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
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This analysis defined age thresholds differentiating M/M risk in patients randomized to placebo (Cox regression determining treatment effect by age).</div></div><div><h3>RESULTS</h3><div>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, <em>p</em> = 0.02; GRIPHON: HR 1.81, 95% CI 1.28–2.56, <em>p</em> < 0.001). M/M risk trended higher in patients ≥ 65 versus 35–64 years (SERAPHIN: HR 1.55, 95% CI 0.89–2.69, <em>p</em> = 0.12; GRIPHON (HR 1.08, 95% CI 0.75–1.55, <em>p</em> = 0.69). M/M risk was lower with macitentan/selexipag versus placebo: macitentan < 35 (HR 0.44, 95% CI 0.25–0.78; <em>p</em> = 0.005), 35–64 (HR 0.50, 95% CI 0.33–0.76; <em>p</em> < 0.001), ≥ 65 years (HR 0.69, 95% CI 0.30–1.58; <em>p</em> = 0.38); selexipag < 35 (HR 0.50, 95% CI 0.32–0.78; <em>p</em> = 0.002), 35–64 (HR 0.72, 95% CI 0.54–0.96; <em>p</em> = 0.03), ≥ 65 years (HR 0.55, 95% CI 0.33–0.91; <em>p</em> = 0.02). Adverse-event discontinuations were similar.</div></div><div><h3>CONCLUSIONS</h3><div>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.</div></div>","PeriodicalId":100741,"journal":{"name":"JHLT Open","volume":"7 ","pages":"Article 100197"},"PeriodicalIF":0.0000,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Effects of macitentan and selexipag across prognostic age groups in patients with pulmonary arterial hypertension\",\"authors\":\"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\",\"doi\":\"10.1016/j.jhlto.2024.100197\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>BACKGROUND</h3><div>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.</div></div><div><h3>METHODS</h3><div>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).</div></div><div><h3>RESULTS</h3><div>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, <em>p</em> = 0.02; GRIPHON: HR 1.81, 95% CI 1.28–2.56, <em>p</em> < 0.001). M/M risk trended higher in patients ≥ 65 versus 35–64 years (SERAPHIN: HR 1.55, 95% CI 0.89–2.69, <em>p</em> = 0.12; GRIPHON (HR 1.08, 95% CI 0.75–1.55, <em>p</em> = 0.69). M/M risk was lower with macitentan/selexipag versus placebo: macitentan < 35 (HR 0.44, 95% CI 0.25–0.78; <em>p</em> = 0.005), 35–64 (HR 0.50, 95% CI 0.33–0.76; <em>p</em> < 0.001), ≥ 65 years (HR 0.69, 95% CI 0.30–1.58; <em>p</em> = 0.38); selexipag < 35 (HR 0.50, 95% CI 0.32–0.78; <em>p</em> = 0.002), 35–64 (HR 0.72, 95% CI 0.54–0.96; <em>p</em> = 0.03), ≥ 65 years (HR 0.55, 95% CI 0.33–0.91; <em>p</em> = 0.02). Adverse-event discontinuations were similar.</div></div><div><h3>CONCLUSIONS</h3><div>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.</div></div>\",\"PeriodicalId\":100741,\"journal\":{\"name\":\"JHLT Open\",\"volume\":\"7 \",\"pages\":\"Article 100197\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2025-02-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"JHLT Open\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2950133424001472\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"JHLT Open","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2950133424001472","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
摘要
背景：年龄影响肺动脉高压患者的疾病严重程度和预后。这项事后分析确定了预后年龄组和相关的马西坦/selexipag治疗效果。方法随机试验评价马西坦(SERAPHIN；NCT00660179)和selexipag (GRIPHON；NCT01106014)与安慰剂（主要终点：发病/死亡率的时间[M/M]）。该分析定义了随机分配到安慰剂组的患者区分M/M风险的年龄阈值（按年龄确定治疗效果的Cox回归）。结果三个年龄组(<；35岁、35 - 64岁、≥65岁)表现出良好的M/M风险区分(c统计量0.69，SERAPHIN；0.66, GRIPHON)。安慰剂组的M/M风险更高；35岁vs 35 - 64岁(SERAPHIN：风险比[HR] 1.73, 95%可信区间[CI] 1.10-2.72, p = 0.02；GRIPHON: HR 1.81, 95% CI 1.28-2.56, p <；0.001)。≥65岁患者的M/M风险高于35-64岁患者(SERAPHIN: HR 1.55, 95% CI 0.89-2.69, p = 0.12；GRIPHON（相对危险度1.08,95% CI 0.75-1.55, p = 0.69）。与安慰剂相比，马司坦/selexipag组的M/M风险更低：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 & lt;0.001)，≥65岁(HR 0.69, 95% CI 0.30-1.58；P = 0.38)；selexipag & lt;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岁(HR 0.55, 95% CI 0.33-0.91；P = 0.02)。不良事件停药的情况相似。结论：与安慰剂相比，马西坦/selexipag在降低M/M事件风险方面的益处在所有年龄段都是一致的，包括观察到显着治疗效果的年轻组。
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 (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.
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