Early selexipag initiation and long-term outcomes: insights from randomised controlled trials in pulmonary arterial hypertension

被引：12

作者：

Coghlan, J. Gerry ^{[1
]}

Gaine, Sean ^{[2
]}

Channick, Richard ^{[3
]}

Chin, Kelly M. ^{[4
]}

du Roure, Camille ^{[5
]}

Gibbs, J. Simon R. ^{[6
]}

Hoeper, Marius M. ^{[7
,8
]}

Lang, Irene M. ^{[9
]}

Mathai, Stephen C. ^{[10
]}

McLaughlin, Vallerie V. ^{[11
]}

Mitchell, Lada ^{[12
]}

Simonneau, Gerald ^{[13
]}

Sitbon, Olivier ^{[13
]}

Tapson, Victor F. ^{[14
]}

Galie, Nazzareno ^{[15
,16
]}

机构：

[1] Royal Free Hosp, London, England

[2] Mater Misericordiae Univ Hosp, Dublin, Ireland

[3] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA

[4] UT Southwestern Med Ctr, Dallas, TX USA

[5] Actelion Pharmaceut Ltd, Janssen Pharmaceut Co Johnson & Johnson, Global Med Affairs, Allschwil, Switzerland

[6] Imperial Coll London, Natl Heart & Lung Inst, London, England

[7] Hannover Med Sch, Dept Resp Med, Hannover, Germany

[8] German Ctr Lung Res, Hannover, Germany

[9] Med Univ Vienna, Div Cardiol, Vienna, Austria

[10] Johns Hopkins Univ, Sch Med, Baltimore, MD USA

[11] Univ Michigan, Ann Arbor, MI 48109 USA

[12] Actelion Pharmaceut Ltd, Janssen Pharmaceut Co Johnson & Johnson, Stat & Decis Sci Med Affairs & Established Prod, Allschwil, Switzerland

[13] Univ Paris Sud, Hop Bicetre, Le Kremlin Bicetre, France

[14] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA

[15] Univ Bologna, Alma Mater Studiorum, Bologna, Italy

[16] IRCCS, S Orsola Univ Hosp, Bologna, Italy

来源：

ERJ OPEN RESEARCH | 2023年 / 9卷 / 01期

关键词：

TIME; THERAPY;

D O I：

10.1183/23120541.00456-2022

中图分类号：

R56 [呼吸系及胸部疾病];

学科分类号：

摘要：

Further understanding of when to initiate therapies in pulmonary arterial hypertension (PAH) is important to improve long-term outcomes. Post hoc analyses of GRIPHON (NCT01106014) and exploratory analyses of TRITON (NCT02558231) suggested benefit of early selexipag initiation on long-term outcomes, despite no additional benefit versus initial double combination on haemodynamic and functional parameters in TRITON. Post hoc analyses investigated the effect of early selexipag initiation on disease progression and survival in a large, pooled PAH cohort. Data from newly diagnosed (<= 6 months) PAH patients from GRIPHON and TRITON were pooled. Patients on active therapy with selexipag ( pooled selexipag group) were compared with those on control therapy with placebo ( pooled control group). Disease progression end-points were defined as per the individual studies. Hazard ratios (HR) and 95% CI for time to first disease progression event up to end of double-blind treatment (selexipag/placebo) +7 days and time to all-cause death up to end of study were estimated using Cox regression models. The pooled dataset comprised 649 patients, with 44% on double background therapy. Selexipag reduced the risk of disease progression by 52% versus control (HR: 0.48; 95% CI: 0.35-0.66). HR for risk of all-cause death was 0.70 (95% CI: 0.46-1.10) for the pooled selexipag versus control group. Sensitivity analyses accounting for the impact of PAH background therapy showed consistent results, confirming the appropriateness of data pooling. These post hoc, pooled analyses build on previous insights, further supporting selexipag use within 6 months of diagnosis, including as part of triple therapy, to delay disease progression.

引用

页数：11

共 19 条

[1] Statistical methodologies to pool across multiple intervention studies [J].