Switching to riociguat versus maintenance therapy with phosphodiesterase-5 inhibitors in patients with pulmonary arterial hypertension (REPLACE): a multicentre, open-label, randomised controlled trial

里奥西瓜特 医学 他达拉非 cGMP特异性磷酸二酯酶5型 西地那非 肺动脉高压 内科学 内皮素受体拮抗剂 心脏病学 慢性血栓栓塞性肺高压 内皮素受体 受体
作者
Marius M. Hoeper,Hikmet Al‐Hiti,Raymond L. Benza,Sung‐A Chang,Paul A. Corris,J. Simon R. Gibbs,Ekkehard Grünig,P Jansa,James R. Klinger,David Langleben,Vallerie V. McLaughlin,G. Meyer,Jaquelina Sonoe Ota Arakaki,Andrew J. Peacock,Tomás Pulido,Stephan Rosenkranz,Carmine Dario Vizza,Anton Vonk Noordegraaf,R.J. White,Mikyung Chang,Frank Kleinjung,Christian Meier,Karen Paraschin,Hossein A. Ghofrani,Gérald Simonneau,Horst Olschewski,Marion Delcroix,Marina Andrade‐Lima,R de Amorim Corrêac,F Figueiredo Campos,Jaquelina O. Arakaki,G. Meyer,Rogério Souza,David Langleben,Hikmet Al‐Hiti,P Jansa,Søren Mellemkjær,Fabrice Bauer,David Montani,Gérald Simonneau,Daniel Drömann,Hossein A. Ghofrani,Ekkehard Grünig,Michael Halank,Matthias Held,Marius M. Hoeper,Hans Klose,Nikolaus Kneidinger,Hanno Leuchte,Christian Opitz,Stephan Rosenkranz,Heinrike Wilkens,Hubert Wirtz,Haralampos Karvounis,Georgia Pitsiou,Stylianos E. Orfanos,Michael D’Alto,Stefano Ghio,CD Vizza,Patrizio Vitulo,T. Nakayama,Hisataka Maki,Shunsuke Tatebe,Manuel Ibarra,Tomás Pulido,Arie P.J. van Dijk,Anton Vonk Noordegraaf,Tomasz Roleder,G. Castro,MJ Loureiro,Susana Robalo-Martins,Joan Albert Barberà,M. Lázaro,GM Perez-Penate,Antonio Román,Ching‐Chang Cheng,C-H Hsu,H-H Hsu,Erhan Atahan,Nesrin Moğulkoç,NG Okumus,Zeynep Pınar Önen,Chang Hj,Sung‐A Chang,Jin Sun Lee,Hyung‐Kwan Kim,JG Coghlan,PA Corris,Colin Church,Robin Condliffe,J. Simon R. Gibbs,AJ Peacock,Stephen J. Wort,Roblee P. Allen,Samuel A. Allen,Rana Awdish,RL Benza,Shilpa A. DeSouza,Jeremy Feldman,Shilpa Johri,JR Klinger,Daniel Layish,John McConnell,VV McLaughlin,Christina Migliore,Franck Rahaghi,Franz Rischard,Ivan M. Robbins,Lewis Satterwhite,Trushil Shah,Roxana Sulica,R.J. White
出处
期刊:The Lancet Respiratory Medicine [Elsevier]
卷期号:9 (6): 573-584 被引量:112
标识
DOI:10.1016/s2213-2600(20)30532-4
摘要

Riociguat and phosphodiesterase-5 inhibitors (PDE5i), approved for the treatment of pulmonary arterial hypertension (PAH), act on the same pathway via different mechanisms. Riociguat might be an alternative option for patients with PAH who do not respond sufficiently to treatment with PDE5i, but comparisons of the potential benefits of riociguat and PDE5i in these patients are needed. The aim of this trial was to assess the effects of switching to riociguat from PDE5i therapy versus continued PDE5i therapy in patients with PAH at intermediate risk of 1-year mortality.Riociguat rEplacing PDE5i therapy evaLuated Against Continued PDE5i thErapy (REPLACE) was an open-label, randomised controlled trial in 81 hospital-based pulmonary hypertension centres in 22 countries. The study enrolled patients aged 18-75 years with symptomatic PAH at intermediate risk of 1-year mortality (based on the European Society for Cardiology-European Respiratory Society guideline thresholds for WHO functional class and 6-min walk distance [6MWD]) who were receiving treatment with a PDE5i with or without an endothelin receptor antagonist for at least 6 weeks before randomisation. Patients were excluded if they had been previously treated with riociguat, had used prostacyclin analogues or prostacyclin receptor agonists within 30 days before randomisation, had clinically significant restrictive or obstructive parenchymal lung disease, or had left heart disease. Patients were randomly assigned (1:1) to remain on PDE5i treatment (oral sildenafil [≥60 mg per day] or oral tadalafil [20-40 mg per day]; the PDE5i group) or to switch to oral riociguat (up to 2·5 mg three times per day; the riociguat group), using an interactive voice and web response system, stratified by cause of PAH. The primary endpoint was clinical improvement by week 24, defined as