Vonk Noordegraaf Anton, Channick Richard, Cottreel Emmanuelle, Kiely David G, Marcus J Tim, Martin Nicolas, Moiseeva Olga, Peacock Andrew, Swift Andrew J, Tawakol Ahmed, Torbicki Adam, Rosenkranz Stephan, Galiè Nazzareno
Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
JACC Cardiovasc Imaging. 2022 Feb;15(2):240-253. doi: 10.1016/j.jcmg.2021.07.027. Epub 2021 Nov 17.
The REPAIR (Right vEntricular remodeling in Pulmonary ArterIal hypeRtension) study evaluated the effect of macitentan on right ventricular (RV) and hemodynamic outcomes in patients with pulmonary arterial hypertension (PAH), using cardiac magnetic resonance (CMR) and right heart catheterization (RHC).
RV failure is the primary cause of death in PAH. CMR is regarded as the most accurate noninvasive method for assessing RV function and remodeling and CMR measures of RV function and structure are strongly prognostic for survival in patients with PAH. Despite this, CMR is not routinely used in PAH clinical trials.
REPAIR was a 52-week, open-label, single-arm, multicenter, phase 4 study evaluating the effect of macitentan 10 mg, with or without phosphodiesterase type-5 inhibition, on RV remodeling and function and cardiopulmonary hemodynamics. Primary endpoints were change from baseline to week 26 in RV stroke volume, determined by CMR; and pulmonary vascular resistance, determined by RHC. Efficacy measures were assessed for all patients with baseline and week 26 data for both primary endpoints.
At a prespecified interim analysis in 42 patients, both primary endpoints were met, enrollment was stopped, and the study was declared positive. At final analysis (n = 71), RV stroke volume increased by 12 mL (96% confidence level: 8.4-15.6 mL; P < 0.0001) and pulmonary vascular resistance decreased by 38% (99% confidence level: 31%-44%; P < 0.0001) at week 26. Significant positive changes were also observed in secondary and exploratory CMR (RV and left ventricular), hemodynamic, and functional endpoints at week 26. Improvements in CMR RV and left ventricular variables and functional parameters were maintained at week 52. Safety (n = 87) was consistent with previous clinical trials.
In the context of this study, macitentan treatment in patients with PAH resulted in significant and clinically-relevant improvements in RV function and structure and cardiopulmonary hemodynamics. At 52 weeks, improvements in RV function and structure were sustained. (REPAIR: Right vEntricular remodeling in Pulmonary ArterIal hypeRtension [REPAIR]; NCT02310672).
“修复”（肺动脉高压患者右心室重塑）研究使用心脏磁共振成像（CMR）和右心导管检查（RHC），评估马昔腾坦对肺动脉高压（PAH）患者右心室（RV）及血流动力学指标的影响。
右心室衰竭是PAH患者的主要死亡原因。CMR被认为是评估右心室功能和重塑最准确的非侵入性方法，右心室功能和结构的CMR测量对PAH患者的生存具有很强的预后价值。尽管如此，CMR在PAH临床试验中并未常规使用。
“修复”研究是一项为期52周、开放标签、单臂、多中心的4期研究，评估10毫克马昔腾坦（无论有无5型磷酸二酯酶抑制）对右心室重塑和功能以及心肺血流动力学的影响。主要终点为通过CMR测定的右心室每搏输出量从基线至第26周的变化；以及通过RHC测定的肺血管阻力。对所有具有两个主要终点的基线和第26周数据的患者进行疗效评估。
在对42例患者进行的预定中期分析中，两个主要终点均达到，入组停止，研究宣布为阳性。在最终分析（n = 71）中，第26周时右心室每搏输出量增加了12毫升（96%置信区间：8.4 - 15.6毫升；P < 0.0001），肺血管阻力降低了38%（99%置信区间：31% - 44%；P < 0.0001）。在第26周时，次要和探索性CMR（右心室和左心室）、血流动力学及功能终点也观察到显著的正向变化。右心室和左心室的CMR变量及功能参数在第52周时仍保持改善。安全性（n = 87）与既往临床试验一致。
在本研究背景下，PAH患者接受马昔腾坦治疗后，右心室功能和结构以及心肺血流动力学有显著且具有临床意义的改善。在52周时，右心室功能和结构的改善得以持续。（“修复”：肺动脉高压患者右心室重塑[REPAIR]；NCT02310672）
