Introduction and objectives Macitentan, a novel dual endothelin receptor antagonist (ERA), significantly reduced morbidity and mortality in pulmonary arterial hypertension (PAH) patients in the SERAPHIN trial (NCT00660179), the first event-driven outcomes trial in PAH. A substudy in SERAPHIN investigated the effect of macitentan on patients' cardiac haemodynamics.

Methods 742 PAH patients were randomised to placebo, macitentan 3 mg, or macitentan 10 mg once-daily. Stable background PAH therapy, except injectable prostanoids and other ERAs, were allowed. At selected centres, patients underwent right heart catheterisation at randomisation and Month 6. Changes from baseline to Month 6 for mean right atrial pressure (mRAP), mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance (PVR), cardiac index (CI) and mixed venous oxygen saturation (SvO₂) were calculated for all patients and stratified in an exploratory analysis for background PAH therapy and baseline WHO functional class I/II vs III/IV. Median treatment effects (95% CL) between placebo and macitentan are reported.

Results 187 patients participated in the substudy (51% were treatment-naïve and 56% in WHO FC III/IV). Baseline median values for all patients on placebo (n = 68), macitentan 3 mg (n = 62) and 10 mg (n = 57) were: mRAP 7.0, 8.0, 7.0 mmHg; mPAP 52.0, 54.0, 52.3 mmHg; PVR 800, 785, 789 dyn·sec/cm⁵; CI 2.49, 2.23, 2.47 L/min/m²; and SvO₂ 66.0, 64.5, 66.5%, respectively. Overall, haemodynamic parameters improved at Month 6 with macitentan and worsened with placebo. Beneficial treatment effects with macitentan were statistically significant (P < 0.05) for PVR and CI for both subgroups, except for PVR in treatment naïve patients treated with macitentan 3mg (Table).

Conclusions Macitentan significantly improved cardio-pulmonary haemodynamics in PAH patients. Improvements in PVR and CI were consistent irrespective of background PAH therapy and baseline WHO FC.