an absence of clinical worsening and prespecified improvements in at least two of three variables (6MWD, WHO functional class, and N-terminal prohormone of brain natriuretic peptide), analysed using last observation carried forward in all randomly assigned patients with observed values at baseline and week 24 who received at least one dose of study medication (the full analysis set). Secondary endpoints included clinical worsening events. The trial has been completed and is registered with ClinicalTrials.gov, NCT02891850.Between Jan 11, 2017, and July 31, 2019, 293 patients were screened, of which 226 patients were randomly assigned to the riociguat group (n=111) or to the PDE5i group (n=115). 211 patients completed the study and 14 patients discontinued (seven in each group). One patient assigned to the PDE5i group did not receive treatment, so 225 patients were included in the safety analysis, and one further patient in the PDE5i group had missing components of the composite primary endpoint at baseline, so 224 patients were included in the full analysis set. The primary endpoint was met by 45 (41%) of 111 patients in the riociguat group and 23 (20%) of 113 patients in the PDE5i group; odds ratio [OR] 2·78 (95% CI 1·53-5·06; p=0·0007). Clinical worsening events occurred in one (1%) of 111 patients in the riociguat group (hospitalisation due to worsening PAH) and 10 (9%) of 114 patients in the PDE5i group (hospitalisation due to worsening PAH [n=9]; disease progression [n=1]; OR 0·10 [0·01-0·73]; p=0·0047). The most frequently occurring adverse events were hypotension (15 [14%]), headache (14 [13%]), and dyspepsia (10 [9%]) in the riociguat group, and headache (eight [7%]), cough (seven [6%]), and upper respiratory tract infection (seven [6%]) in the PDE5i group. Serious adverse events were reported in eight (7%) of 111 patients in the riociguat group and 19 (17%) of 114 patients in the PDE5i group. During the study, four patients died in the PDE5i group, one of them during the safety follow-up period.Switching to riociguat from PDE5i treatment, both of which act via the nitric oxide-soluble guanylate cyclase-cyclic guanosine monophosphate pathway, could be a strategic option for treatment escalation in patients with PAH at intermediate risk of 1-year mortality.Bayer AG, Merck Sharp & Dohme.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
大幅提高文件上传限制,最高150M (2024-4-1)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
聪明的鹤完成签到 ,获得积分10
3秒前
HappyFlight9898完成签到,获得积分10
5秒前
livra1058完成签到,获得积分10
6秒前
GraceWu完成签到,获得积分10
7秒前
lwtsy完成签到,获得积分10
8秒前
简单幸福完成签到 ,获得积分10
8秒前
MEMSforever发布了新的文献求助10
10秒前
烤全鱼呢关注了科研通微信公众号
11秒前
lpx43完成签到,获得积分10
13秒前
吴大宝完成签到,获得积分10
16秒前
18秒前
跳跃的访琴完成签到 ,获得积分10
18秒前
wind完成签到 ,获得积分10
24秒前
烽烽烽发布了新的文献求助10
25秒前
要努力坚持啊完成签到,获得积分10
26秒前
言悦完成签到,获得积分10
26秒前
小可完成签到 ,获得积分10
29秒前
Minjalee完成签到,获得积分10
29秒前
lily完成签到,获得积分10
31秒前
GJL发布了新的文献求助10
32秒前
沧海一粟米完成签到 ,获得积分10
33秒前
luoziwuhui完成签到,获得积分10
35秒前
Gavin完成签到,获得积分10
40秒前
风衣拖地完成签到 ,获得积分10
42秒前
June完成签到 ,获得积分10
43秒前
匆匆赶路人完成签到 ,获得积分10
47秒前
认真的白莲完成签到,获得积分10
49秒前
Yuuuu完成签到 ,获得积分10
50秒前
万元帅完成签到 ,获得积分10
51秒前
科研小南瓜完成签到 ,获得积分10
51秒前
娟儿完成签到 ,获得积分10
51秒前
啦啦啦啦完成签到 ,获得积分10
53秒前
PandaC完成签到,获得积分10
55秒前
GJL完成签到,获得积分20
56秒前
57秒前
共享精神应助谦虚采纳,获得10
1分钟前
风中梦蕊完成签到 ,获得积分10
1分钟前
852应助YC采纳,获得10
1分钟前
llbeyond应助科研通管家采纳,获得30
1分钟前
和平使命应助科研通管家采纳,获得10
1分钟前
高分求助中
좌파는 어떻게 좌파가 됐나:한국 급진노동운동의 형성과 궤적 2500
Sustainability in Tides Chemistry 1500
TM 5-855-1(Fundamentals of protective design for conventional weapons) 1000
Cognitive linguistics critical concepts in linguistics 800
Threaded Harmony: A Sustainable Approach to Fashion 799
Livre et militantisme : La Cité éditeur 1958-1967 500
氟盐冷却高温堆非能动余热排出性能及安全分析研究 500
热门求助领域 (近24小时)
化学 医学 生物 材料科学 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 基因 遗传学 催化作用 物理化学 免疫学 量子力学 细胞生物学
热门帖子
关注 科研通微信公众号,转发送积分 3052675
求助须知:如何正确求助?哪些是违规求助? 2709898
关于积分的说明 7418335
捐赠科研通 2354494
什么是DOI,文献DOI怎么找? 1246139
科研通“疑难数据库(出版商)”最低求助积分说明 605951
版权声明 595921