Macitentan improves risk categorization for liver transplant mortality in patients with portopulmonary hypertension: A PORTICO study post‐hoc analysis
2020
Portopulmonary hypertension (PoPH) is pulmonary arterial hypertension (PAH) associated with portal hypertension, usually caused by liver cirrhosis. Prognosis is poor for patients with PoPH and liver transplant (LT) can be life-saving; however, pre- and post-transplant outcomes depend on pre-LT cardiopulmonary hemodynamics. The recently-completed PORTICO study evaluated the effects of macitentan, an endothelin receptor antagonist, in PoPH patients and was the first randomized controlled trial of a PAH therapy specifically conducted in this patient population. In PORTICO, 85 participants were randomized to receive either macitentan (n=43) or placebo (n=42). The study showed that macitentan significantly improved pulmonary vascular resistance (PVR) and mean pulmonary arterial pressure (mPAP) as compared with placebo, was generally well tolerated and did not lead to further adverse liver conditions. Here we report a post-hoc analysis of the PORTICO study, evaluating whether changes in PVR and mPAP could improve risk categorization for LT mortality. Based on hemodynamic criteria and changes achieved after 12 weeks, treatment with macitentan improved patients' risk category for both LT perioperative mortality (odds ratio: 4.9; 95% confidence interval: 1.6, 17.7) and waitlist mortality (odds ratio: 10.5; 95% confidence interval: 2.4, 66.8). In conclusion, macitentan treatment could potentially decrease the risk of LT-related death in PoPH patients; however, further research is required to establish if these changes translate into improvements in survival in a real-world setting.
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