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

Abstract

Abstract Background Pulmonary arterial hypertension (PAH) is a syndrome characterized by marked remodeling of the pulmonary vasculature and leading to right heart failure and death. Selexipag, an oral prostacyclin IP receptor agonist, has been shown to decrease morbidity and mortality compared to patients treated with placebo. Purpose Our aim was to evaluate the efficacy and safety of Selexipag in patients with PAH in real-life. Methods The RAMPHA study was a multicenter, observational and retrospective trial of patients who had PAH and began taking Selexipag between 2017–2021. We analyzed baseline characteristics, risk profiles, clinical assessments that were used for risk stratification and events in follow-up time. Results 29 patients aged 48±14 were initially studied. 23 (79%) were women. Within the pulmonary hypertension-classification, 10 (34,5%) had PAH associated-congenital heart disease, 9 (31%) had idiopathic HAP, 7 (24,1%) had PAH associated with connective tissue disease, 1 had PAH associated to HIV and 2 heritable PAH. The time from PAH diagnoses to the beginning of Selexipag treatment was 54 months (IQR 89). 89,7% (26) were in treatment with doubled combination therapy with PDE5i+ARE; Sildenafil was the most widely used PDE5i and bosentan (37,9%) the most used ARE. No patients were under treatment with intravenous prostacyclin analogue, but 3 were with Treprostinil (1 of them subcutaneous and 2 inhaled) and 2 patients with iloprost. 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 93% of the patients. Only 15 patients had a right catheterization to get haemodynamic parameters before the treatment. At follow up, 11 patients (38%) improved functional class, only 1 patient got worst (p=0,001). 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 (924ng/l IQR 1209 vs 760ng/l IQR 1397). There were not changes in RV function in the echocardiographic parameters. Selexipag was well-tolerated, 86% of the patients experienced side effects, but none had to discountinue the treatment. The most common side effect was headache. The titration lasted 68 days (IQR 72) and 38% of the patients got maximum doses. At the medium-term follow-up of 52 months, the free-event survival (worsening of PAH that resulted in hospitalization; initiation of parenteral prostanoid therapy or death to PAH; or any cause) was 80% (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%. Funding Acknowledgement Type of funding sources: None.