First Results of Soprano: Macitentan in Patients (pts) with Pulmonary Hypertension (PH) Post-Left Ventricular Assist Device (LVAD) Implantation

Purpose To assess the efficacy and safety of macitentan in pts with PH post-LVAD. Methods SOPRANO (NCT02554903) was a double-blind, randomized, study of macitentan 10 mg once-daily vs placebo. Pts were ≥18 years with LVAD implanted within 90 days prior to randomization, had mean pulmonary arterial pressure (mPAP) ≥25 mmHg, pulmonary artery wedge pressure (PAWP) ≤18 mmHg and pulmonary vascular resistance (PVR) >3 Wood units (WU). The primary endpoint was change in PVR at week 12 of therapy from baseline. Results Fifty-seven pts were randomized: macitentan (n=28) or placebo (n=29). Baseline pt demographics and characteristics were well balanced. Baseline PVR (mean [SD]) was 4.3 [0.9] WU (macitentan) and 4.3 [1.3] WU (placebo). At week 12, mean PVR decreased to 58.5% (macitentan) and to 75.5% (placebo) of baseline. Mean placebo-corrected reduction in PVR of macitentan was 26.1% (95% CI: 58.0, 94.3; p=0.0158). Predefined secondary endpoints, notably including changes in PAWP, were not significantly different with macitentan vs placebo (Table). Another relevant hemodynamic parameter, transpulmonary gradient, significantly decreased with macitentan vs placebo (p=0.0499). The incidence of treatment adverse events (TAEs) was 21.4% (macitentan) and 24.1% (placebo); no TAEs occurred in >1 patient in the macitentan arm. AEs of interest included edema, anemia and hypotension: reported in 7 (25.0%), 3 (10.7%), and 4 (14.3%) pts on macitentan (mostly mild-moderate) and in 5 (17.2%), 2 (6.9%) and 1 (3.6%) pts on placebo, respectively. Two pts on macitentan and 1 pt on placebo discontinued for treatment-related AEs. Conclusion In the first prospective, multicenter, randomized controlled trial of pulmonary vasodilators in the early post-LVAD population, macitentan significantly reduced PVR and was well tolerated. The impact of macitentan on post-LVAD exercise capacity and RV failure warrants further study.