Introduction
Data on real-world clinical practice and outcomes of patients with pulmonary arterial hypertension (PAH) associated with congenital heart disease (CHD) are scarce. The OPUS/OrPHeUS studies enrolled patients with PAH newly initiating macitentan, including those with PAH associated with CHD (CHD-PAH).
Methods
OPUS was a prospective, United States, multicenter, long-term, observational drug registry (April 2014–June 2020). OrPHeUS was a retrospective, United States, multicenter medical chart review (October 2013–March 2017). The characteristics, treatment patterns, safety, and outcomes during macitentan treatment of patients with CHD-PAH and the subgroups Eisenmenger syndrome, left-to-right shunts and small/coincidental CHD were descriptively compared.
Results
The combined OPUS/OrPHeUS population included 272 (6.1%) patients with CHD-PAH (80 patients with Eisenmenger syndrome; 82 patients with left-to-right shunts and 92 patients with small/coincidental defects). Most patients across the CHD-PAH subgroups were in World Health Organization Functional Class II/III (82.9–94.6%). Macitentan was initiated as combination therapy in 65.0% of patients with CHD-PAH. During follow-up, 81.4% of patients experienced ≥ 1 adverse event (AE), the most common being dyspnea (23.5%), nausea (13.7%), dizziness (12.7%), headache (12.7%) and edema (10.8%). The 1- and 2-year Kaplan–Meier (95% confidence limits) estimates of patients with CHD-PAH being free from hospitalization were 64.5% (57.9, 70.4) and 49.3% (41.9, 56.3); for survival, the 1- and 2-year Kaplan–Meier estimates were 93.5% (89.3, 96.1) and 90.2% (84.9, 93.7).
Conclusions
Macitentan was used in clinical practice in patients with CHD-PAH and its subgroups, including as combination therapy in the majority of patients. Safety in this population was consistent with the known profile of macitentan.
Trial Registration
OPsumit
®
Users Registry (OPUS): NCT02126943; Opsumit
®
Historical Users cohort (OrPHeUS): NCT03197688; URL
www.clinicaltrials.gov
.
Plain Language Summary
Pulmonary arterial hypertension (PAH) is a deadly disease if left untreated and can develop in patients with congenital heart disease (CHD). PAH and CHD associated with PAH (CHD-PAH) are uncommon conditions. More information is needed on how these patients are treated in the clinic and the outcome of this trea...

Macitentan in Pulmonary Arterial Hypertension Due to Congenital Heart Disease (CHD-PAH): Real-World Evidence from the OPUS/OrPHeUS Studies

10.1007/s40119-024-00386-1