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/m(2) vs. - 0.31 +/- 0.71 l/min/m(2), 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/m(2) vs. - 0.45 +/- 1.36 l/min/m(2), 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 14(th) of November 2014.
- Pan, Z.
- Marra, A. M.
- Benjamin, N.
- Eichstaedt, C. A.
- Blank, N.
- Bossone, E.
- Cittadini, A.
- Coghlan, G.
- Denton, C. P.
- Distler, O.
- Egenlauf, B.
- Fischer, C.
- Harutyunova, S.
- Xanthouli, P.
- Lorenz, H. M.
- Grunig, E.
Keywords
- *Ambrisentan
- *Borderline pulmonary hypertension
- *Exercise PH
- *Mildly elevated mPAP
- *Placebo-controlled
- *Treatment