Effect of macitentan on cardiac function in pulmonary arterial hypertension: results from the repair echocardiography substudy

SESSION TITLE: Pulmonary Vascular Disease Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: October 18-21, 2020 PURPOSE: Pulmonary arterial hypertension (PAH) impacts the structure and function of the right ventricle (RV). The REPAIR study reported improvements in RV function, measured by cardiac MRI (cMRI), in macitentan-treated PAH patients. Here we report the effect of macitentan on RV function measured by echocardiography (echo) in a subgroup of patients enrolled in REPAIR. METHODS: REPAIR (NCT02310672) was a 52-week, multicenter, open-label, single-arm, phase 4 study assessing the effect of macitentan on RV function by cMRI and right heart catheterization in PAH patients. Macitentan 10 mg was initiated in treatment-naïve patients, in patients receiving stable background phosphodiesterase type-5 inhibitor (PDE5i) at baseline (BL), or in initial combination with PDE5i. Of the 87 patients treated in REPAIR, 46 were included in the echo subgroup. Echo (2D, M-mode and Doppler) was performed at BL, Weeks 26 and 52; all echocardiograms were centrally assessed and reviewers were blinded to patient identity and date/sequence of image acquisition. Changes from BL to Week 26 and Week 52 in key RV variables measured by echo are reported here. RESULTS: In the echo subgroup (N=46) 38 (83%) patients were female. At BL, median age was 45 years; median 6-minute walk distance was 389 (Q1=324, Q3=481) m; 30% and 70% of patients were WHO functional class II and III; 65% had idiopathic PAH. For key RV echo variables, mean change (95% CI) from BL to Week 26 was: -2.8 (-4.7, -0.8) mm, p=0.0071 for RV end diastolic dimension (RVEDD; N=43; BL mean 45.3 [SD=7.1] mm); +7.5 (+4.4, +10.7) %, p<0.0001 for RV fractional area change (RV FAC; N=42; BL mean 25.9 [SD=11.9] %); +11.6 (+3.2, +20.0) mL, p=0.0089 for RV stroke volume (RVSV; N=28; BL mean 68.4 [SD=22.6] mL); +0.5 (-0.1, +1.1) L/min, p=0.1152 for RV cardiac output (RVCO; N=28; BL mean 5.1 [SD=1.9] L/min); +2.5 (+1.4, +3.6) mm, p<0.0001 for tricuspid annular plane systolic excursion (TAPSE; N=39; BL mean 16.4 [SD=3.5] mm); +0.19 (+0.06, +0.32), p=0.0065 for the mitral E/A ratio (N=35; BL mean 0.95 [SD=0.35]); -3.0 (-4.7, -1.4) %, p=0.0006 for the 2D global longitudinal RV strain (N=36; BL mean 13.9 [SD=5.7] %); and -7 (-10, -4) bpm, p<0.0001 for heart rate (HR; N=43; BL mean 78 [SD=15] bpm). For parameters that were significantly different at Week 26, changes from BL were maintained at Week 52. For RVCO, the mean change at Week 52 (95% CI) was +0.8 (0.02, 1.6) L/min, p-value was 0.0457. CONCLUSIONS: In the REPAIR echo substudy, macitentan treatment was associated with significant improvements in RV function measured by echo at Week 26 and 52, including RVEDD, RVSV, TAPSE and RV strain, key prognostic markers in PAH. Normalization of the mitral flow (E/A ratio) suggests that these improvements in RV function are also associated with improved left ventricle diastolic function. CLINICAL IMPLICATIONS: This study furthers understanding of the effect of macitentan on RV function in PAH patients. DISCLOSURES: Advisory Committee Member relationship with Actelion Please note: $5001 - $20000 by Richard Channick, source=Admin input, value=Consulting fee Consultant relationship with Actelion Please note: $5001 - $20000 by Richard Channick, source=Admin input, value=Consulting fee Advisory Committee Member relationship with Arena Please note: $5001 - $20000 by Richard Channick, source=Admin input, value=Consulting fee Advisory Committee Member relationship with Bayer Please note: $5001 - $20000 by Richard Channick, source=Admin input, value=Consulting fee Advisory Committee Member relationship with United Therapeutics Please note: $5001 - $20000 Added 06/02/2020 by Richard Channick, source=Admin input, value=Consulting fee No relevant relationships Added 02/26/2020 by Emmanuelle Cottreel, source=Web Response, value=Salary Removed 02/26/2020 