Safety and efficacy of the endothelin receptor antagonist macitentan in pediatric pulmonary hypertension
2020 Cardiovascular Diagnosis and Therapy. All rights reserved..
BACKGROUND: Macitentan, a dual endothelin receptor antagonist (ERA), was approved in 2014 for the treatment of adults with idiopathic pulmonary arterial hypertension (PAH). Once-per-day dosing and low potential hepatic toxicity make macitentan an appealing therapeutic option for children with PAH, but reports on its use in pediatric patients are still lacking.
METHODS: Prospective observational study of 18 children [10 male; median age: 8.5, minimum (min.): 0.6, maximum (max.): 16.8 years] with pulmonary hypertension (PH). Four of these 18 patients were treatment-naïve and started on a de novo macitentan therapy. The remaining 14/18 children were already on a PH-targeted pharmacotherapy (sildenafil or bosentan as monotherapy or in combination). Nine children who were on bosentan were switched to macitentan. We analyzed the 6-minute walking distance (6MWD), NYHA functional class (FC)/modified ROSS score, invasive hemodynamics, echocardiographic variables and the biomarker N-terminal pro-brain natriuretic peptide (NT-proBNP).
RESULTS: The median follow up was 6 months (min.: 0.5, max.: 30). Macitentan treatment was associated with improvement of invasive hemodynamics, e.g., the ratio of mean pulmonary arterial pressure/mean systemic arterial pressure decreased from a median of 62% (min.: 30%, max.: 87%) to 49% (min.: 30%, max.: 69%), P<0.05; pulmonary vascular resistance index (PVRi) decreased from a median of 7.6 (min.: 3.3, max.: 11.5) to 4.8 Wood units × m2 body surface area (min.: 2.5, max.: 10), P<0.05. The tricuspid annular plane systolic excursion (TAPSE) increased from a median of 1.4 (min.: 0.8, max.: 2.8) to 1.9 (min.: 0.8, max.: 2.7) cm, (P<0.05). NT-proBNP values decreased from a median of 272 (min.: 27, max.: 2,010) to 229 (min.: 23, max.: 814) pg/mL under macitentan therapy (P<0.05). The 6MWD and NYHA FC/modified ROSS score did not change significantly.
CONCLUSIONS: This is the first prospective study of macitentan pharmacotherapy in infants and children with PH <12 years of age. Except in one patient, macitentan treatment was well tolerated and was associated with improvements in invasive hemodynamics, longitudinal systolic RV function (TAPSE) and serum NT-proBNP values.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:10 |
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| Enthalten in: |
Cardiovascular diagnosis and therapy - 10(2020), 5 vom: 17. Okt., Seite 1675-1685 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Schweintzger, Sabrina [VerfasserIn] |
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| Links: |
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| Themen: |
Bosentan |
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| Anmerkungen: |
Date Revised 18.04.2022 published: Print Citation Status PubMed-not-MEDLINE |
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| doi: |
10.21037/cdt.2020.04.01 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM317917803 |
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| 500 | |a Date Revised 18.04.2022 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a 2020 Cardiovascular Diagnosis and Therapy. All rights reserved. | ||
| 520 | |a BACKGROUND: Macitentan, a dual endothelin receptor antagonist (ERA), was approved in 2014 for the treatment of adults with idiopathic pulmonary arterial hypertension (PAH). Once-per-day dosing and low potential hepatic toxicity make macitentan an appealing therapeutic option for children with PAH, but reports on its use in pediatric patients are still lacking | ||
| 520 | |a METHODS: Prospective observational study of 18 children [10 male; median age: 8.5, minimum (min.): 0.6, maximum (max.): 16.8 years] with pulmonary hypertension (PH). Four of these 18 patients were treatment-naïve and started on a de novo macitentan therapy. The remaining 14/18 children were already on a PH-targeted pharmacotherapy (sildenafil or bosentan as monotherapy or in combination). Nine children who were on bosentan were switched to macitentan. We analyzed the 6-minute walking distance (6MWD), NYHA functional class (FC)/modified ROSS score, invasive hemodynamics, echocardiographic variables and the biomarker N-terminal pro-brain natriuretic peptide (NT-proBNP) | ||
| 520 | |a RESULTS: The median follow up was 6 months (min.: 0.5, max.: 30). Macitentan treatment was associated with improvement of invasive hemodynamics, e.g., the ratio of mean pulmonary arterial pressure/mean systemic arterial pressure decreased from a median of 62% (min.: 30%, max.: 87%) to 49% (min.: 30%, max.: 69%), P<0.05; pulmonary vascular resistance index (PVRi) decreased from a median of 7.6 (min.: 3.3, max.: 11.5) to 4.8 Wood units × m2 body surface area (min.: 2.5, max.: 10), P<0.05. The tricuspid annular plane systolic excursion (TAPSE) increased from a median of 1.4 (min.: 0.8, max.: 2.8) to 1.9 (min.: 0.8, max.: 2.7) cm, (P<0.05). NT-proBNP values decreased from a median of 272 (min.: 27, max.: 2,010) to 229 (min.: 23, max.: 814) pg/mL under macitentan therapy (P<0.05). The 6MWD and NYHA FC/modified ROSS score did not change significantly | ||
| 520 | |a CONCLUSIONS: This is the first prospective study of macitentan pharmacotherapy in infants and children with PH <12 years of age. Except in one patient, macitentan treatment was well tolerated and was associated with improvements in invasive hemodynamics, longitudinal systolic RV function (TAPSE) and serum NT-proBNP values | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Bosentan | |
| 650 | 4 | |a child | |
| 650 | 4 | |a endothelin receptor antagonist (ERA) | |
| 650 | 4 | |a macitentan | |
| 650 | 4 | |a pulmonary hypertension (PH) | |
| 700 | 1 | |a Koestenberger, Martin |e verfasserin |4 aut | |
| 700 | 1 | |a Schlagenhauf, Axel |e verfasserin |4 aut | |
| 700 | 1 | |a Grangl, Gernot |e verfasserin |4 aut | |
| 700 | 1 | |a Burmas, Ante |e verfasserin |4 aut | |
| 700 | 1 | |a Kurath-Koller, Stefan |e verfasserin |4 aut | |
| 700 | 1 | |a Pocivalnik, Mirjam |e verfasserin |4 aut | |
| 700 | 1 | |a Sallmon, Hannes |e verfasserin |4 aut | |
| 700 | 1 | |a Baumgartner, Daniela |e verfasserin |4 aut | |
| 700 | 1 | |a Hansmann, Georg |e verfasserin |4 aut | |
| 700 | 1 | |a Gamillscheg, Andreas |e verfasserin |4 aut | |
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