Upfront combination therapy in the treatment of scleroderma-associated pulmonary arterial hypertension: Results of an open label trial

Introduction: Scleroderma-associated pulmonary arterial hypertension (SSc-PAH) responds poorly to current PAH therapy. Aims: To assess the effects of upfront, combination therapy with tadalafil and ambrisentan in a multicenter, prospective open label trial for treatment of SSc-PAH. Methods: 25 treatment naive SSc-PAH patients received tadalafil (40 mg daily) and ambrisentan (10 mg daily) for 36 weeks. Right heart catheterization, cMRI, and echocardiography were performed at baseline and 36 weeks. Primary endpoints were changes in RV mass and PVR. Secondary endpoints were changes in pulmonary compliance (Pca=stroke volume over pulmonary pulse pressure), ventricular mass index (VMI=RV/LV mass index), tricuspid annular plane systolic excursion (TAPSE), six-minute walk distance (6 MWD) and N-terminal pro-brain natriuretic peptide (NTproBNP). Results: Treatment resulted in significant reductions in RV mass index (21.7±10.6 g/m² vs 18.0±6.7 g/m²; P =0.04), PVR (8.1±5.8 Wood Units (WU) vs. 3.9±3.5 WU; P Conclusions: Upfront combination therapy resulted in significant changes in hemodynamics, RV structure and function, and RV-pulmonary vascular coupling as well as functional status at 36 weeks of therapy. When compared to previous clinical trials, these data suggest initial combination therapy is very effective for SSc-PAH.