P5462Evaluation of macitentan in patients with Eisenmenger syndrome: results from the randomised controlled MAESTRO study

Introduction: Eisenmenger syndrome (ES) describes congenital heart disease-associated severe pulmonary hypertension accompanied by right-to-left intravascular shunting. The global randomised, double-blind, phase 3 MAESTRO study (NCT01743001) evaluated efficacy and safety of macitentan in patients with ES. Methods: ES patients aged ≥12 yrs and in WHO functional class (FC) II–IV were randomised 1:1 to placebo or macitentan 10mg once daily and treated for 16 weeks. Patients with complex cardiac defects were eligible. The primary endpoint in the main study was change from baseline to Week 16 in 6 minute walk distance (6MWD) and in a haemodynamic substudy, pulmonary vascular resistance (PVRi). Results: 226 patients (macitentan n=114; placebo n=112) including 20 with Down Syndrome were enrolled. At baseline, median (min, max) time from ES diagnosis was 4.7 (0, 59) yrs, 60% were in FC II, and 27% were receiving phosphodiesterase type-5 inhibitors. At Week 16, the mean change from baseline in 6MWD was 18.3m and 19.7m and WHO FC improved in 8.8% and 14.3% of patients in the macitentan and placebo groups respectively (Table). NT-proBNP levels decreased with macitentan vs placebo (Table). In the haemodynamic substudy (n=39), PVRi decreased and 6MWD increased with macitentan vs placebo (Table). The most common adverse events (AEs) with macitentan vs placebo were headache (11.4 vs 4.5%) and upper respiratory tract infection (9.6 vs 6.3%). Five patients (3 macitentan; 2 placebo) prematurely discontinued treatment. One death due to respiratory failure was reported in the macitentan group; this was considered unrelated to the drug.