Triple combination therapy in pulmonary arterial hypertension

Pulmonary arterial hypertension is a severe disease characterized by increasing in pulmonary vascular resistance leading to right ventricular failure and death. Currently available drugs for treatment of PAH act on three different pathways responsible of the pathogenesis of this disease: the endothelin pathway, the nitric oxide pathway and the prostacyclin pathway. The purpose of our study was to reassess our experience on the use of drugs that interact on the pathobiological line of prostacyclin so we retrospectively included all patients, referred to our center from February 1995 to December 2021, who received therapy with i.v. Epoprostenol, s.c. Treprostinil or oral Selexipag. Firstly, we observed that patients treated with Epoprostenol were significantly more compromised at baseline when compared to the two other groups and evaluating the effects of the three different drugs, it emerged that patients treated with Epoprostenol had significantly greater improvements in respect to those treated with Treprostinil and Selexipag. In the second part of our analysis we assessed the effects of these drugs when used as third line strategy in order to limit many confounding factors that could influence demographic, clinical and hemodynamic characteristics of patient populations. The differences emerged in exercise capacity and baseline hemodynamics reflect the fact that in our clinical practice, we add Epoprostenol as third line therapy in more compromised patients, Treprostinil in intermediate situations and Selexipag in less impaired conditions. Comparing the effects of treatments between baseline and first follow-up we noticed smaller benefits with Selexipag when compared with intravenous and subcutaneous strategies but it’s important to weight baseline patient’s differences. Our analysis confirmed clinical and functional benefits for the use of both prostacyclin analogues and prostacyclin receptor agonists in terms of improved functional class, six-minute walking distance and cardiopulmonary hemodynamics.