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Pulmonary Vascular Disease |

Effect of Macitentan on Long-term Outcomes in Patients With Pulmonary Arterial Hypertension (PAH): Subanalysis of SERAPHIN Comparing Incident and Prevalent Patient Populations Not Treated With Background PAH-Specific Therapy

Gérald Simonneau, MD; Richard Channick, MD; Marion Delcroix, MD; Nazzareno Galiè, MD; Hossein Ghofrani, MD; Pavel Jansa, MD; Franck - Olivier Le Brun; Sanjay Mehta, MD; Loic Perchenet, PhD; Tomas Pulido, MD; B. Sastry, MD; Olivier Sitbon, MD; Rogério Souza, MD; Adam Torbicki, MD; Lewis Rubin, MD
Author and Funding Information

Hôpital Universitaire de Bicêtre, Le Kremlin-Bicêtre, France


Chest. 2013;144(4_MeetingAbstracts):876A. doi:10.1378/chest.1701395
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Abstract

SESSION TITLE: Pulmonary Hypertension

SESSION TYPE: Original Investigation Slide

PRESENTED ON: Monday, October 28, 2013 at 01:45 PM - 03:15 PM

PURPOSE: In SERAPHIN, a randomized, controlled trial (NCT00660179) in pulmonary arterial hypertension (PAH), macitentan significantly reduced the risk of morbidity and mortality (primary endpoint) and death due to PAH or hospitalization for PAH (DHPAH; secondary endpoint). This subanalysis examined the effects of macitentan on long-term outcomes in incident and prevalent patients not receiving background PAH-specific therapy (treatment-naïve patients).

METHODS: 742 PAH patients (≥12 years) were randomized to placebo, 3 mg or 10 mg macitentan, once daily. According to the delay between PAH diagnosis and inclusion into the study, treatment-naïve patients were classified as incident (≤6 months) or prevalent (>6 months). Unadjusted hazard ratios (HR; 95% confidence intervals) were calculated using Cox regression models to determine the treatment effect of macitentan on morbidity and mortality and DHPAH.

RESULTS: Of 265 treatment-naïve patients, 108 were incident and 157 were prevalent patients; median time from PAH diagnosis to study inclusion was 50 and 834 days, respectively. At baseline for incident and prevalent patients, median 6-minute walk distance was 357 and 370 m, cardiac index was 2.37 and 2.45 L/min/m2 and pulmonary vascular resistance was 780 and 733 dyn.sec/cm5 respectively. A morbidity/mortality event occurred in 63.9, 40.0 and 38.2% of incident patients and 42.4, 28.9 and 24.5% of prevalent patients on placebo, macitentan 3 mg and 10 mg, respectively. For morbidity and mortality, the HR for macitentan 3 mg and 10 mg, respectively, were 0.38 (0.20-0.73) and 0.40 (0.20-0.79) in incident patients and 0.60 (0.31-1.17) and 0.47 (0.24-0.91) in prevalent patients. For DHPAH, the HR for macitentan 3 mg and 10 mg, respectively, for incident patients were 0.45 (0.23-0.91) and 0.22 (0.09-0.57) and for prevalent patients were 0.49 (0.20-1.18) and 0.38 (0.16-0.92).

CONCLUSIONS: Incident and prevalent PAH patients had similar baseline disease severity, yet the natural history of incident patients (placebo arm) show a higher risk of morbidity and mortality. Despite their poor prognosis, macitentan significantly reduced the risk of morbidity and mortality in both incident and prevalent PAH patients.

CLINICAL IMPLICATIONS: Macitentan is an effective first-line therapy for improving long-term outcomes in both newly diagnosed and prevalent PAH patients.

