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.

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 Bologna University Hospital Bologna Italy

Department of Pneumology Gasthuisberg University Hospital Leuven Belgium

Department of Pulmonary Circulation and Thromboembolic Diseases Center of Postgraduate Medical Education ECZ Otwock 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 Giessen Germany Member of the German Center of Lung Research Giessen Germany Department of Medicine Imperial College London London UK

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Galiè N, Manes A, Negro L, et al. . A meta-analysis of randomized controlled trials in pulmonary arterial hypertension. Eur Heart J 2009; 30: 394–403. PubMed PMC

Humbert M, Sitbon O, Yaici A, et al. . Survival in incident and prevalent cohorts of patients with pulmonary arterial hypertension. Eur Respir J 2010; 36: 549–555. PubMed

Humbert M, Sitbon O, Chaouat A, et al. . Survival in patients with idiopathic, familial, and anorexigen-associated pulmonary arterial hypertension in the modern management era. Circulation 2010; 122: 156–163. PubMed

D'Alonzo GE, Barst RJ, Ayres SM, et al. . Survival in patients with primary pulmonary hypertension. Results from a national prospective registry. Ann Intern Med 1991; 115: 343–349. PubMed

Miller DP, Farber HW, Poms AW, et al. . Five-year outcomes of the Registry To Evaluate Early And Long-Term Pulmonary Arterial Hypertension (PAH) Disease Management (REVEAL). Am J Respir Crit Care Med 2014; 183: A4741.

McGoon MD, Benza RL, Escribano-Subias P, et al. . Pulmonary arterial hypertension. J Am Coll Cardiol 2013; 62: D51–D59. PubMed

Miller DP, Gomberg-Maitland M, Humbert M. Survivor bias and risk assessment. Eur Respir J 2012; 40: 530–532. PubMed

Gatfield J, Mueller Grandjean C, Sasse T, et al. . Slow receptor dissociation kinetics differentiate macitentan from other endothelin receptor antagonists in pulmonary arterial smooth muscle cells. PLoS One 2012; 7: e47662. PubMed PMC

Gatfield J, Mueller Grandjean C, Bur D, et al. . Distinct ETA receptor binding mode of macitentan as determined by site directed mutagenesis. PLoS One 2014; 9: e107809. PubMed PMC

Iglarz M, Binkert C, Morrison K, et al. . Pharmacology of Macitentan, an Orally Active Tissue-Targeting Dual Endothelin Receptor Antagonist. J Pharmacol Exp Ther 2008; 327: 736–745. PubMed

Iglarz M, Bossu A, Wanner D, et al. . Comparison of pharmacological activity of macitentan and bosentan in preclinical models of systemic and pulmonary hypertension. Life Sci 2014; 118: 333–339. PubMed

Actelion Pharmaceuticals US, Inc. Opsumit (macitentan) prescribing information. https://opsumit.com/sites/opsumit/files/OPSUMIT-Full-Prescribing-Information.pdf Date last accessed: March, 2015. Date last updated: April, 2015.

Pulido T, Adzerikho I, Channick RN, et al. . Macitentan and morbidity and mortality in pulmonary arterial hypertension. N Engl J Med 2013; 369: 809–818. PubMed

Jansa P, Jarkovsky J, Al-Hiti H, et al. . Epidemiology and long-term survival of pulmonary arterial hypertension in the Czech Republic: a retrospective analysis of a nationwide registry. BMC Pulm Med 2014; 14: 45. PubMed PMC

Escribano-Subias P, Blanco I, López-Meseguer M, et al. . Survival in pulmonary hypertension in Spain: insights from the Spanish registry. Eur Respir J 2012; 40: 596–603. PubMed

Thenappan T, Shah SJ, Rich S, et al. . A USA-based registry for pulmonary arterial hypertension: 1982–2006. Eur Respir J 2007; 30: 1103–1110. PubMed

McLaughlin VV, Gaine SP, Howard LS, et al. . Treatment goals of pulmonary hypertension. J Am Coll Cardiol 2013; 62: D73–D81. PubMed

Gallagher DJ, Gaudet MM, Pal P, et al. . Germline BRCA mutations denote a clinicopathologic subset of prostate cancer. Clin Cancer Res 2010; 16: 2115–2121. PubMed PMC

Kelsey KT, Hankinson SE, Colditz GA, et al. . Glutathione S-transferase class mu deletion polymorphism and breast cancer: results from prevalent versus incident cases. Cancer Epidemiol Biomarkers Prev 1997; 6: 511–515. PubMed

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NCT00660179