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Pulmonary Vascular Disease |

Do Parameters of Cardiac Function Predict Long-term Outcomes in Patients With Pulmonary Arterial Hypertension? Data From SERAPHIN, a Randomized Controlled Study of Macitentan

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

Massachusetts General Hospital, Boston, MA, United States.


Chest. 2013;144(4_MeetingAbstracts):870B. doi:10.1378/chest.1701644
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Abstract

SESSION TITLE: DVT/PE/Pulmonary Hypertension Posters

SESSION TYPE: Original Investigation

PRESENTED ON: Wednesday, October 30, 2013 at 01:30 PM - 02:30 PM

PURPOSE: In the SERAPHIN trial (NCT00660179), macitentan significantly reduced the risk of morbidity and mortality (primary endpoint) in pulmonary arterial hypertension (PAH) patients. This analysis evaluated the predictive value of N-terminal pro-B natriuretic peptide (NT-pro-BNP), cardiac index (CI) and pulmonary vascular resistance (PVR) on this outcome.

METHODS: 742 PAH patients (≥12 years) were randomized to placebo, 3 mg or 10 mg macitentan, once daily. Hazard ratios (HR; 95% confidence intervals) were calculated to measure the association between the risk of morbidity and mortality and interquartile ranges (lowest=Q1 and highest=Q4) of NT-pro-BNP (n=495), CI (n=145) and PVR (n=145) at baseline, absolute values at Month 6, and change from baseline at Month 6. Univariate models and regression models unadjusted or adjusted for significant covariates were used, independently of treatment group. Analyses were performed in patients with available data for NT-pro-BNP, CI and PVR at Month 6, and from Month 6 up to end of treatment for morbidity and mortality.

RESULTS: Median baseline and Month 6 values for the placebo, 3 mg and 10 mg macitentan groups for NT-pro-BNP were 716 and 794 fmol/L (n=160), 841 and 759 fmol/L (n=165) and 807 and 707 fmol/L (n=170), respectively; for CI were 2.51 and 2.28 L/min/m2 (n=50), 2.23 and 2.70 L/min/m2 (n=47) and 2.56 and 3.06 L/min/m2 (n=48), respectively; and for PVR were 800 and 907 dyn.sec/cm5 (n=50), 785 and 600 dyn.sec/cm5 (n=47) and 789 and 536 dyn.sec/cm5 (n=48), respectively. The unadjusted HR for baseline NT-pro-BNP Q1 <517 fmol/L vs Q4 >1362 fmol/L was 6.25 (3.58–10.91), for CI Q1 <1.85 L/min/m2 vs Q4 >2.81 L/min/m2 was 2.62 (1.84–3.72) and for PVR Q1 <522 dyn.sec/cm5 vs Q4 >1314 dyn.sec/cm5 was 3.17 (2.14–4.70). Similarly, higher Month 6 absolute values for NT-pro-BNP and PVR, and lower Month 6 absolute values for CI were associated with significant increased risk in morbidity and mortality. Data were similar for both analyses when adjusted for covariates. There was no consistent association between change from baseline to Month 6 and risk of morbidity and mortality.

CONCLUSIONS: Higher NT-pro-BNP and PVR, and lower CI values at baseline and at Month 6 were significantly associated with a higher risk of morbidity and mortality, but changes from baseline were not.

CLINICAL IMPLICATIONS: Baseline and absolute values at Month 6 for NT-pro-BNP, CI and PVR are valuable cardiac function predictors of long-term outcome in PAH.

DISCLOSURE: Richard Channick; grant monies, Actelion. Marion Delcroix; consultant fee, speaker bureau, advisory committee, Actelion, GlaxoSmithKline, Pfizer, United Therapeutics, Bayer, grant monies, Actelion and GlaxoSmithKline. Nazzareno Galie; consultant fee, speaker bureau, advisory committee, grant monies Actelion, Pfizer, GlaxoSmithKline, Eli Lilly, Bayer. Hossein Ghofrani; consultant fee, speaker bureau, advisory committee, grant monies, Gilead, GlaxoSmithKline, Merck, Novartis, Pfizer, Bayer, Ergonex, Actelion. Pavel Jansa; consultant free, speaker bureau, advisory committee, United Therapeutics, AOP Orphan, Actelion, grant monies, Actelion. Franck-Olivier LeBrun: Employee, Actelion. Sanjay Mehta: grant monies, Heart & Stroke Foundation of Ontario/Canada, Canadian Institute of Health Research, Ontario Thoracic Society. Loic Perchenet: Employee, Actelion. Tomas Pulido: consultant fee, speaker bureau, advisory committee, Actelion, Pfizer, Eli Lilly, Bayer, grant monies Bayer, Actelion, United Therapeutics. B Sastry; consultant fee, speaker bureau, advisory committee, GlaxoSmithKline. Olivier Sitbon; consultant fee, speaker bureau, advisory committee, Actelion, GlaxoSmith Kline, Pfizer, Eli Lilly, United Therapeutics, grant monies, Actelion, GlaxoSmithKline, Pfizer, Eli Lilly, Bayer. Rogerio Souza; consultant fee, speaker bureau, advisory committee, Actelion, Eli Lilly, Bayer, GlaxoSmith Kline. Adam Torbicki; consultant fee, speaker bureau, advisory committee, Actelion, Eli Lilly, grant monies, Actelion, United Therapeutics, AOP Orphan Pharmaceutics, Pfizer, Bristol Myers Squibb, Sanofi Aventis. Lewis Rubin, consultant fee, speaker bureau, advisory committee, Actelion, Pfizer, United Therapeutics, Lung LLC, Gilead, Aires, GlaxoSmithKline, Bayer, GeNo. Gerald Simmonneau; consultant fee, speaker bureau, advisory committee, Actelion, GlaxoSmithKline, Eli Lilly, Pfizer, United Therapeutics, grant monies, Movartis, Actlion, GlaxoSmithKline, Eli Lilly, Pfizer.


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