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 .
Keywords: Congenital heart disease; Macitentan; Pulmonary arterial hypertension; Real-world evidence.
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 treatment. Macitentan is one medication for PAH. The OPUS (NCT02126943) and OrPHeUS (NCT03197688) studies collected information on patients with PAH living in the United States newly initiating macitentan between 2013 and 2020. In this work, we identified 272 patients with CHD-PAH. We found that 35% of patients with CHD-PAH received macitentan alone to treat their PAH, while 65% were treated with macitentan in addition to one or more other medications for PAH. In addition, we found that 81% experienced at least one side effect of macitentan, with the most common being shortness of breath, nausea, dizziness, headache, and edema. During the time of the study, 65% of patients remained hospitalization-free at 1 year and 49% at 2 years. After 1 year, 94% of patients were alive, and after 2 years, 90% of patients were alive. This analysis found that macitentan is used to treat patients with CHD-PAH in the United States, often alongside another medication for PAH. The side effects experienced by patients with CHD-PAH were similar to those experienced by other PAH patient populations and are known side effects of macitentan treatment.
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