Initial combination therapy with macitentan and tadalafil in patients with pulmonary arterial hypertension, with and without cardiac comorbidities,European Journal of Heart Failure

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Initial combination therapy with macitentan and tadalafil in patients with pulmonary arterial hypertension, with and without cardiac comorbidities
European Journal of Heart Failure ( IF 16.9 ) Pub Date : 2024-07-05 , DOI: 10.1002/ejhf.3319
Vallerie V McLaughlin ₁ , Olivier Sitbon ₂ , Kelly M Chin ₃ , Nazzareno Galiè _{4,

5} , Marius M Hoeper ₆ , David G Kiely ₇ , Gwen MacDonald ₈ , Nicolas Martin ₉ , Stephen C Mathai ₁₀ , Andrew Peacock ₁₁ , Ahmed Tawakol ₁₂ , Adam Torbicki ₁₃ , Anton Vonk Noordegraaf ₁₄ , Stephan Rosenkranz ₁₅

Affiliation

University of Michigan, Ann Arbor, MI, USA.
Université Paris-Saclay, Hôpital Bicêtre, Le Kremlin Bicêtre, France.
UT Southwestern Medical Center, Dallas, TX, USA.
Cardiology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
Dipartimento DIMEC, Università di Bologna, Bologna, Italy.
Hannover Medical School and German Centre for Lung Research, Hannover, Germany.
Sheffield Pulmonary Vascular Disease Unit, NIHR Biomedical Research Centre Sheffield and University of Sheffield, Sheffield, UK.
Actelion Pharmaceuticals Ltd, a Johnson & Johnson Company, Global Medical Affairs, Allschwil, Switzerland.
Actelion Pharmaceuticals Ltd, a Johnson & Johnson Company, Statistical Decision Science, Allschwil, Switzerland.
Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Scottish Pulmonary Vascular Unit, Glasgow, UK.
Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Department of Pulmonary Circulation, Thromboembolic Diseases and Cardiology, Centre of Postgraduate Medical Education, ECZ-Otwock, ERN-LUNG Member, Otwock, Poland.
Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Department of Cardiology, Heart Center at the University Hospital Cologne, and Cologne Cardiovascular Research Center (CCRC), University of Cologne, Cologne, Germany.

AimsAccording 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 resultsData 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.ConclusionsInitial 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.

中文翻译：

对于患有或不患有心脏合并症的肺动脉高压患者，马西腾坦和他达拉非的初始联合治疗

目的根据目前的指南，患有心肺合并症的肺动脉高压（PAH）患者应考虑初始单一治疗。这项分析对 TRITON 和 REPAIR 临床试验的合并数据进行了评估，评估了初始双联合治疗对没有 1-2 种心脏合并症的患者与患有 1-2 种心脏合并症的患者的疗效和安全性。方法和结果合并了 TRITON (NCT02558231) 和 REPAIR (NCT02310672) 患者的数据）初始马西腾坦和他达拉非双联合治疗（总体组， n = 148）和两个亚组定义为没有心脏合并症的患者（ n = 62) 以及患有 1-2 种心脏合并症的患者 ( n = 78）。患有 ≥3 种合并症的患者被排除在这些研究之外。对于整个组，马西腾坦和他达拉非联合暴露的中位持续时间（Q1-Q3）为 513.0（364.0-778.0）天，亚组之间相似。对于没有和有 1-2 种心脏合并症的患者，肺血管阻力从基线到第 26 周的变化分别为 -55% 和 -50%；还观察到其他血流动力学和功能参数的显着改善，尽管患有合并症的患者功能参数改善程度较小。根据无创四层和 REVEAL Lite 2.0 方法，第 26 周时，大多数患者 PAH 风险状态有所改善。初始马西替坦加他达拉非联合治疗的安全性与两种药物的已知情况一致，并且亚组之间相似。结论马西替坦加他达拉非的初始双联合治疗对于患有 1-2 种心脏合并症和不患有心脏合并症的 PAH 患者有效，两组之间具有相似的安全性和耐受性。

更新日期：2024-07-05

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