C66-15 Cardiac Magnetic Resonance Imaging (CMR) Sub-study of UNISUS In Pulmonary Arterial Hypertension (PAH): Characteristics of Enrolled Patients

Rationale Macitentan is a dual endothelin receptor antagonist targeting endothelin (ET) A and ETB receptors. At the approved dose in PAH of 10 mg once-daily (o.d.), macitentan primarily inhibits ETA receptors, and has demonstrated positive effects on right ventricular (RV) structure and function. UNISUS, the first head-to-head superiority trial in PAH, compares efficacy and safety of macitentan 75 mg versus 10 mg, evaluating the potential added benefit of maximally targeting both ETA and ETB receptors with macitentan 75 mg. A dedicated UNISUS CMR sub-study will assess RV and pulmonary artery (PA) properties and provide insights into the functional and structural changes associated with the potential superior efficacy of macitentan 75 mg versus 10 mg. The UNISUS study design and preliminary baseline characteristics of patients enrolled in the CMR sub-study are reported. Methods UNISUS (NCT04273945) is an ongoing phase 3, prospective, multicenter, double-blind, double-dummy, randomized, active-controlled, parallel-group, group-sequential, adaptive, event-driven superiority study in patients with PAH, randomized 1:1 to receive macitentan 75 mg or 10 mg o.d. Adult patients in WHO functional class (FC) II-IV, with or without prior PAH treatment, were eligible. Patients in the CMR sub-study underwent imaging at baseline, Week 24 and Week 52 to assess changes in cardiac structure/function and in PA stiffness. Images were centrally read and measurements included RV end-diastolic volume (RVEDV), RV end-systolic volume (RVESV), RV stroke volume (RVSV), RV ejection fraction (RVEF), RV mass (RVM), RVM: RVEDV, PA pulse wave velocity (PWV), and PA relative area change. Results The UNISUS CMR sub-study enrolled 90 patients at 20 sites (overall: 935 patients at 229 sites). At baseline, mean age was 44.8 years, 78.9% were female and median time since diagnosis was 4.7 years (Table). Most patients had idiopathic PAH (38.9%) or PAH associated with connective tissue disease (21.1%) or congenital heart disease (21.1%). Most were in WHO FC II (71.1%). At screening, 46.7% were receiving 1 PAH therapy and 52.2% ≥2 PAH therapies. Mean values for CMR parameters at baseline were RVEDV: 202.1 mL, RVESV: 130.0 mL, RVSV: 69.0 mL, RVEF: 38.0%, RVM: 44.2 g, RVM: RVEDV: 0.22, PWV: 3.0 m/s, and PA relative area change: 0.24. Conclusions The UNISUS CMR sub-study will assess the impact of macitentan 75 mg versus macitentan 10 mg on RV and PA structure and function. Findings from the study may provide mechanistic insights into how maximal ETA and ETB blockade benefits patients with PAH.