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Clinical efficacy and safety of switch from bosentan to macitentan in children and young adults with pulmonary arterial hypertension: extended study results

Published online by Cambridge University Press:  15 April 2020

Ebru Aypar Open the ORCID record for Ebru Aypar [Opens in a new window] ,
Dursun Alehan ,
Tevfik Karagöz ,
Hakan Aykan  and
İlker Ertugrul
Ebru Aypar*
Affiliation:
Department of Pediatric Cardiology, Hacettepe University Faculty of Medicine, Ankara, Turkey
Dursun Alehan
Affiliation:
Department of Pediatric Cardiology, Hacettepe University Faculty of Medicine, Ankara, Turkey
Tevfik Karagöz
Affiliation:
Department of Pediatric Cardiology, Hacettepe University Faculty of Medicine, Ankara, Turkey
Hakan Aykan
Affiliation:
Department of Pediatric Cardiology, Hacettepe University Faculty of Medicine, Ankara, Turkey
İlker Ertugrul
Affiliation:
Department of Pediatric Cardiology, Hacettepe University Faculty of Medicine, Ankara, Turkey
*
Author for correspondence: Prof. Dr E. Aypar, Department of Pediatric Cardiology, Faculty of Medicine, Hacettepe University, Ankara, Turkey. Tel: +90 532 293 07 09; Fax: +90 312 305 50 00. E-mail: [email protected]
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Abstract

Background:

Macitentan is an orally active, potent, dual endothelin receptor antagonist and is the only registered treatment for pulmonary arterial hypertension that significantly reduced morbidity and mortality in a long-term study.

Aim:

We have recently reported that switch from bosentan to macitentan significantly improved exercise capacity in children and young adults with pulmonary arterial hypertension in a 24-week prospective study and well tolerated without adverse events. We now aimed to evaluate clinical efficacy, safety of switch in a larger patient population, in a 24-month prospective study.

Methods:

This is a single-institution, 24-month prospective study. Patients ≥12 years with idiopathic/heritable, pulmonary arterial hypertension, or related to CHD or residual pulmonary arterial hypertension due to repaired congenital systemic-to-pulmonary shunts and on bosentan treatment were included. Concomitant treatment with oral phosphodiesterase type 5 inhibitors/inhaled prostanoids was allowed. Outcome measures included change from baseline to 24 months, in the 6-minute walk distance, functional class, oxygen saturation at rest/after walk distance test, and natriuretic peptide levels. Safety end points included adverse events, laboratory abnormalities.

Results:

Twenty-seven patients (19 adults/8 children, mean age: 21.1 ± 6.3 years (12–36), weight: 53.1 ± 15.7 kgs (26–87)) were included. Mean duration of macitentan treatment: 22.3 ± 3.9 months (9–24). Six-minute walk distance significantly improved from baseline (mean: 458 ± 79 m (300–620)) at 6 months (mean: 501 ± 73 m (325–616) + 43 m) (p < 0.05), at 12 months (mean: 514 ± 82 m (330–626) + 56 m) (p < 0.05), and at 24 months (mean: 532 ± 85 m (330–682) + 74 m) (p < 0.05). We observed a significant improvement during the first 6 months but no incremental improvement after 6 months (p > 0.05). Macitentan did not significantly change functional class, oxygen saturation, and natriuretic levels (p > 0.05). None of the patients had anaemia, hepatotoxicity, and peripheral edema.

Conclusions:

Our study is the first study which showed that switch from bosentan to macitentan improved exercise capacity in children and young adults with pulmonary arterial hypertension significantly in the first 6 months and compared to baseline in 24 months and well tolerated without adverse events.

Keywords

Bosentanchildrenendothelin receptor antagonistmacitentanpulmonary arterial hypertension
Type
Original Article
Information
Cardiology in the Young , Volume 30 , Issue 5 , May 2020 , pp. 681 - 685
Copyright
© The Author(s) 2020. Published by Cambridge University Press

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