Hostname: page-component-848d4c4894-ndmmz Total loading time: 0 Render date: 2024-06-02T08:15:21.265Z Has data issue: false hasContentIssue false
  • English
  • Français

Bosentan in the treatment of persistent pulmonary hypertension in newborns: a systematic review and meta-analysis

Published online by Cambridge University Press:  08 February 2024

Ning Gao ,
Yuanyuan Lv ,
Yanbin Cui Open the ORCID record for Yanbin Cui [Opens in a new window] ,
Pengchun Wang  and
Xin He
Ning Gao
Affiliation:
Neonatology Department, Baoding No.1 Central Hospital, Baoding, China
Yuanyuan Lv
Affiliation:
Infection control office, Baoding No.1 Central Hospital, Baoding, China
Yanbin Cui*
Affiliation:
Emergency Department, Baoding No.3 Central Hospital, Baoding, China
Pengchun Wang
Affiliation:
Neonatology Department, Baoding No.1 Central Hospital, Baoding, China
Xin He
Affiliation:
Neonatology Department, Baoding No.1 Central Hospital, Baoding, China
*
Corresponding author: Y. Cui; Email: cuiyanbin_cyb@163.com
Get access Rights & Permissions [Opens in a new window]

Abstract

Background:

Persistent pulmonary hypertension of the newborn is a life-threatening condition that affects about 1–2 per 1,000 live births worldwide. Bosentan is an oral dual endothelin receptor antagonist that may have a beneficial effect on persistent pulmonary hypertension of the newborn by reducing pulmonary vascular resistance and improving oxygenation. However, its role in persistent pulmonary hypertension of the newborn remains unclear.

Objectives:

To systematically evaluate the efficacy and safety of bosentan as an adjuvant therapy for persistent pulmonary hypertension of the newborn in newborns.

Methods:

We searched six English and two Chinese databases from their inception to 1 January 2023 following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We included randomised controlled trials and retrospective studies that compared bosentan with placebo or other drugs for persistent pulmonary hypertension of the newborn in newborns. We performed a meta-analysis using random-effects models and assessed the risk of bias and heterogeneity in the included studies.

Results:

We included 10 studies with a total of 550 participants. Bosentan significantly reduced the treatment failure rate (relative risk = 0.25, P < 0.001), pulmonary artery pressure (mean difference = −11.79, P < 0.001), and length of hospital stay (mean difference = −1.04, P = 0.003), and increased the partial pressure of oxygen (mean difference = 10.02, P < 0.001) and blood oxygen saturation (SpO2) (mean difference = 8.24, P < 0.001) compared with a placebo or other drugs. The occurrence of adverse reactions was not significantly different between bosentan and a placebo or other drugs.

Conclusions:

Bosentan is effective in the treatment of persistent pulmonary hypertension of the newborn but adverse reactions such as abnormal liver function should be observed when using it.

Keywords

bosentanpersistent pulmonary hypertensionnewborn
Type
Original Article
Information
Cardiology in the Young , First View , pp. 1 - 8
Check for updates
Copyright
© The Author(s), 2024. Published by Cambridge University Press

