Incident and prevalent cohorts with pulmonary arterial hypertension: insight from SERAPHIN.
In SERAPHIN, a long-term, randomised, controlled trial (NCT00660179) in pulmonary arterial hypertension (PAH), macitentan significantly reduced the risk of morbidity/mortality and PAH-related death/hospitalisation. We evaluated disease progression and the effect of macitentan in treatment-naïve incident and prevalent cohorts.Patients allocated to placebo, or macitentan 3 mg or 10 mg were classified by time from diagnosis to enrolment as incident (≤6 months; n=110) or prevalent (>6 months; n=157). The risk of morbidity/mortality and PAH-related death/hospitalisation was determined using Cox regression.The risk of morbidity/mortality (Kaplan-Meier estimates at month 12: 54.4% versus 26.7%; p=0.006) and PAH-related death/hospitalisation (Kaplan-Meier estimates at month 12: 47.3% versus 19.9%; p=0.006) were significantly higher for incident versus prevalent patients receiving placebo, respectively. There was no significant difference in the risk of all-cause death between incident and prevalent cohorts (p=0.587). Macitentan 10 mg significantly reduced the risk of morbidity/mortality and PAH-related death/hospitalisation versus placebo in incident and prevalent cohorts.Incident patients had a higher risk for PAH progression compared with prevalent patients but not a higher risk of death. Macitentan delayed disease progression in both incident and prevalent PAH patients.
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 gerald.simonneau@bct.aphp.fr.
Gérald
G
Simonneau
Pulmonary and Critical Care, Massachusetts General Hospital, Boston, MA, USA.
Richard N
RN
Channick
Department of Pneumology, Gasthuisberg University Hospital, Leuven, Belgium.
Marion
M
Delcroix
Department of Experimental, Diagnostic and Specialty Medicine (DIMES), Bologna University Hospital, Bologna, Italy.
Nazzareno
N
Galiè
University of Giessen and Marburg Lung Center, Giessen, Germany Member of the German Center of Lung Research (DZL), Giessen, Germany Department of Medicine, Imperial College London, London, UK.
Hossein-Ardeschir
HA
Ghofrani
Clinical Department of Cardiology and Angiology, 1st Faculty of Medicine, 2nd Medical Department, Charles University, Prague, Czech Republic.
Pavel
P
Jansa
Actelion Pharmaceuticals Ltd, Allschwil, Switzerland.
Franck-Olivier
FO
Le Brun
Division of Respirology, Department of Medicine, London Health Sciences Centre - Victoria Hospital, Western University, London, ON, Canada.
Sanjay
S
Mehta
Actelion Pharmaceuticals Ltd, Allschwil, Switzerland.
Loic
L
Perchenet
Cardiopulmonary Department, Ignacio Chávez National Heart Institute, Mexico City, Mexico.
Tomás
T
Pulido
Department of Cardiology, CARE Hospitals, Hyderabad, India.
B K S
BK
Sastry
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.
Olivier
O
Sitbon
Pulmonary Department, Heart Institute, University of São Paulo Medical School, São Paulo, Brazil.
Rogério
R
Souza
Department of Pulmonary Circulation and Thromboembolic Diseases, Center of Postgraduate Medical Education, ECZ-Otwock, Otwock, Poland.
Adam
A
Torbicki
Division of Pulmonary and Critical Care Medicine, University of California, San Diego Medical School, San Diego, CA, USA.
Lewis J
LJ
Rubin
D000328:Adult; D000368:Aged; D015331:Cohort Studies; D018450:Disease Progression; D004311:Double-Blind Method; D065128:Endothelin Receptor Antagonists / Q000627:therapeutic use*; D065627:Familial Primary Pulmonary Hypertension / Q000188:drug therapy* / Q000401:mortality; D005260:Female; D006760:Hospitalization; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy / Q000401:mortality; D015994:Incidence; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D016016:Proportional Hazards Models; D011743:Pyrimidines / Q000627:therapeutic use*; D013449:Sulfonamides / Q000627:therapeutic use*; D016896:Treatment Outcome
D065128:Endothelin Receptor Antagonists; D011743:Pyrimidines; D013449:Sulfonamides; C533860:macitentan