McLaughlin, V.V., Sitbon, O., Chin, K.M. et al. (11 more authors) (2024) Initial combination therapy with macitentan and tadalafil in patients with pulmonary arterial hypertension, with and without cardiac comorbidities. European Journal of Heart Failure, 26 (11). pp. 2379-2391. ISSN 1388-9842
Abstract
Aims
According to current guidelines, initial monotherapy should be considered for pulmonary arterial hypertension (PAH) patients with cardiopulmonary comorbidities. This analysis of combined data from the TRITON and REPAIR clinical trials, assesses efficacy and safety of initial double combination therapy in patients without vs. with 1–2 cardiac comorbidities.
Methods and results
Data were combined for patients from TRITON (NCT02558231) and REPAIR (NCT02310672) on initial macitentan and tadalafil double combination therapy (overall set, n = 148) and two subgroups defined as patients without cardiac comorbidities (n = 62) and those with 1–2 cardiac comorbidities (n = 78). Patients with ≥3 comorbidities were excluded from these studies. For the overall set, the median (Q1–Q3) duration of combined macitentan and tadalafil exposure was 513.0 (364.0–778.0) days, and was similar between subgroups. Change from baseline to Week 26 for pulmonary vascular resistance was −55% and −50% for patients without and with 1–2 cardiac comorbidities, respectively; marked improvements in other hemodynamic and functional parameters were also observed, although functional parameters improved to a lesser extent in patients with comorbidities. At Week 26, the majority of patients had improved PAH risk status, according to the non-invasive four-strata and REVEAL Lite 2.0 methods. The safety profile of initial macitentan plus tadalafil combination therapy was consistent with the known profiles of the two drugs, and similar between the subgroups.
Conclusions
Initial double combination therapy with macitentan plus tadalafil is efficacious in patients with PAH with 1–2 cardiac comorbidities and those without, with similar safety and tolerability profiles between the two groups.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2024 Actelion Pharmaceuticals Ltd. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
Keywords: | Pulmonary arterial hypertension; Risk stratification; Cardiac comorbidities; Macitentan; Tadalafil; Initial double combination therapy |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > School of Medicine and Population Health |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 08 Jul 2024 14:00 |
Last Modified: | 12 Mar 2025 12:21 |
Status: | Published |
Publisher: | Wiley |
Refereed: | Yes |
Identification Number: | 10.1002/ejhf.3319 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:214572 |