Key result
In pediatric pulmonary arterial hypertension, endothelin receptor antagonists (bosentan) significantly reduced the duration of mechanical ventilation compared to phosphodiesterase type 5 inhibitors (sildenafil) (WMD -157.04).
Why the study?
Although advances have been made in PAH-targeted medications for pediatric patients, the efficacy and safety of these treatments remain controversial.
Do endothelin receptor antagonists, phosphodiesterase type 5 inhibitors, and prostaglandins improve clinical, respiratory, and hemodynamic outcomes in pediatric pulmonary arterial hypertension?
Network Meta-Analysis (n=1,574)
Do endothelin receptor antagonists, phosphodiesterase type 5 inhibitors, and prostaglandins improve clinical, respiratory, and hemodynamic outcomes in pediatric pulmonary arterial hypertension?
Mean Difference: -157.04 (95% CI -173.88–-106.11)
In pediatric pulmonary arterial hypertension, ERAs and prostaglandins effectively shorten mechanical ventilation and ICU stays, while PDE-5 inhibitors like sildenafil may best reduce the risk of pulmonary hypertension crises.
Supports bosentan over sildenafil to shorten ventilation in pediatric PAH; extends meta-analytic evidence to children.
Background: Pulmonary arterial hypertension (PAH) is a fatal disease characterized by pulmonary vascular remodeling and increased pulmonary artery pressure, leading to impaired lung oxygenation, right heart failure, and even death. Although great advances have been made in PAH-targeted medications for pediatric patients, the efficacy and safety of these treatments are controversial. Methods: We retrieved relevant articles from electronic databases including PubMed, EMBASE, Web of Science, and Cochrane Library until 12 April 2022. To compare the effectiveness and safety of endothelin receptor antagonists (ERAs), phosphodiesterase type 5 Inhibitors (PDE-5i), and prostaglandins (ProA) in the treatment of pediatric PAH, we investigated six hemodynamic parameters, four respiratory parameters, intensive care unit (ICU) stay duration, length of hospital stay, and two safety outcomes. Results: A total of 27 randomized controlled trials (RCTs) were included in the meta-analysis with 1,574 pediatric participants. The duration of mechanical ventilation was shorter for patients using bosentan, sildenafil, and ProsA, compared with that for patients using the placebo. Bosentan helped to shorten more time for mechanical ventilation than ProsA did, while ProsA was more effective than sildenafil in this respect. As for the length of stay in the ICU, patients administered by ProsA or sildenafil needed shorter ICU stay, compared to those using the placebo, while ProsA was more effective for shortening ICU stay time. In light of safety outcomes, there was a statistically significant difference between the sildenafil and the placebo group. Sildenafil surpassed ProsA in reducing the incidence of pulmonary hypertension (PH) crisis. Conclusions: ERAs were more effective than ProsA in shortening the duration of mechanical ventilation, while ProsA were better for shortening the duration of mechanical ventilation and ICU stay than PDE-5i. PDE-5i were found to generate more benefits in decreasing the occurrence of PH crisis, though further investigation is warranted. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=351505.
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Cao et al. (2023) conducted a network meta-analysis in Pediatric pulmonary arterial hypertension (n=1,574). Endothelin receptor antagonists, phosphodiesterase type 5 inhibitors, and prostaglandins vs. Placebo or active comparators was evaluated on Duration of mechanical ventilation (Bosentan vs Sildenafil) (WMD -157.04, 95% CI -173.88 to -106.11). In pediatric pulmonary arterial hypertension, endothelin receptor antagonists (bosentan) significantly reduced the duration of mechanical ventilation compared to phosphodiesterase type 5 inhibitors (sildenafil) (WMD -157.04).
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