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

Abman, SH, Kinsella, JP, Rosenzweig, EB, et al. Implications of the U.S. food and drug administration warning against the use of sildenafil for the treatment of pediatric pulmonary hypertension. Am J Respir Crit Care Med 2013; 187: 572–575.CrossRefGoogle Scholar
Steinhorn, RH, Fineman, J, Kusic-Pajic, A, et al. Bosentan as adjunctive therapy for persistent pulmonary hypertension of the newborn: results of the randomized multicenter placebo-controlled exploratory trial. J Pediatr 2016; 177: 90–96.e3.CrossRefGoogle ScholarPubMed
Mourani, PM, Sontag, MK, Younoszai, A, et al. Early pulmonary vascular disease in preterm infants at risk for bronchopulmonary dysplasia. Am J Respir Crit Care Med 2015; 191: 87–95.CrossRefGoogle ScholarPubMed
Kinsella, JP, McQueston, JA, Rosenberg, AA, Abman, SH. Hemodynamic effects of exogenous nitric oxide in ovine transitional pulmonary circulation. Am J Physiol 1992; 263: H875–H880.Google ScholarPubMed
Giaid, A, Yanagisawa, M, Langleben, D, et al. Expression of endothelin-1 in the lungs of patients with pulmonary hypertension. N Engl J Med 1993; 328: 1732–1739.CrossRefGoogle ScholarPubMed
Mourani, PM, Ivy, DD, Rosenberg, AA, Fagan, TE, Abman, SH. Left ventricular diastolic dysfunction in bronchopulmonary dysplasia. J Pediatr 2008; 152: 291–293.CrossRefGoogle ScholarPubMed
Mourani, PM, Sontag, MK, Ivy, DD, Abman, SH. Effects of long-term sildenafil treatment for pulmonary hypertension in infants with chronic lung disease. J Pediatr 2009; 154: 379–384.e3842.CrossRefGoogle ScholarPubMed
Galiè, N, Beghetti, M, Gatzoulis, MA, et al. Bosentan therapy in patients with Eisenmenger syndrome: a multicenter, double-blind, randomized, placebo-controlled study. Circulation 2006; 114: 48–54.CrossRefGoogle ScholarPubMed
Galiè, N, Olschewski, H, Oudiz, RJ, et al. Ambrisentan for the treatment of pulmonary arterial hypertension: results of the ambrisentan in pulmonary arterial hypertension, randomized, double-blind, placebo-controlled, multicenter, efficacy (ARIES) study 1 and 2. Circulation 2008; 117: 3010–3019.CrossRefGoogle Scholar
Barst, RJ, Ivy, DD, Gaitan, G, et al. A randomized, double-blind, placebo-controlled, dose-ranging study of oral sildenafil citrate in treatment-naive children with pulmonary arterial hypertension. Circulation 2012; 125: 324–334.CrossRefGoogle ScholarPubMed
Bassler, D, Choong, K, McNamara, P, Kirpalani, H. Neonatal persistent pulmonary hypertension treated with milrinone: four case reports. Biol Neonate 2006; 89: 1–5.CrossRefGoogle ScholarPubMed
Barrington, KJ, Finer, NN. Inhaled nitric oxide for preterm infants: a systematic review. Pediatrics 2007; 120: 1088–1099.CrossRefGoogle ScholarPubMed
Chester, M, Seedorf, G, Tourneux, P, et al. Cinaciguat, a soluble guanylate cyclase activator, augments cGMP after oxidative stress and causes pulmonary vasodilation in neonatal pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol 2011; 301: L755–L764.CrossRefGoogle ScholarPubMed
Kinsella, JP, Cutter, GR, Walsh, WF, et al. Early inhaled nitric oxide therapy in premature newborns with respiratory failure. N Engl J Med 2006; 355: 354–364.CrossRefGoogle ScholarPubMed
Kinsella, JP, Ivy, DD, Abman, SH. Pulmonary vasodilator therapy in congenital diaphragmatic hernia: acute, late, and chronic pulmonary hypertension. Semin Perinatol 2005; 29: 123–128.CrossRefGoogle ScholarPubMed
Stocker, C, Penny, DJ, Brizard, CP, Cochrane, AD, Soto, R, Shekerdemian, LS. Intravenous sildenafil and inhaled nitric oxide: a randomised trial in infants after cardiac surgery. Intensive Care Med 2003; 29: 1996–2003.CrossRefGoogle ScholarPubMed
Kawut, SM, Taichman, DB, Ahya, VN, et al. Hemodynamics and survival of patients with portopulmonary hypertension. Liver Transpl 2005; 11: 1107–1111.CrossRefGoogle ScholarPubMed
Ramani, GV, Park, MH. Pharmacotherapy for pulmonary arterial hypertension. Heart Fail Clin 2012; 8: 385–402.CrossRefGoogle ScholarPubMed
Abman, SH, Hansmann, G, Archer, SL, et al. Pediatric pulmonary hypertension: guidelines from the American heart association and American thoracic society. Circulation 2015; 132: 2037–2099.CrossRefGoogle ScholarPubMed
