A network meta-analysis for safety of endothelin receptor antagonists in pulmonary arterial hypertension

Background: Currently, direct comparative safety between endothelin receptor antagonists (ERAs) in pulmonary arterial hypertension (PAH) is limited. Thus, a systematic review with network analysis was conducted. Methods: An electronic search was performed for randomized controlled trials (RCTs) that reported the interested safety data (abnormal liver function, peripheral edema, and anemia) of ERAs in PAH. Risk ratios (RRs) with their confidence intervals (CIs) and the surface under the cumulative ranking curve (SUCRA) were calculated using a network analysis. Results: Ten RCTs involving 2,288 patients were included. Compared with placebo, bosentan (RR, 2.93; 95% CI, 1.78-4.84) significantly increased the risk of abnormal liver function, ambrisentan (RR, 1.62; 95% CI, 1.23-2.13) significantly increased the risk of peripheral edema, and macitentan (RR, 3.42; 95% CI, 1.65-7.07) significantly increased the risk of anemia. SUCRA analysis suggested that bosentan 125 mg twice daily had the highest risk of abnormal liver function; ambrisentan 10 mg once daily had the highest risk of peripheral edema; macitentan 10 mg once daily had the highest risk of anemia. Conclusions: Abnormal liver function (bosentan), peripheral edema (ambrisentan), and anemia (macitentan) were the safety indicators of ERAs in patients with PAH. Different monitoring parameters should be considered for individual ERA.