Pulmonary arterial hypertension-related morbidity is prognostic for survival: Insights from the SERAPHIN and GRIPHON studies

Clinical and registry data suggest that pulmonary arterial hypertension (PAH) progression is indicative of poor prognosis. The prognostic relevance of PAH-related morbidity was evaluated based on observations from randomised controlled trials, SERAPHIN (N = 742) and GRIPHON (N = 1156). Both studies were double-blind, long-term, event-driven Phase III trials. In both, the primary endpoint was a composite of morbidity/mortality, prospectively defined and independently adjudicated. At three landmark time points, Months 3, 6 and 12, the risk of all-cause death until end of study was assessed according to whether patients had experienced a primary endpoint morbidity event up to the landmark. At Month 3, 720 SERAPHIN patients were at risk of death. Of those, 38 had experienced a morbidity event up to Month 3. Within the median follow-up period of 27 months, patients had > 3-fold increased risk of death compared with the 682 patients who had not experienced a morbidity event up to Month 3 (hazard ratio [HR] 3.39 [95% confidence interval (CI) 1.94, 5.92]). Similar observations were made in the GRIPHON population: 1127 patients were at risk of death at Month 3; 62 patients had experienced a morbidity event up to Month 3 and had > 4-fold increased risk of death within the next 20 months (median follow up) compared with the 1065 patients who had not (HR 4.48 [95% CI 2.98, 6.73]). In both studies, analyses at Months 6 and 12 yielded similar findings. These results confirm the prognostic relevance of PAH-related morbidity and the importance of its prevention in patients with PAH.