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Macitentan Improves Cardiopulmonary Hemodynamics (HD) in Patients with Pulmonary Arterial Hypertension (PAH): Results from the randomized SERAPHIN Trial

David Badesch


Richard Channick


Nazzareno Galie


L Perchenet

Lewis Rubin


Gerald Simonneau

Olivier Sitbon

Adam Torbicki


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Conference: 2014 International PHA Conference and Scientific Sessions

Release Date: 06.21.2014

Presentation Type: Abstracts

File Download: 2014 Conference Abstract - David Badesch

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Background: In the SERAPHIN trial, macitentan significantly reduced the time from treatment initiation to first occurrence of a composite endpoint of death, atrial septostomy, lung transplantation, initiation of intravenous or subcutaneous prostanoid, or PAH worsening. A substudy of the trial assessed the effect of macitentan on cardiopulmonary HD.

Methods: In SERAPHIN (NCT00660179), 742 PAH patients were randomized 1:1:1 to placebo, macitentan 3mg, or macitentan 10mg qd. A subset of patients (n=187) underwent right heart catheterization at randomization and after 6 months of treatment to measure mean right atrial pressure (mRAP), mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance (PVR), cardiac index (CI), and mixed venous oxygen saturation (SvO2). The treatment effect of macitentan versus placebo was explored in all patients in the substudy and in subgroups categorized according to the presence of background PAH therapy or WHO functional class (FC) at baseline.

Results: Mean baseline HD for the placebo (n=68), macitentan 3mg (n=62), and macitentan 10mg (n=57) arms were: mRAP 7.9, 8.9, 8.3 mmHg; mPAP 53.4, 52.9, 53.6 mmHg; PVR 900, 934, 924 dyn•sec/cm5; CI 2.5, 2.4, 2.6 L/min/m2; and SvO2 65.3, 63.3, 64.8%, respectively. All HD parameters improved after 6 months of treatment with macitentan and worsened with placebo. Both doses of macitentan significantly improved mPAP, CI, and PVR (p<0.05) versus placebo and these beneficial effects were consistent for CI and PVR irrespective of the presence of background PAH therapy or WHO FC at baseline (Table). The safety profile of patients was consistent with the overall SERAPHIN population.

Conclusions: In SERAPHIN, macitentan improved cardiopulmonary HD in PAH patients irrespective of the presence of background PAH therapy or WHO FC at baseline.

Placebo-corrected treatment effect of macitentan on PVR and CI at Month 6

  PVR (% change from baseline*)  CI (L/min/m2)    
Patients Macitentan 3mg Macitentan 10mg  Macitentan 3mg Macitentan 10mg
All (n = 187) −33.6 (−42.2, −23.8)
−38.5 (−47.8, 27.5) 0.7 (0.4, 0.9) 0.6 (0.3, 0.9)
Without background PAH therapy (n=95) −27.2** (−44.1, −5.4) −38.7 (−53.3, −19.5) 0.6 (0.2, 1.0) 0.6 (0.1, 1.2)
With background PAH therapy (n=92) −37.4 (−46.6, −26.7) −36.9 (−48.5, −22.7) 0.7 (0.4, 1.0) 0.6 (0.2, 1.0)

WHO FC I/II (n=82)

−40.9 (−52.8, −25.9) −44.7 (−57.0, −29.0) 0.7 (0.3, 1.1) 0.7 (0.2, 1.2)

WHO FC III/IV (n=105)

−27.9 (−39.7, −13.8) −32.6 (−46.0, −15.8)

0.7 (0.4, 1.0)

0.6 (0.2, 1.0)
  1. Mean (95% confidence interval)
  2. * (Ratio of geometric means - 1) x 100
  3. p <0.05 for all (Wilcoxon test) except**

Type: Clinical Science