Hostname: page-component-848d4c4894-sjtt6 Total loading time: 0 Render date: 2024-06-30T22:30:18.343Z Has data issue: false hasContentIssue false
  • English
  • Français

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

Published online by Cambridge University Press:  13 December 2017

Ebru Aypar ,
Dursun Alehan ,
Tevfik Karagöz ,
Hayrettin Hakan Aykan  and
İlker Ertugrul
Ebru Aypar*
Affiliation:
Department of Pediatric Cardiology, Hacettepe University, Sihhiye, Ankara, Turkey
Dursun Alehan
Affiliation:
Department of Pediatric Cardiology, Hacettepe University, Sihhiye, Ankara, Turkey
Tevfik Karagöz
Affiliation:
Department of Pediatric Cardiology, Hacettepe University, Sihhiye, Ankara, Turkey
Hayrettin Hakan Aykan
Affiliation:
Department of Pediatric Cardiology, Hacettepe University, Sihhiye, Ankara, Turkey
İlker Ertugrul
Affiliation:
Department of Pediatric Cardiology, Hacettepe University, Sihhiye, Ankara, Turkey
*
Correspondence to: Department of Pediatric Cardiology, Hacettepe University, Ankara, Såhhåye, Turkey. Tel: +90 (312) 305 11 57; Fax: +90 (312) 324 49 90; E-mail: ebruaypar@gmail.com
Get access Rights & Permissions [Opens in a new window]

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 event-driven study.

Aim

Few studies compared the clinical efficacy and safety of switch from bosentan to macitentan only in adult patients with pulmonary arterial hypertension. We aimed to evaluate the clinical efficacy and safety of switch from bosentan to macitentan in children and young adults.

Methods

This is a single-institution, 24-week prospective study. Patients ⩾12 years of age 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 therapy were included. Concomitant treatment with oral phosphodiesterase type 5 inhibitors and inhaled prostanoids was allowed. Outcome measures included change from baseline to week 24, in the 6-minute walk distance, functional class, oxygen saturation at rest/after 6-minute walk distance test, systolic pulmonary artery pressure estimated by echocardiography, and brain natriuretic peptide levels. Safety end points included adverse events laboratory abnormalities.

Results

A total of 13 patients – 5 male and 8 female – completed the study. The mean age was 20.3±6.5 years (12–35) and weight was 54.0±14.5 kg (27–75). Five patients were ⩽18 years of age. Macitentan improved 6-minute walk distance from baseline (mean: 466±35 m (300–590)), at 12 weeks (mean: 494±78 m (325–590), +28 m) (p<0.05), and at 24 weeks (mean: 507±58 m (325–625), +41 m) (p<0.05). Macitentan did not significantly change functional class, oxygen saturation at rest/after 6-minute walk distance test, brain natriuretic levels, and systolic pulmonary artery pressure (p>0.05). None of the patients had anaemia, hepatotoxicity, and peripheral oedema.

Conclusions

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

Keywords

Bosentanchildrenendothelin receptor antagonistmacitentanpulmonary arterial hypertension
Type
Original Articles
Information
Cardiology in the Young , Volume 28 , Issue 4 , April 2018 , pp. 542 - 547
Check for updates
Copyright
© Cambridge University Press 2017 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1. Galiè, N, Humbert, M, Vachiery, JL, et al. 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT). Eur Respir J 2015; 46: 903–975.CrossRefGoogle Scholar
2. Benza, RL, Miller, DP, Barst, RJ, Badesch, DB, Frost, AE, McGoon, MD. An evaluation of long-term survival from time of diagnosis in pulmonary arterial hypertension from REVEAL. Chest 2012; 142: 448–456.Google Scholar
3. Channick, RN, Simonneau, G, Sitbon, O, et al. Effects of the dual endothelin receptor antagonist bosentan in patients with pulmonary hypertension: a randomised placebo-controlled study. Lancet 2001; 358: 1119–1123.Google Scholar
4. Olschewski, H, Simonneau, G, Galiè, N, et al. Inhaled iloprost for severe pulmonary hypertension. N Engl J Med 2002; 347: 322–329.Google Scholar
5. Rubin, LJ, Badesch, DB, Barst, RJ, et al. Bosentan therapy for pulmonary arterial hypertension. N Engl J Med 2002; 346: 896–903.Google Scholar
6. Galiè, N, Badesch, BD, Oudiz, R, et al. Ambrisentan therapy for pulmonary arterial hypertension. J Am Coll Cardiol 2005; 46: 529–535.Google Scholar
7. Galiè, N, Ghofrani, HA, Torbicki, A, et al. Sildenafil citrate therapy for pulmonary arterial hypertension. N Engl J Med 2005; 353: 2148–2157; (Erratum, N Engl J Med 2006;354:2400–2401).Google Scholar
8. Galiè, N, Brundage, B, Ghofrani, A, et al. Tadalafil therapy for pulmonary arterial hypertension. Circulation 2009; 119: 2894–2903; (Erratum, Circulation 2011;124:e279).Google Scholar
9. Pulido, T, Adzerikho, I, Channick, RN, et al. Macitentan and morbidity and mortality in pulmonary arterial hypertension. N Engl J Med 2013; 369: 809–818.Google Scholar
10. Bolli, MH, Boss, C, Binkert, C, et al. The discovery of N-[5-(4-bromophenyl)-6-[2-[(5-bromo-2-pyrimidinyl)oxy]ethoxy]-4-pyrimidinyl]-N′-propylsulfamide (macitentan), an orally active, potent dual endothelin receptor antagonist. J Med Chem 2012; 55: 7849–7861.Google Scholar
11. Iglarz, M, Binkert, C, Morrison, K, et al. Pharmacology of macitentan, an orally active tissue-targeting dual endothelin receptor antagonist. J Pharmacol Exp Ther 2008; 327: 736–745.Google Scholar
12. Gatfield, J, Mueller Grandjean, C, Sasse, T, et al. Slow receptor dissociation kinetics differentiate macitentan from other endothelin receptor antagonists in pulmonary arterial smooth muscle cells. PLoS One 2012; 7: e47662.Google Scholar
13. Keating, GM. Macitentan: a review in pulmonary arterial hypertension. Am J Cardiovasc Drugs 2016; 16: 453–460.CrossRefGoogle ScholarPubMed
14. Dingemanse, J, Sidharta, PN, Maddrey, WC, et al. Efficacy, safety and clinical pharmacology of macitentan in comparison to other endothelin receptor antagonists in the treatment of pulmonary arterial hypertension. Expert Opin Drug Saf 2014; 13: 391–495.Google Scholar
15. Actelion Pharmaceuticals US Inc. Opsumit® (macitentan) tablets, for oral use: US prescribing information. 2016. http://opsumit.com/.Google Scholar
16. European Medicines Agency. Opsumit (macitentan): EU summary of product characteristics. 2016. http://www.ema.europa.eu/.Google Scholar
17. Blok, IM, van Riel, AC, van Dijk, AP, Mulder, BJ, Bouma, BJ. From bosentan to macitentan for pulmonary arterial hypertension and adult congenital heart disease: further improvement? Int J Cardiol 2017; 227: 51–52.CrossRefGoogle ScholarPubMed
18. Safdar, Z, Thakur, A, Frost, A. Tolerability of switch to macitentan from bosentan in pulmonary arterial hypertension. South Med J 2017; 110: 223–228.Google Scholar