Higgins JPT, Green S. Cochrane handbook for systematic reviews of interventions:version 5.1.0 (updated February). The Cochrane Collaboration, 2011. http://www.cochrane-handbook.org.Google Scholar
Wells A, Shea B, O’Connell D, et al. Thenewcastle-ottawa scale (NOS) for assessing the quality of nonrandomisedstudies in meta-analyses. [EB/OL]. (2012-06-15)[2014-01-13]. http://www.ohri.ca/programs/clinical_epidemiology/oxford.htm.Google Scholar
Mohamed, WA, Ismail, M. A randomized, double-blind, placebo-controlled, prospective study of bosentan for the treatment of persistent pulmonary hypertension of the newborn. J Perinatol 2012; 32: 608–613.CrossRefGoogle ScholarPubMed
Maneenil, G, Thatrimontrichai, A, Janjindamai, W, et al. Effect of bosentan therapy in persistent pulmonary hypertension of the newborn. Pediatr Neonatol 2018; 59: 58–64.CrossRefGoogle ScholarPubMed
Fatima, N, Arshad, S, Quddusi, AI, et al. Comparison of the efficacy of sildenafil alone versus sildenafil plus bosentan in newborns with persistent pulmonary hypertension. J Ayub Med Coll Abbottabad 2018; 30: 333–336.Google ScholarPubMed
Farhangdoust, S, Mehralizadeh, S, Bordbar, A. Comparison of the effects of bosentan and sildenafil in the treatment of persistent pulmonary arterial hypertension in infants. J Clin Neonatol 2020; 9: 249–254.Google Scholar
Vijay Kumar, JR, Natraj Setty, HS, Jayaranganath, M, et al. Efficacy, safety and tolerability of bosentan as an adjuvant to sildenafil and sildenafil alone in persistant pulmonary hypertension of newborn (PPHN). Interv Med Appl Sci 20216; 11: 216–220.Google Scholar
Wang, WL, Sun, YJ, Pi, YX. Therapeutic effect of bosentan and levocarnitine combined with sildenafil on pulmonary hypertension of the newborn. Hainan Med J 2019; 30: 2390–2393.Google Scholar
Li, GH, Bai, B. Efficacy and safety of bosentan combined with milrinone in the treatment of persistent pulmonary hypertension of the newborn. J Med Theory Pract 2020; 33: 111–112.Google Scholar
Li, K, Bai, B. Efficacy and safety of bosentan combined with milrinone in the treatment of persistent pulmonary hypertension of the newborn. Med Forum 2021; 25: 53–54.Google Scholar
Wang, SS, Kuang, ML, Zuo, etal XX. Effects of bosentan combined with treprostinil on red blood cell distribution width and serum melatonin in neonates with persistent pulmonary hypertension. J Pediatr Pharm 2021; 27: 1–3.Google Scholar
Pan, YY, Sun, YC, Zhao, CF, et al. Clinical observation of bosentan in the treatment of infants with congenital heart disease combined with pulmonary hypertension. J Shandong University 2016; 54: 56–57.Google Scholar
Qian, AM, Jiao, FF. Clinical observation of milrinone in the treatment of persistent pulmonary hypertension of newborn. China Pharm 2016; 27: 4993–4994,4995.Google Scholar
Li, XY, Shen, MP, Gong, HM, et al. Observation on the effect of high-frequency oscillatory ventilation combined with milrinone on persistent pulmonary hypertension of the newborn. Maternal Child Health Care China 2015; 30: 3096–3098.Google Scholar
Zhang, DZ, Zhang, XW, Chen, HY, et al. Long-term outcome of bosentan therapy in patients with pulmonary arterial hypertension associated with congenital heart diseases. Clin J Med Officers 2019; 47: 1073–1075,1080.Google Scholar
Goissen, C, Ghyselen, L, Tourneux, P, et al. Persistent pulmonary hypertension of the newborn with transposition of the great arteries: successful treatment with bosentan. Eur J Pediatr 2008; 167: 437–440.CrossRefGoogle ScholarPubMed
Nakwan, N, Choksuchat, D, Saksawad, R, et al. Successful treatment of persistent pulmonary hypertension of the newborn with bosentan. Acta Paediatr 2009; 98: 1683–1685.CrossRefGoogle ScholarPubMed
Radicioni, M, Bruni, A, Camerini, P. Combination therapy for life-threatening pulmonary hypertension in a premature infant: first report on bosentan use. Eur J Pediatr 2011; 170: 1075–1078.CrossRefGoogle Scholar
Humbert, M, Segal, ES, Kiely, DG, et al. Results of european post-marketing surveillance of bosentan in pulmonary hypertension. Eur Respir J 2007; 30: 338–344.CrossRefGoogle ScholarPubMed
Wolf, D, Tseng, N, Seedorf, G, et al. Endothelin-1 decreases endothelial PPARγ signaling and impairs angiogenesis after chronic intrauterine pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol 2014; 306: L361–L371.CrossRefGoogle ScholarPubMed