Objective: The objective of this randomized, placebo-controlled, double-blind, parallel group, trial was to assess the effect of ambrisentan on mean pulmonary arterial pressure (mPAP) in patients with systemic sclerosis (SSc) and mildly elevated pulmonary hypertension (PH). Methods: Thirty-eight SSc patients with mildly elevated mPAP at rest between 21 and 24 mmHg and/or > 30 mmHg during low-dose exercise were randomly assigned to treatment with either ambrisentan 5-10 mg/day or placebo. Right heart catheterization and further clinical parameters were assessed at baseline and after 6 months. The primary endpoint was the difference of mPAP change at rest between groups. Results: After 6 months, the two groups did not differ in the primary endpoint (ambrisentan mPAP-1 ± 6.4 mmHg vs. placebo-0.73 ± 3.59 mmHg at rest, p = 0.884). However, three patients from the placebo group but none of the ambrisentan group progressed to SSc-associated pulmonary arterial hypertension. Furthermore, ambrisentan treatment showed significant improvements in the secondary endpoints cardiac index (CI) and pulmonary vascular resistance (PVR) at rest (CI 0.36 ± 0.66 l/min/m2 vs.-0.31 ± 0.71 l/min/m2, p = 0.010; PVR-0.70 ± 0.78 WU vs. 0.01 ± 0.71 WU, p = 0.012) and during exercise (CI 0.7 ± 0.81 l/min/m2 vs.-0.45 ± 1.36 l/min/m2, p = 0.015; PVR-0.84 ± 0.48 WU vs.-0.0032 ± 0.34 WU, p < 0.0001). Conclusion: This is the first randomized, double-blind, placebo-controlled study testing the effect of ambrisentan in patients with mildly elevated mPAP and/or exercise PH. The primary endpoint change in mPAP did only tendentially improve in the ambrisentan group, but the significant improvement of other hemodynamic parameters points to a possible benefit of ambrisentan and will be helpful to design future trials. Trial registration: www.ClinicalTrials.gov, unique identifier NCT: NCT02290613, registered 14th of November 2014.
- Borderline pulmonary hypertension
- Exercise PH
- Mildly elevated mPAP
ASJC Scopus subject areas
- Immunology and Allergy