Effect of macitentan on hospitalizations: results from the SERAPHIN trial.

Abstract

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).

• Authors: Richard N Channick, Marion Delcroix, Hossein-Ardeschir Ghofrani, Elke Hunsche, Pavel Jansa, Franck-Olivier Le Brun, Sanjay Mehta, Tomás Pulido, Lewis J Rubin, B K S Sastry, Gérald Simonneau, Olivier Sitbon, Rogério Souza, Adam Torbicki, Nazzareno Galiè
• Journal: JACC. Heart failure (JACC Heart Fail) Vol. 3 Issue 1 Pg. 1-8 (Jan 2015) ISSN: 2213-1787 [Electronic] United States
• PMID: 25457902 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Chemical References

• Endothelin A Receptor Antagonists
• Pyrimidines
• Sulfonamides
• macitentan

Topics

• Administration, Oral
• Adult
• Aged
• Disease Progression
• Dose-Response Relationship, Drug
• Double-Blind Method
• Endothelin A Receptor Antagonists (administration & dosage)
• Familial Primary Pulmonary Hypertension (drug therapy, physiopathology)
• Female
• Hospitalization (trends)
• Humans
• Male
• Middle Aged
• Pulmonary Wedge Pressure (drug effects)
• Pyrimidines (administration & dosage)
• Sulfonamides (administration & dosage)
• Treatment Outcome