisentan‒tadalafil therapy.

Results: At baseline, 9 patients (9%) showed a low (<7), 48 patients (45%) showed an intermediate (7-8), and 49 patients (46%) showed a high (>8) REVEAL risk score. At a median follow-up of 2 years, 45 patients (43%) showed a low, 47 patients (44%) showed an intermediate, and 14 patients (13%) showed a high REVEAL score, along with improvements in WHO FC, 6MWD and a decrease in mean pulmonary artery pressure and N-terminal pro brain natriuretic peptide (all p < 0.001). Pulmonary vascular resistance (PVR) decreased by 37% from 11.5 ± 6.5 to 7.2 ± 4.1 Wood units (p < 0.001). A total of 61 patients (57%) remained in intermediate-risk or high-risk categories. Low-risk patients had either a decrease in PVR of >50% or a stroke volume within the limits of normal.

Conclusions: Initial combination therapy with ambrisentan and tadalafil in PAH improves the REVEAL risk score in proportion to decreased PVR and preserved stroke volume but still insufficiently so in approximately 50% of the patients.

Keywords: European risk score; REVEAL risk score; combination therapy; prognosis; pulmonary arterial hypertension; risk assessment.

Publication types

  • Multicenter Study

MeSH terms

  • Antihypertensive Agents / therapeutic use
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Hemodynamics / drug effects
  • Hemodynamics / physiology*
  • Humans
  • Male
  • Middle Aged
  • Phenylpropionates / therapeutic use*
  • Pulmonary Arterial Hypertension / drug therapy
  • Pulmonary Arterial Hypertension / physiopathology*
  • Pyridazines / therapeutic use*
  • Retrospective Studies
  • Risk Assessment / methods*
  • Tadalafil / therapeutic use*
  • Time Factors
  • Treatment Outcome
  • Vasodilator Agents / therapeutic use


  • Antihypertensive Agents
  • Phenylpropionates
  • Pyridazines
  • Vasodilator Agents
  • Tadalafil
  • ambrisentan