OBJECTIVES: This study sought to evaluate the effect of macitentan on 
hospitalization of patients with symptomatic pulmonary arterial hypertension 
(PAH).
BACKGROUND: PAH is a progressive, life-threatening disease often requiring 
hospitalization.
METHODS: In the multicenter, double-blind, randomized, event-driven, phase III 
SERAPHIN (Study with an Endothelin Receptor Antagonist in Pulmonary arterial 
Hypertension to Improve cliNical outcome) trial, patients with symptomatic PAH 
were randomized (1:1:1) to receive placebo or 3 mg or 10 mg of macitentan. 
Effects of macitentan on the risk, rate, and number of hospital days for 
all-cause and PAH-related hospitalizations were compared with those for placebo. 
Risk and causes of hospitalizations unrelated to PAH were investigated.
RESULTS: Of 742 randomized patients, 250 received placebo, 250 received 3 mg of 
macitentan, and 242 received 10 mg of macitentan; the overall median duration of 
treatment was 115 weeks. Risk of all-cause hospitalization was reduced by 18.9% 
(p = 0.1208) and 32.3% (p = 0.0051) in the macitentan 3-mg and 10-mg arm, 
respectively. Rates of all-cause hospitalizations and numbers of hospital days 
were reduced by 20.5% (p = 0.0378) and 30.6% (p = 0.0278), respectively, with 3 
mg of macitentan and by 33.1% (p = 0.0005) and 31.0% (p = 0.0336), respectively, 
with 10 mg of macitentan. Risk of PAH-related hospitalizations were reduced by 
42.7% (p = 0.0015) and 51.6% (p < 0.0001) in the macitentan 3-mg and 10-mg arms, 
respectively. Rate of PAH-related hospitalizations and numbers of hospital days 
were reduced by 44.5% (p = 0.0004) and 53.3% (p = 0.0001), respectively, with 3 
mg of macitentan, and reduced by 49.8% (p < 0.0001) and 52.3% (p = 0.0003), 
respectively, with 10 mg of macitentan. Risk of non-PAH-related hospitalization 
was similar between treatment arms.
CONCLUSIONS: Macitentan 10 mg significantly reduced the risk and rate of 
all-cause hospitalization, which was driven by reductions in the risk and rate 
of PAH-related hospitalization. (Study of Macitentan [ACT-064992] on Morbidity 
and Mortality in Patients With Symptomatic Pulmonary Arterial Hypertension; 
NCT00660179).