Macitentan for inoperable chronic thromboembolic pulmonary hypertension (CTEPH): results from the randomised controlled MERIT study

The efficacy and safety of the endothelin receptor antagonist macitentan in primary inoperable CTEPH, assessed by an independent adjudication committee, was evaluated in the randomised, double-blind MERIT study (NCT02021292). Patients in WHO functional class (FC) II–IV with pulmonary vascular resistance (PVR) ≥400 dyn∙sec/cm 5 and 6-minute walk distance (6MWD) of 150–450m were eligible. Treatment with phosphodiesterase type-5 inhibitors (PDE-5i) or oral/inhaled prostanoids was allowed for patients in WHO FC III–IV. Patients were randomised to placebo (n=40) or macitentan 10 mg (n=40) once daily for 24 weeks; 61% were receiving a PDE-5i or oral/inhaled prostanoids at baseline; 96% PDE-5i. Compared with placebo, the PVR (primary endpoint) and 6MWD significantly improved in the macitentan group. Macitentan-treated patients were less likely to experience WHO FC worsening vs placebo (Figure). PH-related disease progression occurred in 5.0% (macitentan) and 17.5% (placebo) of patients. Most common adverse events (macitentan vs placebo) were peripheral oedema (22.5% vs 10.0%) and decreased haemoglobin/anaemia (17.5% vs 2.5%). Five patients (placebo) prematurely discontinued treatment. Two patients (placebo) died. In the MERIT study, macitentan led to significant improvements in cardiopulmonary haemodynamics and clinical parameters in inoperable CTEPH patients and was well tolerated.