DISCLOSURE: Gérald Simonneau: Consultant fee, speaker bureau, advisory committee, etc.: Actelion, Consultant fee, speaker bureau, advisory committee, etc.: GlaxoSmithKline, Consultant fee, speaker bureau, advisory committee, etc.: Eli Lilly, Consultant fee, speaker bureau, advisory committee, etc.: Pfizer, Consultant fee, speaker bureau, advisory committee, etc.: United Therapeutics, Consultant fee, speaker bureau, advisory committee, etc.: Novartis, Grant monies (from industry related sources): Actelion, Grant monies (from industry related sources): GlaxoSmithKline, Grant monies (from industry related sources): Eli Lilly, Grant monies (from industry related sources): Pfizer Marion Delcroix: Consultant fee, speaker bureau, advisory committee, etc.: Actelion, Consultant fee, speaker bureau, advisory committee, etc.: GlaxoSmithKline, Consultant fee, speaker bureau, advisory committee, etc.: Pfizer, Consultant fee, speaker bureau, advisory committee, etc.: United Therapeutics, Consultant fee, speaker bureau, advisory committee, etc.: Bayer, Grant monies (from industry related sources): Actelion, Grant monies (from industry related sources): GlaxoSmithKline Nazzareno Galiè: Consultant fee, speaker bureau, advisory committee, etc.: Actelion, Consultant fee, speaker bureau, advisory committee, etc.: Pfizer, Consultant fee, speaker bureau, advisory committee, etc.: GlaxoSmithKline, Consultant fee, speaker bureau, advisory committee, etc.: Eli Lilly, Consultant fee, speaker bureau, advisory committee, etc.: Bayer, Grant monies (from industry related sources): Actelion, Grant monies (from industry related sources): Pfizer, Grant monies (from industry related sources): GlaxoSmithKline, Grant monies (from industry related sources): Eli Lilly, Grant monies (from industry related sources): Bayer Hossein Ghofrani: Consultant fee, speaker bureau, advisory committee, etc.: Actelion, Consultant fee, speaker bureau, advisory committee, etc.: Gilead, Consultant fee, speaker bureau, advisory committee, etc.: GlaxoSmithKline, Consultant fee, speaker bureau, advisory committee, etc.: Merck, Consultant fee, speaker bureau, advisory committee, etc.: Novartis, Consultant fee, speaker bureau, advisory committee, etc.: Pfizer, Consultant fee, speaker bureau, advisory committee, etc.: Bayer, Consultant fee, speaker bureau, advisory committee, etc.: Ergonex, Grant monies (from industry related sources): Actelion, Grant monies (from industry related sources): Bayer, Grant monies (from industry related sources): Ergonex, Grant monies (from industry related sources): Pfizer Pavel Jansa: Consultant fee, speaker bureau, advisory committee, etc.: United Therapeutics, Consultant fee, speaker bureau, advisory committee, etc.: AOP Orphan, Consultant fee, speaker bureau, advisory committee, etc.: Actelion, Grant monies (from industry related sources): Actelion Franck - Olivier Le Brun: Employee: Actelion, Shareholder: Actelion Sanjay Mehta: Grant monies (from industry related sources): Heart & Stroke Foundation of Ontario/Canada (HSFO/C), Grant monies (from industry related sources): Canadian Institute of Health Research / CIHR, Grant monies (from industry related sources): Ontario Thoracic Society (OTS) Loic Perchenet: Employee: Actelion Pharmaceuticals Ltd, Shareholder: Actelion Pharmaceuticals Ltd Tomas Pulido: Grant monies (from industry related sources): National Heart Institute, Consultant fee, speaker bureau, advisory committee, etc.: Actelion B. Sastry: Consultant fee, speaker bureau, advisory committee, etc.: Actelion, Consultant fee, speaker bureau, advisory committee, etc.: GlaxoSmithKine Olivier Sitbon: Consultant fee, speaker bureau, advisory committee, etc.: Actelion, Consultant fee, speaker bureau, advisory committee, etc.: GlaxoSmithKline, Consultant fee, speaker bureau, advisory committee, etc.: Pfizer, Consultant fee, speaker bureau, advisory committee, etc.: Eli Lilly, Consultant fee, speaker bureau, advisory committee, etc.: United Therapeutics, Grant monies (from industry related sources): Actelion, Grant monies (from industry related sources): GlaxoSmithKline, Grant monies (from industry related sources): Pfizer, Grant monies (from industry related sources): Eli Lilly, Grant monies (from industry related sources): Bayer Rogério Souza: Consultant fee, speaker bureau, advisory committee, etc.: Actelion, Consultant fee, speaker bureau, advisory committee, etc.: Ely Lilly, Consultant fee, speaker bureau, advisory committee, etc.: Bayer, Consultant fee, speaker bureau, advisory committee, etc.: GlaxoSmithKline Adam Torbicki: Consultant fee, speaker bureau, advisory committee, etc.: Actelion, Consultant fee, speaker bureau, advisory committee, etc.: Ely Lilly, Grant monies (from industry related sources): Bayer, Grant monies (from industry related sources): Actelion , Grant monies (from industry related sources): United Therapeutics, Grant monies (from industry related sources): AOP Orphan Pharmaceutics, Grant monies (from industry related sources): Pfizer, Grant monies (from industry related sources): Bristol Myers Squibb, Grant monies (from industry related sources): Sanofi Aventis Lewis Rubin: Consultant fee, speaker bureau, advisory committee, etc.: Actelion, Consultant fee, speaker bureau, advisory committee, etc.: Pfizer, Consultant fee, speaker bureau, advisory committee, etc.: United Therapeutics, Consultant fee, speaker bureau, advisory committee, etc.: Lung LLC, Consultant fee, speaker bureau, advisory committee, etc.: Gilead, Consultant fee, speaker bureau, advisory committee, etc.: Aires, Consultant fee, speaker bureau, advisory committee, etc.: GlaxoSmithKline, Consultant fee, speaker bureau, advisory committee, etc.: Bayer, Consultant fee, speaker bureau, advisory committee, etc.: GeNo The following authors have nothing to disclose: Richard Channick

Macitentan is currently under regulatory review as a treatment for pulmonary arterial hypertension


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