Hostname: page-component-78c5997874-m6dg7 Total loading time: 0 Render date: 2024-11-12T10:00:42.532Z Has data issue: false hasContentIssue false
  • English
  • Français

Safety and effect of sildenafil on treating paediatric pulmonary arterial hypertension: a meta-analysis on the randomised controlled trials

Published online by Cambridge University Press:  20 October 2020

Qingyou Zhang ,
Bowen Xu Open the ORCID record for Bowen Xu [Opens in a new window] ,
Jichen Lv ,
Zhijian Wang  and
Junbao Du
Qingyou Zhang
Affiliation:
Department of Paediatrics, Peking University First Hospital, Beijing100034, China
Bowen Xu
Affiliation:
Department of Paediatrics, Peking University First Hospital, Beijing100034, China
Jichen Lv
Affiliation:
Department of Paediatrics, Peking University First Hospital, Beijing100034, China
Zhijian Wang
Affiliation:
Department of Paediatrics, Peking University First Hospital, Beijing100034, China
Junbao Du*
Affiliation:
Department of Paediatrics, Peking University First Hospital, Beijing100034, China
*
Author for correspondence: Professor Junbao Du, Department of Paediatrics, Peking University First Hospital, Xi-An Men Street No. 1, West District, Beijing100034, China. Tel: +8610-83573238; Fax: +8610-66530532. E-mail: junbaodu1@126.com
Get access Rights & Permissions [Opens in a new window]

Abstract

Background:

Efficacy of sildenafil in treating paediatric pulmonary arterial hypertension is controversial. This systematic review aimed to explore the safety and effect of sildenafil on treating paediatric pulmonary arterial hypertension (PAH) through meta-analysis.

Methods and results:

In this study, the electronic databases, including the Cochran Library database, EMBASE, and MEDLINE were systemically retrieved to identify the related randomised controlled trials (RCTs). Two reviewers had independently completed study selection, data collection, and assessment of the bias risk. Amongst 938 articles researched according to our retrieval strategy, 15 papers that involved 673 cases had been screened. Relative to control group, the sildenafil group had markedly reduced mortality (RR = 0.25, 95% CI: 0.12–0.51; p < 0.0001), but difference within the mortality was not statistically significant between high- and low-dose sildenafil groups (p = 0.152). Nonetheless, difference of the mean pulmonary arterial pressure between sildenafil as well as control group was of no statistical significance. Differences in the length of hospital stay and the incidences of pulmonary hypertensive crisis between children with PAH and controls were of no statistical significance. However, the summary estimate favoured that sildenafil reduced the duration of mechanical ventilation time, as well as the length of ICU stay and inotropic support.

Conclusions:

Sildenafil therapy reduces the mortality of PAH patients, but its effects on the haemodynamic outcomes and other clinical outcomes are still unclear.

Keywords

Sildenafilpaediatric pulmonary arterial hypertensioneffectsafetymortalitymeta-analysis
Type
Original Article
Information
Cardiology in the Young , Volume 30 , Issue 12 , December 2020 , pp. 1882 - 1889
Check for updates
Copyright
© The Author(s), 2020. 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.)

Footnotes

Qingyou Zhang and Bowen Xu contributed to this work equally.

