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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.

Patients with portal hypertension may develop pulmonary hypertension. The economic implications of these comorbidities have not been systematically assessed. We compared healthcare resource utilization and costs in the United States between patients with co-existing portal hypertension and pulmonary hypertension (pulmonary hypertension cohort) and a matched cohort of portal hypertension patients without pulmonary hypertension (control cohort). In this retrospective analysis, adult pulmonary hypertension and control patients were identified from the Optum® Clinformatics® Data Mart database between 1 July 2014 and 30 June 2018. All patients had ≥2 claims with diagnosis codes for portal hypertension; pulmonary hypertension patients had ≥2 claims with diagnosis codes for pulmonary hypertension; controls could not have pulmonary hypertension diagnoses or any claims for pulmonary arterial hypertension-specific medications. Controls were matched to pulmonary hypertension patients by age, sex, Charlson comorbidity index score, and liver diseases. We assessed 12-month healthcare resource utilization and costs. Each cohort included 146 patients. During follow-up, pulmonary hypertension cohort patients were more likely than controls to experience a hospitalization (51% vs. 32%, P = 0.0014) and an emergency room visit (55% vs. 41%, P = 0.026). The average annual total cost was higher in pulmonary hypertension patients than for matched controls ($119,912 vs. $81,839, P