Effects of macitentan and selexipag across prognostic age groups in patients with pulmonary arterial hypertension

Richard Channick; Sarah Medrek; Marion Delcroix; Sean Gaine; Pavel Jansa; Irene Lang; Vallerie McLaughlin; Sanjay Mehta; Tomas Pulido; Bhagavatula Sastry; Rogerio Souza; Adam Torbicki; Carol Zhao; Paul Strachan; Peter Agron; Joseph Yen; Olivier Sitbon

doi:10.1016/j.jhlto.2024.100197

Effects of macitentan and selexipag across prognostic age groups in patients with pulmonary arterial hypertension

JHLT Open. 2025 Jan 16:7:100197. doi: 10.1016/j.jhlto.2024.100197. eCollection 2025 Feb.

Authors

Richard Channick¹, Sarah Medrek², Marion Delcroix³, Sean Gaine⁴, Pavel Jansa⁵, Irene Lang⁶, Vallerie McLaughlin⁷, Sanjay Mehta⁸, Tomas Pulido⁹, Bhagavatula Sastry¹⁰, Rogerio Souza¹¹, Adam Torbicki¹², Carol Zhao¹³, Paul Strachan¹³, Peter Agron¹⁴, Joseph Yen¹³, Olivier Sitbon¹⁵

Affiliations

¹ David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA.
² University of New Mexico, Albuquerque, NM.
³ University Hospitals of Leuven, Leuven, Belgium.
⁴ National Pulmonary Hypertension Unit, Mater Misericordiae University Hospital, Dublin, Ireland.
⁵ Second Department of Internal Medicine-Department of Cardiovascular Medicine, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic.
⁶ Department of Internal Medicine II, Cardiology and Center of Cardiovascular Medicine, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.
⁷ University of Michigan, Ann Arbor, MI.
⁸ Respirology Division, Department of Medicine, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada.
⁹ Clinical Research Department, National Heart Institute, Mexico City, Mexico.
¹⁰ CARE Hospitals, Hyderabad, India.
¹¹ InCor, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
¹² Centre of Postgraduate Medical Education, European Health Centre, ECZ-Otwock, Poland.
¹³ Actelion Pharmaceuticals US, Inc., (a Johnson & Johnson Company), Titusville, NJ.
¹⁴ Janssen Research and Development, LLC, Raritan, NJ.
¹⁵ Université Paris-Saclay, APHP, Hôpital Bicêtre, Le Kremlin-Bicêtre, France.

Abstract

Background: Age affects disease severity and patient outcomes in pulmonary arterial hypertension. This post-hoc analysis identified prognostic age groups and associated macitentan/selexipag treatment effects.

Methods: Randomized trials evaluated macitentan (SERAPHIN; NCT00660179) and selexipag (GRIPHON; NCT01106014) versus placebo (primary endpoint: time to morbidity/mortality [M/M]). This analysis defined age thresholds differentiating M/M risk in patients randomized to placebo (Cox regression determining treatment effect by age).

Results: Three age groups (< 35, 35-64, ≥ 65 years) showed good M/M risk discrimination (c-statistic 0.69, SERAPHIN; 0.66, GRIPHON). M/M risk was higher in placebo patients < 35 versus 35-64 years (SERAPHIN: hazard ratio [HR] 1.73, 95% confidence interval [CI] 1.10-2.72, p = 0.02; GRIPHON: HR 1.81, 95% CI 1.28-2.56, p < 0.001). M/M risk trended higher in patients ≥ 65 versus 35-64 years (SERAPHIN: HR 1.55, 95% CI 0.89-2.69, p = 0.12; GRIPHON (HR 1.08, 95% CI 0.75-1.55, p = 0.69). M/M risk was lower with macitentan/selexipag versus placebo: macitentan < 35 (HR 0.44, 95% CI 0.25-0.78; p = 0.005), 35-64 (HR 0.50, 95% CI 0.33-0.76; p < 0.001), ≥ 65 years (HR 0.69, 95% CI 0.30-1.58; p = 0.38); selexipag < 35 (HR 0.50, 95% CI 0.32-0.78; p = 0.002), 35-64 (HR 0.72, 95% CI 0.54-0.96; p = 0.03), ≥ 65 years (HR 0.55, 95% CI 0.33-0.91; p = 0.02). Adverse-event discontinuations were similar.

Conclusions: The benefit (vs placebo) of macitentan/selexipag on reducing risk of M/M events was consistent across all ages, including the younger group where significant treatment effects were observed.

Keywords: GRIPHON; Macitentan; Pulmonary arterial hypertension; SERAPHIN; Selexipag.