Frantz Robert P, Desai Shashank S, Ewald Gregory, Franco Veronica, Hage Antoine, Horn Evelyn M, LaRue Shane J, Mathier Michael A, Mandras Stacy, Park Myung H, Ravichandran Ashwin K, Schilling Joel D, Wang I-Wen, Zolty Ronald, Rendon Gabriela Gomez, Rocco Mark A, Selej Mona, Zhao Carol, Rame J Eduardo
Department of Cardiovascular Medicine Mayo Clinic Rochester Minnesota United States of America.
Inova Fairfax Medical Center Falls Church Virginia United States of America.
Pulm Circ. 2024 Dec 4;14(4):e12446. doi: 10.1002/pul2.12446. eCollection 2024 Oct.
Macitentan is a dual endothelin receptor antagonist (ERA) approved for treating pulmonary arterial hypertension (PAH). SOPRANO evaluated the efficacy and safety of macitentan versus placebo in pulmonary hypertension (PH) patients after left ventricular assist device (LVAD) implantation. SOPRANO was a phase 2, multicenter, double-blind, randomized, placebo-controlled, parallel-group study. Patients with an LVAD implanted within the prior 90 days who had persistent PH (i.e., mean pulmonary arterial pressure ≥25 mmHg, pulmonary artery wedge pressure [PAWP] ≤18 mmHg, and pulmonary vascular resistance [PVR] >3 Wood units [WU]) were randomized (1:1) to macitentan 10 mg or placebo once daily for 12 weeks. The primary endpoint was change in PVR. Secondary endpoints included change in right-heart catheterization hemodynamic variables, N-terminal prohormone of brain natriuretic peptide levels, World Health Organization functional class, and safety/tolerability. Fifty-seven patients were randomized to macitentan ( = 28) or placebo ( = 29). A statistically significant reduction in PVR from baseline to Week 12 was observed with macitentan versus placebo (placebo-corrected geometric mean ratio, 0.74; 95% confidence interval, 0.58-0.94; = .0158). No statistically significant differences were observed in secondary endpoints. In a post-hoc analysis, 66.7% of patients receiving macitentan achieved PVR <3 WU versus 40.0% receiving placebo ( = .0383). Macitentan was generally well tolerated; adverse events were consistent with those in previous PAH studies with macitentan. In conclusion, macitentan showed promising tolerability and significantly reduced PVR in PH patients with persistently elevated PVR after LVAD implantation. ClinicalTrials. gov identifier: NCT02554903.
马昔腾坦是一种双重内皮素受体拮抗剂（ERA），已被批准用于治疗肺动脉高压（PAH）。SOPRANO评估了马昔腾坦与安慰剂对左心室辅助装置（LVAD）植入术后肺动脉高压（PH）患者的疗效和安全性。SOPRANO是一项2期、多中心、双盲、随机、安慰剂对照、平行组研究。在过去90天内植入LVAD且患有持续性PH（即平均肺动脉压≥25 mmHg、肺动脉楔压[PAWP]≤18 mmHg、肺血管阻力[PVR]>3伍德单位[WU]）的患者被随机（1:1）分为马昔腾坦10 mg组或安慰剂组，每日一次，共12周。主要终点是PVR的变化。次要终点包括右心导管血流动力学变量的变化、脑钠肽前体N端水平、世界卫生组织功能分级以及安全性/耐受性。57名患者被随机分为马昔腾坦组（n = 28）或安慰剂组（n = 29）。与安慰剂相比，马昔腾坦治疗从基线到第12周时PVR有统计学显著降低（安慰剂校正几何平均比值，0.74；95%置信区间，0.58 - 0.94；P = 0.0158）。次要终点未观察到统计学显著差异。在一项事后分析中，接受马昔腾坦治疗的患者中有66.7%的PVR<3 WU，而接受安慰剂治疗的患者为40.0%（P = 0.0383）。马昔腾坦总体耐受性良好；不良事件与既往马昔腾坦治疗PAH的研究一致。总之，马昔腾坦在LVAD植入后PVR持续升高的PH患者中显示出良好的耐受性，并显著降低了PVR。ClinicalTrials.gov标识符：NCT02554903。
