Selexipag for pulmonary arterial hypertension in a wide range of adult congenital heart disease

Selexipag has been recognised as effective treatment for pulmonary arterial hypertension (PAH). However, evidence for its use in PAH associated with congenital heart disease (CHD) is limited to those with PAH after simple defect correction. We evaluated the response to selexipag in a wider range of PAH-CHD patients. Prospective observational cohort study recruiting adults with PAH-CHD who were initiated on selexipag treatment between 2017 and 2019 at five expert centres. Of 34 patients (age 46 ± 14.8 years, 67.6% female, 61.8% dual therapy, 32.4% complex shunt), 21 had Eisenmenger syndrome, 2 systemic-to-pulmonary shunt, and 11 PAH after defect correction. Majority of patients tolerated only low doses, with a median maintenance dose of 400 (IQR 200–800) μg twice daily. Ten (29.4%) patients, primarily with Eisenmenger syndrome, discontinued treatment due to unmanageable side effects. Median exposure to selexipag was 16.1 (IQR 6.0–25.8) months. Morbidity/mortality was high for patients with Eisenmenger syndrome, whereas patients with PAH after defect correction had an excellent event-free survival (Log-rank p = 0.04). Following current European guidelines, after 12 months of treatment, one patient with Eisenmenger syndrome and five patients with PAH after defect correction improved from ‘Intermediate’ to ‘Low’ risk, whereas two patients with Eisenmenger syndrome worsened in risk status (p = 0.028). Six-minute walk distance and N-terminal pro-brain natriuretic peptide levels remained stable, whereas improvement in World Health Organization functional class was observed in nine patients. These findings suggest that patients with PAH after defect correction may have better tolerability and more clinical benefit from selexipag than patients with Eisenmenger syndrome.