Efficacy and safety of selexipag in real-life in patients with pulmonary arterial hypertension: early results of RAMPHA study

Abstract

Background: Pulmonary arterial hypertension (PAH) is a syndrome characterized by marked remodeling of the pulmonary vasculature and a progressive rise in the pulmonary vascular load, leading to right heart failure and death. The prostacyclin pathway is a therapeutic target used in this disease, and selexipag is an orally administered prostacyclin IP receptor agonist. Purpose: Our aim was to evaluate the efficacy and safety of Selexipag in patients with PAH in real-life. Methods: RAMPHA was a multicenter, observational and retrospective trial of patients who had PAH and began taking Selexipag between 2017 and 2021. We analyzed baseline characteristics, risk profiles and clinical assessments that were used for risk stratification and events in follow-up time. Results: 20 patients aged 50±13 were initially studied. 16 of them (80%) were women. Within the pulmonary hypertension classification, 6 (30%) of them had idiopathic HAP, 6 (30%) had PAH associated with connective tissue disease, 6 (30%) had PAH associated with congenital heart disease, 1 had PAH associated to HIV and 1 heritable PAH. The time from PAH diagnoses to the beginning of Selexipag treatment was 45 months (IQR 110). 85% of the patients (17) were in treatment with doubled combination therapy with PDE5i and ARE. No patients were under treatment with intravenous prostacyclin analogue, but 2 patients were with Treprostinil (1 subcutaneous and 1 inhaled). Most patients were categorized in intermediate-risk profile (figure 1), using the risk stratification strategy of ESC/ERS PH guidelines. In the approach of risk assessment before start with Selexipag, clinical, functional, exercise (with 6MWT) and echocardiographic variables were used in all the patients. Biochemical variables with NT-proBNP were used in 95% of the patients. Only 12 patients had a right catheterization to get haemodynamic parameters before the treatment. At follow up, 7 patients (35%) improved functional class, only 1 patient got worst. 3 patients improved risk profile in the exercise test and, in the others, a quantitative improvement was found. NT-proBNP levels were not significant better (631ng/l IQR 1179 versus. 443ng/l IQR 1441). There were not changes in RV function in the echocardiographic parameters. Selexipag was well-tolerated, 90% of the patients experienced side effects, but none had to discountinue the treatment. The most common side effect was headache. The titration lasted 64 days (IQR 40) and 45% of the patients got maximum doses. At the medium-term follow-up of 42 months, the free-event survival (worsening of pulmonary arterial hypertension that resulted in hospitalization; initiation of parenteral prostanoid therapy or death to PAH; or any cause) was 85% (Figure 2). Conclusion: Selexipag, added as triple combination therapy in patients with PAH intermediate risk, improved risk variables, was well tolerated and achieved a medium-long-term free-event survival greater than 80%.