References

Humbert, M, Morrell, NW, Archer, SL, et al. Cellular and molecular pathobiology of pulmonary arterial hypertension. J Am Coll Cardiol 2004; 43: 13s–24s.CrossRefGoogle ScholarPubMed
Rosenzweig, EB, Abman, SH, Adatia, I, et al. Paediatric pulmonary arterial hypertension: updates on definition, classification, diagnostics and management. Eur Respir J 2019; 53: 1–18.CrossRefGoogle ScholarPubMed
Humbert, M, Trembath, RC. Genetics of pulmonary hypertension: from bench to bedside. Eur Respir J 2002; 20: 741–749.CrossRefGoogle ScholarPubMed
D’Alonzo, GE, Barst, RJ, Ayres, SM, et al. Survival in patients with primary pulmonary hypertension. Results from a national prospective registry. Ann Intern Med 1991; 115: 343–349.CrossRefGoogle ScholarPubMed
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
Hansmann, G, Apitz, C, Abdul-Khaliq, H, et al. Executive summary: expert consensus statement on the diagnosis and treatment of paediatric pulmonary hypertension: the European Paediatric Pulmonary Vascular Disease Network, endorsed by ISHLT and DGPK. Heart 2016; 102 (Suppl 2): ii86–100.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, JP, Thompson, SG, Deeks, JJ, et al. Measuring inconsistency in meta-analyses. BMJ 2003; 327: 557–560.CrossRefGoogle ScholarPubMed
Barst, RJ, Beghetti, M, Pulido, T, et al. STARTS-2: long-term survival with oral sildenafil monotherapy in treatment-naive pediatric pulmonary arterial hypertension. Circulation 2014; 129: 1914–1923.CrossRefGoogle ScholarPubMed
Galiè, N, Ghofrani, HA, Torbicki, A, et al. Sildenafil citrate therapy for pulmonary arterial hypertension. N Engl J Med 2005; 353: 2148–2157.CrossRefGoogle ScholarPubMed
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
Vizza, CD, Sastry, BK, Safdar, Z, et al. Efficacy of 1, 5, and 20 mg oral sildenafil in the treatment of adults with pulmonary arterial hypertension: a randomized, double-blind study with open-label extension. BMC Pulm Med 2017; 17: 44.CrossRefGoogle ScholarPubMed
Hansmann, G Pulmonary hypertension in infants, children, and young adults. J Am Coll Cardiol 2017; 69: 2551–2569.CrossRefGoogle ScholarPubMed
Bai, Y, Sun, L, Hu, S, et al. Combination therapy in pulmonary arterial hypertension: a meta-analysis. Cardiology 2011; 120: 157–165.CrossRefGoogle ScholarPubMed
Hoeper, MM, Markevych, I, Spiekerkoetter, E, et al. Goal-oriented treatment and combination therapy for pulmonary arterial hypertension. Eur Respir J 2005; 26: 858–863.CrossRefGoogle ScholarPubMed
Roldan, T, Deiros, L, Romero, JA, et al.. Safety and tolerability of targeted therapies for pulmonary hypertension in children. Pediatr Cardiol 2014; 35: 490–498.CrossRefGoogle ScholarPubMed
Ploegstra, MJ, Berger, RM. What’s the end-point? Eur Respir J 2015; 45: 854–855.CrossRefGoogle ScholarPubMed
Galiè, N, Humbert, M, Vachiery, JL, et al. ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Respir J 2015; 46: 903–975. CrossRefGoogle ScholarPubMed
Sabri, MR, Bigdelian, H, Hosseinzadeh, M, et al.. Comparison of the therapeutic effects and side effects of tadalafil and sildenafil after surgery in young infants with pulmonary arterial hypertension due to systemic-to-pulmonary shunts. Cardiol Young 2017; 27: 1686–1693.CrossRefGoogle ScholarPubMed
Bhasin, S, Gogia, P, Nair, R, et al. Perioperative sildenafil therapy for children with ventricular septal defects and associated pulmonary hypertension undergoing corrective surgery: a randomised clinical trial. Indian J Anaesth 2017; 61: 798–802.CrossRefGoogle ScholarPubMed
Al Omar, S, Salama, H, Al Hail, M, et al. Effect of early adjunctive use of oral sildenafil and inhaled nitric oxide on the outcome of pulmonary hypertension in newborn infants: a feasibility study. J Neonatal Perinatal Med 2016; 9: 251–259.CrossRefGoogle ScholarPubMed
Sharma, VK, Joshi, S, Joshi, A, et al.. Does intravenous sildenafil clinically ameliorate pulmonary hypertension during perioperative management of congenital heart diseases in children? - a prospective randomized study. Ann Card Anaesth 2015; 18: 510–516.CrossRefGoogle ScholarPubMed
Xia, YL, Yan, WX, Chen, H. Efficacy and safety of sildenafil in the treatment of high altitude heart disease associated with severe pulmonary arterial hypertension in children: a preliminary evaluation. Chinese J Cont Pediatr 2014; 16: 745–748.Google ScholarPubMed
Palii, I, Vataman, E, Revenco, N, et al. O-024 outcome research in 77 patients with pulmonary arterial hypertension receiving sildenafil: a double-blind, randomised controlled study. Arch Dis Child 2014; 99 (Suppl 2): A31–A31.CrossRefGoogle Scholar
Farah, P, Ahmad-Ali, A, Hanane, G, et al. Additive effect of phosphodiesterase inhibitors in control of pulmonary hypertension after congenital cardiac surgery in children. Iran J Pediatr 2013; 23: 19–26.Google ScholarPubMed
El Midany, AA, Mostafa, EA, Azab, S, et al. Perioperative sildenafil therapy for pulmonary hypertension in infants undergoing congenital cardiac defect closure. Interact Cardiovasc Thorac Surg 2013; 17: 963–968.CrossRefGoogle ScholarPubMed
Vassalos, A, Peng, E, Young, D, et al. Pre-operative sildenafil and pulmonary endothelial-related complications following cardiopulmonary bypass: a randomised trial in children undergoing cardiac surgery. Anaesthesia 2011; 66: 472–480.CrossRefGoogle ScholarPubMed
Uslu, S, Kumtepe, S, Bulbul, A, et al. A comparison of magnesium sulphate and sildenafil in the treatment of the newborns with persistent pulmonary hypertension: a randomized controlled trial. J Trop Pediatr 2011; 57: 245–250.CrossRefGoogle ScholarPubMed
Fraisse, A, Butrous, G, Taylor, MB, et al. Intravenous sildenafil for postoperative pulmonary hypertension in children with congenital heart disease. Intensive Care Med 2011; 37: 502–509.CrossRefGoogle ScholarPubMed
Vargas-Origel, A, Gomez-Rodriguez, G, Aldana-Valenzuela, C, et al. The use of sildenafil in persistent pulmonary hypertension of the newborn. Am J Perinatol 2010; 27: 225–230.CrossRefGoogle ScholarPubMed
Peiravian, F, Amirghofran, AA, Borzouee, M, et al. Oral sildenafil to control pulmonary hypertension after congenital heart surgery. Asian Cardiovasc Thorac Ann 2007; 15: 113–117.CrossRefGoogle ScholarPubMed
Namachivayam, P, Theilen, U, Butt, WW, et al.. Sildenafil prevents rebound pulmonary hypertension after withdrawal of nitric oxide in children. Am J Respir Crit Care Med 2006; 174: 1042–1047.CrossRefGoogle ScholarPubMed
Baquero, H, Soliz, A, Neira, F, et al.. Oral sildenafil in infants with persistent pulmonary hypertension of the newborn: a pilot randomized blinded study. Pediatrics 2006; 117: 1077–1083.CrossRefGoogle ScholarPubMed