A Meta-Analysis Of Randomized Controlled Trials In Pulmonary Arterialhypertension With Phosphodiesterase-5Inhibitors

Background:Various innovative pharmacologic strategies for the treatment of patients with pulmonary hypertension have been tested in recent years.The current drug therapy including prostanoids, endothelin receptor antagonist and PDE-5inhibitors. The phosphodiesterase-5(PDE5) inhibitor ofsildenafil has been reported to cause pulmonary vasodilation in patients with PAH. vardenafil and tadalafil are new PDE5inhibitors, recently being approved for the treatment of erectile dysfunction, there is a small number of clinical trials for the treatment on pulmonary hypertension. The safety and effectiveness of PDE-5inhibitors in PAH,there was no a system analysis.We performed a meta-analysis of all randomized controlled trials with drugs published in this condition.Methods:randomized controlled trials were searched in thePubMed> EMBASE> Cochrane Library CNKI、VIPdatabase from setting up to now. The primary analysis included only studies with a placebo comparator arm, the sensitivity analysis also included studies comparing two active treatment arms. the endpoint are6MWD, NYHA/WHO functional class, mortality, Haemodynamic parameters and adverse event.Results:Nine trials were included in the primary analysis(1143patients), Average durationof the trials was13.8weeks. The articles which evaluated by Cochrane assist recommended bias rist assessment method, all are low bias and English literature. Compared with placebo in the control group, treatment group can obviously increase in6MWD distance, the average of increase distance is41.49m,95%CI[31.46,51.51], P<0.001); Improvement of cardiac function in NYHA/WHO classification is obviously better than that of control group (RR=3.68,95%CI[1.42,9.58], P=0.008), and experimental group can significantly reduce the mortality (RR=0.35,95%CI[0.14,0.86], P=0.02);In Hemodynamics, compared with control group, pulmonary artery pressure average is feller(MD=-4.86mmHg,95%CI[-6.12,-3.60], P<0.001), in cardiac index improvement, the treatment group also showed its superiority, compared with the control group, the average cardiac index increased by0.39L/min/m, the difference was statistically significant (95%CI [0.25,0.54],P<0.001).In terms of safety, the treatment group vs the control group, with a lower incidence of acute adverse events(RR=1.02,95%CI [0.67,1.55], P=0.92).Conclusions:The treatment of PDE-5inhibitors in pulmonary hypertension, can improve the patient’s activity index, reduce mortality and improve cardiac function, incidence of adverse events do not increase.PAHpatients also has a better tolerability.