Anton Vonk Noordegraaf1, Richard Channick2, Emmanuelle Cottreel3, David G Kiely4, J Tim Marcus5, Nicolas Martin3, Olga Moiseeva6, Andrew Peacock7, Andrew J Swift8, Ahmed Tawakol9, Adam Torbicki10, Stephan Rosenkranz11, Nazzareno Galiè12. 1. Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands. Electronic address: a.vonk@amsterdamumc.nl. 2. David Geffen School of Medicine at UCLA, Los Angeles, California, USA. 3. Actelion Pharmaceuticals Ltd, Allschwil, Switzerland. 4. Sheffield Pulmonary Vascular Disease Unit, Royal Hallamshire Hospital, Sheffield, United Kingdom. 5. Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands. 6. Almazov National Medical Research Centre, St. Petersburg, Russia. 7. Scottish Pulmonary Vascular Unit, Glasgow, United Kingdom. 8. Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, United Kingdom. 9. Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA. 10. Department of Pulmonary Circulation, Thromboembolic Diseases and Cardiology, Centre of Postgraduate Medical Education, ECZ-Otwock, Otwock, Poland. 11. Department of Cardiology, Heart Center at the University of Cologne, and Cologne Cardiovascular Research Center (CCRC), Cologne, Germany. 12. Department of Experimental, Diagnostic and Specialty Medicine-DIMES, University of Bologna, Bologna, Italy.
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).
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).
Authors: Faisal Alandejani; Abdul Hameed; Euan Tubman; Samer Alabed; Yousef Shahin; Robert A Lewis; Krit Dwivedi; Aqeeb Mahmood; Jennifer Middleton; Lisa Watson; Dheyaa Alkhanfar; Christopher S Johns; Smitha Rajaram; Pankaj Garg; Robin Condliffe; Charlie A Elliot; A A Roger Thompson; Alexander M K Rothman; Athanasios Charalampopoulos; Allan Lawrie; Jim M Wild; Andrew J Swift; David G Kiely Journal: Front Cardiovasc Med Date: 2022-03-25
Authors: Rogério Souza; Marion Delcroix; Nazzareno Galié; Pavel Jansa; Sanjay Mehta; Tomás Pulido; Lewis Rubin; B K S Sastry; Gérald Simonneau; Olivier Sitbon; Adam Torbicki; Neli Boyanova; Liliya Chamitava; Claudia Stein; Richard N Channick Journal: Adv Ther Date: 2022-07-12 Impact factor: 4.070