The Efficacy And Safety Of Pulmonary Vasodilators In Patients With Fontan Circulation: A Meta-analysis Of Randomized Controlled Trials

Background:Previously no meta-analysis has evaluated the efficacy and safety of targeted therapies of pulmonary arterial hypertension,also called pulmonary vasodilators,in Fontan physiology.Recent relative trials have obtained conflicting results regarding improvements in peak oxygen consumption;the relatively small number of patients in each study may be a limiting factor.Methods:Relevant clinical studies were identified by searching the PubMed,Embase,and Cochrane Library databases and Clinicaltrial.gov.Pooled outcomes were determined to assess the efficacy and safety of pulmonary vasodilators in Fontan patients.Results:Nine randomized controlled studies involving 381 patients with Fontan circulation were included.Pulmonary vasodilator therapy led to significant improvement（MD=-0.39,95%CI:[-0.72,-0.05]）in the New York Heart Association（NYHA）functional class.The 6-minute walking distance（6MWD）was significantly increased by 134m（95%CI:[86.07,181.94]）,and the peak VO2 was also significantly improved(MD=1.42ml·（kg·min）^-1,95%CI:[0.21,2.63]).Additionally,the mean pulmonary artery pressure（mPAP）was significantly reduced（MD=-2.25 mmHg,95%CI:[-3.00,-1.50]）.No significant change was found in mortality.Four studies reported no side effects and good drug tolerance,and two studies reported mild adverse effects.Conclusion:The present meta-analysis indicated that pulmonary vasodilators（primarily the PDE-5 inhibitor and endothelin-1 receptor antagonist）significantly improved the hemodynamics of Fontan patients,reduced the NYHA functional class and increased the 6MWD.The peak oxygen consumption was also improved.No significant change was observed in mortality.Overall,the pulmonary vasodilators were well tolerated.This finding needs to be confirmed in future studies.