AIMS: The effect of macitentan on haemodynamic parameters and NT-proBNP levels was evaluated in pulmonary arterial hypertension (PAH) patients in the SERAPHIN study. Association between these parameters and disease progression, assessed by the primary endpoint (time to first morbidity/mortality event), was explored. METHODS AND RESULTS: Of the 742 randomized patients, 187 with right heart catheterization at baseline and month 6 participated in a haemodynamic sub-study. Prespecified endpoints included change from baseline to month 6 in cardiac index (CI), right atrial pressure (RAP), mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance (PVR), mixed-venous oxygen saturation, and NT-proBNP. Exploratory analyses examined associations between CI, RAP, and NT-proBNP and disease progression using the Kaplan-Meier method and Cox regression models. Macitentan improved CI, RAP, mPAP, PVR and NT-proBNP vs. placebo at month 6. Absolute levels of CI, RAP and NT-proBNP at baseline and month 6, but not their changes, were associated with morbidity/mortality events. Patients with CI > 2.5 L/min/m2, RAP < 8 mmHg, or NT-proBNP < 750 fmol/ml at month 6 had a lower risk of morbidity/mortality than those not meeting these thresholds (HR 0.49, 95% CL 0.28-0.86; HR 0.72, 95% CL 0.42-1.22; and HR 0.22, 95% CL 0.15-0.33, respectively). CONCLUSIONS: For all treatment groups, baseline and month 6 values of CI, RAP, and NT-proBNP, but not their changes, were associated with morbidity/mortality events, confirming their relevance in predicting disease progression in patients with PAH. By improving those parameters, macitentan increased the likelihood of reaching threshold values associated with lower risk of morbidity/mortality.

Actelion Pharmaceuticals Ltd Allschwil Switzerland

Assistance Publique Hôpitaux de Paris Service de Pneumologie Hôpital Bicêtre Université Paris Sud Laboratoire d'Excellence en Recherche sur le Médicament et Innovation Thérapeutique and INSERM U 999 Le Kremlin Bicêtre 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 via Massarenti 9 Bologna 40138 Italy

Department of Pneumology Gasthuisberg University Hospital Leuven Belgium

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

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

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

Pulmonary and Critical Care Massachusetts General Hospital Boston MA USA

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

University of Giessen and Marburg Lung Center and Department of Medicine Imperial College London London UK

Eur Heart J. 2017 Apr 14;38(15):1156-1158. doi: 10.1093/eurheartj/ehx123. PubMed

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