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).

Actelion Pharmaceuticals Ltd Allschwil Switzerland

Assistance Publique Hôpitaux de Paris Service de Pneumologie Hôpital Bicêtre Le Kremlin Bicêtre France; Université Paris Sud Laboratoire d'Excellence en Recherche sur le Médicament et Innovation Thérapeutique Le Kremlin Bicêtre France; INSERM U 999 Centre Chirurgical Marie Lannelongue Le Plessis Robinson France

Cardiopulmonary Department Ignacio Chávez National Heart Institute Mexico City Mexico

Clinical Department of Cardiology and Angiology 1st Faculty of Medicine 2nd Medical Department Charles University Prague Czech Republic

Department of Cardiology CARE Hospitals Hyderabad India

Department of Experimental Diagnostic and Specialty Medicine DIMES Bologna University Hospital Bologna Italy

Department of Pneumology Gasthuisberg University Hospital Leuven Belgium

Department of Pulmonary Circulation and Thromboembolic Diseases Medical Center of Postgraduate Education ECZ Otwock Poland

Division of Pulmonary and Critical Care Medicine University of California San Diego Medical School San Diego California

Division of Respirology Department of Medicine London Health Sciences Centre Victoria Hospital Western University London Ontario Canada

Pulmonary and Critical Care Massachusetts General Hospital Boston Massachusetts

Pulmonary Department Heart Institute University of São Paulo Medical School São Paulo Brazil

University of Giessen and Marburg Lung Center Giessen Germany; Department of Medicine Imperial College London London United Kingdom

Citace poskytuje Crossref.org

Outcomes in Patients Receiving Treatment for Pulmonary Arterial Hypertension Associated With Repaired Congenital Heart Disease

Macitentan in Pulmonary Arterial Hypertension: A Focus on Combination Therapy in the SERAPHIN Trial

Zobrazit více v PubMed

ClinicalTrials.gov
NCT00660179