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Pulmonary Vascular Disease |

Association Between WHO Functional Class and Long-term Prognosis in Patients With Pulmonary Arterial Hypertension: Data From SERAPHIN, A Randomized Controlled Study of Macitentan

Rogério Souza, 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; Adam Torbicki, MD; Lewis Rubin, MD; Gérald Simonneau, MD
Author and Funding Information

University of São Paulo Medical School, São Paulo, Brazil


Chest. 2013;144(4_MeetingAbstracts):879A. doi:10.1378/chest.1701714
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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 (NCT00660179), macitentan significantly reduced the risk of morbidity and mortality in patients with pulmonary arterial hypertension (PAH). This analysis explored the association of short-term changes in WHO functional class (FC) with the long-term outcome of death due to PAH or hospitalization for PAH (DHPAH).

METHODS: 742 PAH patients (≥12 years) were randomized to placebo, 3 mg or 10 mg macitentan, once daily. Hazard ratios (HR; 95% confidence interval), both unadjusted and adjusted for significant baseline covariates, were calculated using Cox proportional hazard models, to measure the association between DHPAH and A) patients in FC II at baseline who, at Month 6, remained in FC II versus those who worsened to FC III/IV or improved to FC I; B) patients in FC III at baseline who, at Month 6, remained in FC III versus those who worsened to FC IV or improved to FC I/II. These analyses were performed independently of treatment in patients with available data for FC at Month 6 and from Month 6 up to end of treatment for DHPAH.

RESULTS: At baseline, 387 patients were in FC II and 337 in FC III. The proportion of DHPAH events in patients in FC II at baseline who, at Month 6, remained in FC II was 15.8%, worsened to FC III/IV was 29.2% and improved to FC I was 14.3%; HR for the risk of DHPAH events in patients who worsened or improved from FC II at baseline against unchanged were 3.71 (1.67-8.25; P=0.001) and 0.85 (0.34-2.15; P=0.74). The proportion of DHPAH events in patients in FC III at baseline who, at Month 6, remained in FC III was 30.8%, worsened to FC IV was 37.5% and improved to FC I/II was 23.3%; HR for the risk of DHPAH events in patients who worsened or improved from FC III at baseline against unchanged were 5.16 (1.57-17.0; P=0.007) and 0.66 (0.39-1.11; P=0.116). Data were similar when analyses were adjusted for significant baseline covariates.

CONCLUSIONS: Deterioration in FC over a 6-month period was significantly associated with a higher risk of DHPAH. For patients in FC III at baseline, improvement to FC I/II over 6 months was associated with a non-significant reduction in risk of DHPAH compared with those who remained in FC III.

CLINICAL IMPLICATIONS: Short-term worsening in FC is clearly associated with a worse long-term prognosis, while improving to FC II over the short term, might be associated with improved long-term prognosis.

DISCLOSURE: 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 Richard Channick: Grant monies (from industry related sources): Actelion 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.: Gilead, Consultant fee, speaker bureau, advisory committee, etc.: Actelion, 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: Consultant fee, speaker bureau, advisory committee, etc.: Actelion, Consultant fee, speaker bureau, advisory committee, etc.: Pfizer, 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): Bayer, Grant monies (from industry related sources): United Therapuetics B. Sastry: Consultant fee, speaker bureau, advisory committee, etc.: GlaxoSmithKline 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 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 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

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


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