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Background: Pulmonary arterial hypertension (PAH) is a common complication among patients with congenital heart disease (CHD). Despite advances in PAH treatment, evidence for the benefits of PAH therapies in CHD-PAH is limited. Objectives: This analysis aimed to evaluate outcomes in patients with repaired PAH-CHD receiving an approved PAH drug. Methods: This was a pooled analysis including CHD-PAH patients whose CHD was repaired ≥1 year prior from 3 randomized, placebo-controlled, event-driven studies: GRIPHON (NCT01106014), SERAPHIN (NCT00660179), and COMPASS-2 (NCT00303459). The primary endpoint was time to first confirmed morbidity/mortality (M/M) event. HRs with 95% CIs were determined with random effects models. Results: The analysis included 1,982 patients with PAH, 177 (8.9%) with CHD-PAH. In the overall PAH cohort, the mean age was 48 and 49 years in treatment and placebo groups; 80% and 77% were female. In the CHD-PAH cohort, the mean age was 41 and 39 years; 70% and 66% were female. Overall, ≥98% in each group were World Health Organization functional class II and III at baseline. There was a significant reduction in risk of M/M events vs placebo in the overall PAH and CHD-PAH cohorts: 37% reduction in the overall PAH cohort (HR: 0.63; 95% CI: 0.52-0.77) and 50% reduction in the CHD-PAH population (HR: 0.50; 95% CI: 0.26-0.94). Conclusions: Treatment with approved PAH drugs provided a similar reduction in M/M risk in patients with repaired CHD-PAH when compared with the overall PAH population. This pooled analysis provides important evidence to guide medical management in this patient population.

BACKGROUND: Age affects disease severity and patient outcomes in pulmonary arterial hypertension. This post-hoc analysis identified prognostic age groups and associated macitentan/selexipag treatment effects. METHODS: Randomized trials evaluated macitentan (SERAPHIN; NCT00660179) and selexipag (GRIPHON; NCT01106014) versus placebo (primary endpoint: time to morbidity/mortality [M/M]). This analysis defined age thresholds differentiating M/M risk in patients randomized to placebo (Cox regression determining treatment effect by age). RESULTS: Three age groups (< 35, 35–64, ≥ 65 years) showed good M/M risk discrimination (c-statistic 0.69, SERAPHIN; 0.66, GRIPHON). M/M risk was higher in placebo patients < 35 versus 35–64 years (SERAPHIN: hazard ratio [HR] 1.73, 95% confidence interval [CI] 1.10–2.72, p = 0.02; GRIPHON: HR 1.81, 95% CI 1.28–2.56, p < 0.001). M/M risk trended higher in patients ≥ 65 versus 35–64 years (SERAPHIN: HR 1.55, 95% CI 0.89–2.69, p = 0.12; GRIPHON (HR 1.08, 95% CI 0.75–1.55, p = 0.69). M/M risk was lower with macitentan/selexipag versus placebo: macitentan < 35 (HR 0.44, 95% CI 0.25–0.78; p = 0.005), 35–64 (HR 0.50, 95% CI 0.33–0.76; p < 0.001), ≥ 65 years (HR 0.69, 95% CI 0.30–1.58; p = 0.38); selexipag < 35 (HR 0.50, 95% CI 0.32–0.78; p = 0.002), 35–64 (HR 0.72, 95% CI 0.54–0.96; p = 0.03), ≥ 65 years (HR 0.55, 95% CI 0.33–0.91; p = 0.02). Adverse-event discontinuations were similar. CONCLUSIONS: The benefit (vs placebo) of macitentan/selexipag on reducing risk of M/M events was consistent across all ages, including the younger group where significant treatment effects were observed.

Background: Treprostinil, which is administered via continuous subcutaneous or intravenous infusion, is a medication applied in the treatment of pulmonary arterial hypertension (PAH). The dose of treprostinil is adjusted on an individual basis for each patient. A number of factors determine how well patients respond to treatment. Objectives: The aim of this study was to identify factors that may influence the clinical response to the dose of treprostinil at 3 months after the start of therapy. Methods: The factors influencing treatment response were analyzed in consecutive PAH patients who started receiving treprostinil treatment. The treatment efficacy was assessed as improvement in 6 min walk distance (6MWD) and WHO functional class (WHO FC), a reduction in N-terminal prohormone of brain natriuretic peptide (NTproBNP), and the percentage of patients achieving low-risk status after 12 months of treatment. Results: A total of 83 patients were included in this analysis. Classification of patients according to the tertiles of treprostinil dose achieved at 3 months after drug inclusion shows that after 12 months of follow-up, the median WHO FC in the highest dose group was lower than that in the intermediate dose group (WHO FC II vs. WHO FC III, p = 0.005), the median NTproBNP was lower (922 pg/mL, vs. 1686 pg/mL, p = 0.036) and 6MWD was longer (300 m vs. 510 m, p = 0.015). The French Noninvasive Criteria (NIFC) scale score was higher (2 vs. 0, p = 0.008), and the Reveal scale score was lower (5.0 vs. 8.5, p = 0.034). In the group of patients who exceeded a dose of 19.8 ng/kg/min within 3 months, an improvement in 6MWD was observed significantly more often after one year of therapy, and they were more likely to show an increase in NIFC scale scores after one year of therapy than the group of patients who received the lower dose (65% vs. 30%, p = 0.02). In the group of patients younger than 50 years of age, a statistically significant correlation was observed between the dose of treprostinil achieved after three months of treatment and the parameters assessed after 12 months of treatment, including WHO FC, 6MWD, and NIFC prognostic scale scores (all p < 0.05). Conclusions: The clinical effect of treatment is critically dependent on the rapid escalation of the treprostinil dose during the first three months of treatment.