Clinical and Hemodynamic Effects of Endothelin Receptor Antagonists in Patients With Heart Failure: A Meta-Analysis of Randomized Controlled Trials

The clinical benefit of endothelin receptor antagonists (ERA) for the management of heart failure (HF) remains controversial. To examine this question, we performed a meta-analysis of randomized controlled trials (RCTs) to investigate the clinical and hemodynamic effects of ERA in HF patients.We searched the PubMed, Medline, Embase, and Cochrane Library from inception to March 20, 2016 to identify the pertinent studies. Risk ratio (RR) and weighted mean difference (WMD) were calculated using a fixed or random effect model.A total of 15 RCTs with 3,624 HF patients were included. Compared with control groups, ERA might not improve the mortality (RR 1.12, 95%CI 0.81 to 1.54, P = 0.51) or incidence of worsening HF or cardiovascular events (WHF/ CVE) (RR 1.06, 95%CI 0.94 to 1.19, P = 0.35) in HF patients. Subgroup analysis also suggested that neither nonselective nor selective ERAs had an impact on mortality and WHF/CVE. However, the hemodynamic variables of HF patients, including cardiac index (WMD 0.32, 95%CI 0.22 to 0.43, P < 0.01), pulmonary capillary wedge pressure (WMD -3.10, 95%CI -3.99 to -2.20, P < 0.01), mean pulmonary arterial pressure (WMD -4.42, 95%CI -5.50 to -3.33, P < 0.01), systemic vascular resistance (WMD -276.35, 95%CI -399.62 to -153.09, P < 0.01), and pulmonary vascular resistance (WMD -69.42, 95%CI -105.33 to -33.52, P < 0.01) were significantly improved by ERA.In conclusion, this meta-analysis suggests that ERA therapy could effectively improve cardiac output and pulmonary and systemic hemodynamics, but with less benefit to the clinical outcomes of HF patients.