Universität zu Köln

Noordegraaf, Anton Vonk, 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 and Galie, Nazzareno (2022). The REPAIR Study Effects of Macitentan on RV Structure and Function in Pulmonary Arterial Hypertension. JACC-Cardiovasc. Imag., 15 (2). S. 240 - 254. NEW YORK: ELSEVIER SCIENCE INC. ISSN 1876-7591

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Abstract

OBJECTIVES 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). BACKGROUND 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. METHODS 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. RESULTS 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. CONCLUSIONS 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) (J Am Coll Cardiol Img 2022;15:240-253) (C) 2022 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Noordegraaf, Anton Vonk UNSPECIFIED UNSPECIFIED UNSPECIFIED Channick, Richard UNSPECIFIED UNSPECIFIED UNSPECIFIED Cottreel, Emmanuelle UNSPECIFIED UNSPECIFIED UNSPECIFIED Kiely, David G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Marcus, J. Tim UNSPECIFIED UNSPECIFIED UNSPECIFIED Martin, Nicolas UNSPECIFIED UNSPECIFIED UNSPECIFIED Moiseeva, Olga UNSPECIFIED UNSPECIFIED UNSPECIFIED Peacock, Andrew UNSPECIFIED UNSPECIFIED UNSPECIFIED Swift, Andrew J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Tawakol, Ahmed UNSPECIFIED UNSPECIFIED UNSPECIFIED Torbicki, Adam UNSPECIFIED UNSPECIFIED UNSPECIFIED Rosenkranz, Stephan UNSPECIFIED UNSPECIFIED UNSPECIFIED Galie, Nazzareno UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-694272
DOI:	10.1016/j.jcmg.2021.07.027
Journal or Publication Title:	JACC-Cardiovasc. Imag.
Volume:	15
Number:	2
Page Range:	S. 240 - 254
Date:	2022
Publisher:	ELSEVIER SCIENCE INC
Place of Publication:	NEW YORK
ISSN:	1876-7591
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ENDOTHELIN-RECEPTOR ANTAGONIST; RIGHT-VENTRICULAR FUNCTION; COMBINATION THERAPY; PROGNOSTIC VALUE; SILDENAFIL; BOSENTAN; VOLUME Multiple languages Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/69427