Real-World Experience with Selexipag in Patients with Pulmonary Arterial Hypertension: Treatment Patterns and Outcomes across Baseline Risk Strata (SPHERE and EXPOSURE Studies)

Background: Treatment strategies for pulmonary arterial hypertension (PAH) depend on patients’ 1-year mortality risk; however, real-world practices and outcomes remain inadequately described. Objective: We aimed to investigate real-world experience with selexipag, an oral selective prostacyclin I2 receptor agonist used to treat PAH. Methods: This analysis of two large, prospective, observational studies: SPHERE (NCT03278002; USA; completed) and EXPOSURE (EUPAS19085; Europe and Canada; ongoing, data cutoff November 2021) included adults newly initiating selexipag with follow-up available. Results: Of 1366 selexipag users, 894 met eligibility criteria. At selexipag initiation, the median (Q1–Q3) age was 61 (48–70) years and the time since diagnosis was 2.7 (0.8–7.4) years. Most patients initiated selexipag within triple oral combination therapy (67%) with WHO-FC III symptoms (61%). During a median 10.8 (Q1–Q3: 3.3–18.6) months of selexipag exposure, 388 (43%) patients discontinued selexipag, mostly as a result of tolerability (n = 173, 19%) and death (n = 69, 8%). The median individualised dose was 800 μg twice-daily (n = 742). One-year mortality risk at selexipag initiation (assessable for 591 patients using a four-strata method): 22% were low-risk, 40% intermediate–low, 29% intermediate–high, and 9% high-risk. From low to high risk: 86%, 73%, 57% and 45% were free from all-cause hospitalisation at 1 year, and 1-year survival was 100%, 96%, 91%, and 59%, respectively. Conclusions: Despite current guidelines, over half of patients started selexipag almost 3 years after diagnosis, and 38% were already intermediate–high or high risk of 1-year mortality. Lower hospitalisation rates and better survival were observed for selexipag-treated patients in the low and intermediate–low risk groups versus higher risk groups.