by Emmanuelle Cottreel, source=Web Response No relevant relationships Added 02/26/2020 by Emmanuelle Cottreel, source=Web Response, value=Salary Removed 02/26/2020 by Emmanuelle Cottreel, source=Web Response Speaker/Speaker's Bureau relationship with MSD Please note: $1-$1000 Added 05/18/2020 by Nazzareno Galie, source=Web Response, value=Consulting fee Grant/research support to my institution relationship with Actelion Pharmaceuticals Ltd Please note: $5001 - $20000 Added 05/28/2020 by Nazzareno Galie, source=Web Response, value=Grant/Research Support Grant/research support to my institution relationship with Bayer Healthcare Please note: $1001 - $5000 Added 05/28/2020 by Nazzareno Galie, source=Web Response, value=Consulting fee Grant/research support to my institution relationship with GlaxoSmithKline Please note: $5001 - $20000 Added 05/28/2020 by Nazzareno Galie, source=Web Response, value=Grant/Research Support Grant/research support to my institution relationship with Pfizer Please note: $1001 - $5000 Added 05/28/2020 by Nazzareno Galie, source=Web Response, value=Consulting fee Advisory Committee Member relationship with Actelion Please note: $1001 - $5000 Added 05/28/2020 by Nazzareno Galie, source=Web Response, value=Consulting fee Speaker/Speaker's relationship with Actelion Pharmaceuticals Please note: $5001 - $20000 Added 05/06/2020 by David Kiely, source=Web Response, value=Consulting fee Advisory Committee Member relationship with Actelion Pharmaceuticals Please note: $5001 - $20000 Added 05/06/2020 by David Kiely, source=Web Response, value=Consulting fee Advisory Committee Member relationship with GSK Please note: $1001 - $5000 Added 05/06/2020 by David Kiely, source=Web Response, value=Consulting fee Advisory Committee Member relationship with MSD Please note: $1001 - $5000 Added 05/06/2020 by David Kiely, source=Web Response, value=Consulting fee Speaker/Speaker's Bureau relationship with Bayer Please note: $1001 - $5000 Added 05/06/2020 by David Kiely, source=Web Response, value=Consulting fee Consultant relationship with Actelion Pharmaceuticals Please note: $5001 - $20000 Added 06/02/2020 by J Tim Marcus, source=Web Response, value=Consulting fee research support relationship with Actelion Pharmaceuticals France Please note: $1001 - $5000 Added 06/01/2020 by Pamela Moceri, source=Web Response, value=Grant/Research Support Advisory Committee Member relationship with Actelion Pharmaceuticals Please note: $5001 - $20000 Added 04/02/2020 by Andrew Peacock, source=Web Response, value=Personal fees Advisory Committee Member relationship with Pfizer Please note: $5001 - 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$20000 Added 07/17/2020 by Stephan Rosenkranz, source=Web Response, value=Consulting fee Speaker/Speaker's Bureau relationship with Vifor Please note: $1001 - $5000 Added 07/17/2020 by Stephan Rosenkranz, source=Web Response, value=Honoraria Consultant relationship with United Therapeutics Please note: $5001 - $20000 Added 07/17/2020 by Stephan Rosenkranz, source=Web Response, value=Consulting fee Consultant relationship with Actelion pharmaceuticals Please note: $5001 - $20000 Added 02/25/2020 by Andew Swift, source=Web Response, value=Consulting fee Advisory Committee Member relationship with Actelion Please note: $5001 - $20000 Added 05/07/2020 by Ahmed Tawakol, source=Web Response, value=Consulting fee Research funding to institution relationship with Genentech Please note: >$100000 Added 05/07/2020 by Ahmed Tawakol, source=Web Response, value=Grant/Research Support Advisory Committee Member relationship with Esperion Please note: $5001 - $20000 Added 05/07/2020 by Ahmed Tawakol, source=Web Response, value=Consulting fee Consultant relationship with Actelion Please note: $1001 - 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$5000 Added 02/25/2020 by Anton Vonk Noordegraaf, source=Web Response, value=Honoraria Consultant relationship with Actelion Please note: >$100000 Added 03/02/2020 by Graham Wetherill, source=Web Response, value=Consulting fee