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.

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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

The Fontan circulation is the optimal treatment for patients with univentricular hearts. These patients are at high risk of circulatory failure. There is no consensus on the optimal drug treatment for the prevention of failure of the Fontan circulation. The aim of this systematic review was to provide an overview of evidence for drug therapy used in the prevention of Fontan circulatory failure.

We searched the Embase database for articles that reported drug therapy in Fontan patients. Studies published between 1997 and 2014 were included if efficacy or safety of medication was assessed, drug therapy aimed to prevent or treat failure of the Fontan circulation, and if the full text was available. Case reports were excluded.

A total of nine studies were included with a total of 267 Fontan patients; four studies evaluated the medication sildenafil, one iloprost, three bosentan, and one enalapril. Among all, two sildenafil studies reported improvement in exercise capacity, one in exercise haemodynamics, and one in ventricular performance. In the largest study of bosentan, an increase in exercise capacity was found. Enalapril did not result in improvements.

The studies analysed in this review suggest that bosentan, sildenafil, and iloprost may improve exercise capacity at the short term. Given the limitations of the studies, more, larger, placebo-controlled studies with longer follow-up periods are needed to better understand which drug therapies are effective in the prevention of failure of the Fontan circulation.