Effects of macitentan and selexipag across prognostic age groups in patients with pulmonary arterial hypertension
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 (GRIP...
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Elsevier
2025-02-01
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| Series: | JHLT Open |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2950133424001472 |
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| author | Richard Channick, MD Sarah Medrek, MD Marion Delcroix, MD Sean Gaine, MD Pavel Jansa, MD, PhD Irene Lang, MD Vallerie McLaughlin, MD Sanjay Mehta, MD Tomas Pulido, MD Bhagavatula Sastry, MD Rogerio Souza, MD, PhD Adam Torbicki, MD Carol Zhao, MS Paul Strachan, MD Peter Agron, PhD Joseph Yen, PhD Olivier Sitbon, MD, PhD |
| author_facet | Richard Channick, MD Sarah Medrek, MD Marion Delcroix, MD Sean Gaine, MD Pavel Jansa, MD, PhD Irene Lang, MD Vallerie McLaughlin, MD Sanjay Mehta, MD Tomas Pulido, MD Bhagavatula Sastry, MD Rogerio Souza, MD, PhD Adam Torbicki, MD Carol Zhao, MS Paul Strachan, MD Peter Agron, PhD Joseph Yen, PhD Olivier Sitbon, MD, PhD |
| author_sort | Richard Channick, MD |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-dc4f18334df94404a8a7b4d6e0695591 |
| institution | Kabale University |
| issn | 2950-1334 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
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| series | JHLT Open |
| spelling | doaj-art-dc4f18334df94404a8a7b4d6e06955912025-02-09T05:02:00ZengElsevierJHLT Open2950-13342025-02-017100197Effects of macitentan and selexipag across prognostic age groups in patients with pulmonary arterial hypertensionRichard Channick, MD0Sarah Medrek, MD1Marion Delcroix, MD2Sean Gaine, MD3Pavel Jansa, MD, PhD4Irene Lang, MD5Vallerie McLaughlin, MD6Sanjay Mehta, MD7Tomas Pulido, MD8Bhagavatula Sastry, MD9Rogerio Souza, MD, PhD10Adam Torbicki, MD11Carol Zhao, MS12Paul Strachan, MD13Peter Agron, PhD14Joseph Yen, PhD15Olivier Sitbon, MD, PhD16David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA; Reprint requests: Richard Channick, David Geffen School of Medicine at UCLA, 10833 Le Conte Ave, Los Angeles, CA 90095.University of New Mexico, Albuquerque, NMUniversity Hospitals of Leuven, Leuven, BelgiumNational Pulmonary Hypertension Unit, Mater Misericordiae University Hospital, Dublin, IrelandSecond Department of Internal Medicine–Department of Cardiovascular Medicine, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech RepublicDepartment of Internal Medicine II, Cardiology and Center of Cardiovascular Medicine, Medical University of Vienna, Währinger Gürtel 18–20, 1090 Vienna, AustriaUniversity of Michigan, Ann Arbor, MIRespirology Division, Department of Medicine, Schulich School of Medicine and Dentistry, Western University, London, ON, CanadaClinical Research Department, National Heart Institute, Mexico City, MexicoCARE Hospitals, Hyderabad, IndiaInCor, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, BrazilCentre of Postgraduate Medical Education, European Health Centre, ECZ-Otwock, PolandActelion Pharmaceuticals US, Inc., (a Johnson & Johnson Company), Titusville, NJActelion Pharmaceuticals US, Inc., (a Johnson & Johnson Company), Titusville, NJJanssen Research and Development, LLC, Raritan, NJActelion Pharmaceuticals US, Inc., (a Johnson & Johnson Company), Titusville, NJUniversité Paris-Saclay, APHP, Hôpital Bicêtre, Le Kremlin-Bicêtre, FranceBACKGROUND: 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.http://www.sciencedirect.com/science/article/pii/S2950133424001472Pulmonary arterial hypertensionSERAPHINGRIPHONSelexipagMacitentan |
| spellingShingle | Richard Channick, MD Sarah Medrek, MD Marion Delcroix, MD Sean Gaine, MD Pavel Jansa, MD, PhD Irene Lang, MD Vallerie McLaughlin, MD Sanjay Mehta, MD Tomas Pulido, MD Bhagavatula Sastry, MD Rogerio Souza, MD, PhD Adam Torbicki, MD Carol Zhao, MS Paul Strachan, MD Peter Agron, PhD Joseph Yen, PhD Olivier Sitbon, MD, PhD Effects of macitentan and selexipag across prognostic age groups in patients with pulmonary arterial hypertension JHLT Open Pulmonary arterial hypertension SERAPHIN GRIPHON Selexipag Macitentan |
| title | Effects of macitentan and selexipag across prognostic age groups in patients with pulmonary arterial hypertension |
| title_full | Effects of macitentan and selexipag across prognostic age groups in patients with pulmonary arterial hypertension |
| title_fullStr | Effects of macitentan and selexipag across prognostic age groups in patients with pulmonary arterial hypertension |
| title_full_unstemmed | Effects of macitentan and selexipag across prognostic age groups in patients with pulmonary arterial hypertension |
| title_short | Effects of macitentan and selexipag across prognostic age groups in patients with pulmonary arterial hypertension |
| title_sort | effects of macitentan and selexipag across prognostic age groups in patients with pulmonary arterial hypertension |
| topic | Pulmonary arterial hypertension SERAPHIN GRIPHON Selexipag Macitentan |
| url | http://www.sciencedirect.com/science/article/pii/S2950133424001472 |
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