Xinzhi Hu, Zongmuyu Zhang, Caiyan Liu, Mingli Li, Yiyang Liu, Anqi Cheng, Qiuyu Yu, Haoyao Guo, Yinxi Zou, Li Zhou, Hebo Wang, Bo Song, Yong You, Jian Xia, Jingfen Zhang, Zhibing Ai, Qinjian Sun, Ju Han, Jing Liu, Baoquan Lu, Qiwen Deng, Guanzeng Li, Peng-Fei Wang, Xiangqing Li, Yi An, Bo Wu, Zhongrui Yan, Yining Wang, Wei-Hai Xu
{"title":"PCSK9抑制剂与他汀类药物治疗颅内动脉狭窄(PISTIAS):多中心随机对照试验的原理与设计。","authors":"Xinzhi Hu, Zongmuyu Zhang, Caiyan Liu, Mingli Li, Yiyang Liu, Anqi Cheng, Qiuyu Yu, Haoyao Guo, Yinxi Zou, Li Zhou, Hebo Wang, Bo Song, Yong You, Jian Xia, Jingfen Zhang, Zhibing Ai, Qinjian Sun, Ju Han, Jing Liu, Baoquan Lu, Qiwen Deng, Guanzeng Li, Peng-Fei Wang, Xiangqing Li, Yi An, Bo Wu, Zhongrui Yan, Yining Wang, Wei-Hai Xu","doi":"10.1177/17474930241270447","DOIUrl":null,"url":null,"abstract":"<p><strong>Rationale: </strong>Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors enable an additional 54-75% reduction in low-density lipoprotein cholesterol (LDL-C) in statin-treated patients, demonstrating plaque regression in coronary artery disease. However, the impact of achieving an extremely low level of LDL-C with PCSK9 inhibitors (e.g. Evolocumab) on symptomatic intracranial atherosclerosis remains unexplored.</p><p><strong>Aim and hypothesis: </strong>To determine whether combining Evolocumab and statins achieves a more significant symptomatic intracranial plaque regression than statin therapy alone.</p><p><strong>Sample size estimates: </strong>With a sample size of 1000 subjects, a two-sided α of 0.05, and 20% lost to follow-up, the study will have 83.3% power to detect the difference in intracranial plaque burden.</p><p><strong>Methods and design: </strong>This is an investigator-initiated multicenter, randomized, open-label, outcome assessor-blinded trial, evaluating the impact of combining Evolocumab and statins on intracranial plaque burden assessed by high-resolution magnetic resonance imaging at baseline in patients undergoing a clinically indicated acute stroke or transient ischemic attack due to intracranial artery stenosis, and after 24 weeks of treatment. Subjects (n = 1000) were randomized 1:1 into two groups to receive either Evolocumab 140 mg every 2 weeks with statin therapy or statin therapy alone.</p><p><strong>Study outcomes: </strong>The primary endpoint is the change in intracranial plaque burden assessed by high-resolution magnetic resonance imaging, performed at baseline and at the end of the 24-week treatment period.</p><p><strong>Discussion: </strong>This trial will explore whether more significant intracranial plaque regression is achievable with the treatment of combining Evolocumab and statins, providing information about efficacy and safety data.</p><p><strong>Trial registration number: </strong>ChiCTR2300068868; https://www.chictr.org.cn/.</p>","PeriodicalId":14442,"journal":{"name":"International Journal of Stroke","volume":null,"pages":null},"PeriodicalIF":6.3000,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"PCSK9 Inhibitor with Statin Therapy for Intracranial Artery Stenosis ( PISTIAS): Rationale and design of a multicenter randomized controlled trial.\",\"authors\":\"Xinzhi Hu, Zongmuyu Zhang, Caiyan Liu, Mingli Li, Yiyang Liu, Anqi Cheng, Qiuyu Yu, Haoyao Guo, Yinxi Zou, Li Zhou, Hebo Wang, Bo Song, Yong You, Jian Xia, Jingfen Zhang, Zhibing Ai, Qinjian Sun, Ju Han, Jing Liu, Baoquan Lu, Qiwen Deng, Guanzeng Li, Peng-Fei Wang, Xiangqing Li, Yi An, Bo Wu, Zhongrui Yan, Yining Wang, Wei-Hai Xu\",\"doi\":\"10.1177/17474930241270447\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Rationale: </strong>Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors enable an additional 54-75% reduction in low-density lipoprotein cholesterol (LDL-C) in statin-treated patients, demonstrating plaque regression in coronary artery disease. However, the impact of achieving an extremely low level of LDL-C with PCSK9 inhibitors (e.g. Evolocumab) on symptomatic intracranial atherosclerosis remains unexplored.</p><p><strong>Aim and hypothesis: </strong>To determine whether combining Evolocumab and statins achieves a more significant symptomatic intracranial plaque regression than statin therapy alone.</p><p><strong>Sample size estimates: </strong>With a sample size of 1000 subjects, a two-sided α of 0.05, and 20% lost to follow-up, the study will have 83.3% power to detect the difference in intracranial plaque burden.</p><p><strong>Methods and design: </strong>This is an investigator-initiated multicenter, randomized, open-label, outcome assessor-blinded trial, evaluating the impact of combining Evolocumab and statins on intracranial plaque burden assessed by high-resolution magnetic resonance imaging at baseline in patients undergoing a clinically indicated acute stroke or transient ischemic attack due to intracranial artery stenosis, and after 24 weeks of treatment. Subjects (n = 1000) were randomized 1:1 into two groups to receive either Evolocumab 140 mg every 2 weeks with statin therapy or statin therapy alone.</p><p><strong>Study outcomes: </strong>The primary endpoint is the change in intracranial plaque burden assessed by high-resolution magnetic resonance imaging, performed at baseline and at the end of the 24-week treatment period.</p><p><strong>Discussion: </strong>This trial will explore whether more significant intracranial plaque regression is achievable with the treatment of combining Evolocumab and statins, providing information about efficacy and safety data.</p><p><strong>Trial registration number: </strong>ChiCTR2300068868; https://www.chictr.org.cn/.</p>\",\"PeriodicalId\":14442,\"journal\":{\"name\":\"International Journal of Stroke\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":6.3000,\"publicationDate\":\"2024-10-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"International Journal of Stroke\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1177/17474930241270447\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/8/15 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Stroke","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1177/17474930241270447","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/8/15 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
PCSK9 Inhibitor with Statin Therapy for Intracranial Artery Stenosis ( PISTIAS): Rationale and design of a multicenter randomized controlled trial.
Rationale: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors enable an additional 54-75% reduction in low-density lipoprotein cholesterol (LDL-C) in statin-treated patients, demonstrating plaque regression in coronary artery disease. However, the impact of achieving an extremely low level of LDL-C with PCSK9 inhibitors (e.g. Evolocumab) on symptomatic intracranial atherosclerosis remains unexplored.
Aim and hypothesis: To determine whether combining Evolocumab and statins achieves a more significant symptomatic intracranial plaque regression than statin therapy alone.
Sample size estimates: With a sample size of 1000 subjects, a two-sided α of 0.05, and 20% lost to follow-up, the study will have 83.3% power to detect the difference in intracranial plaque burden.
Methods and design: This is an investigator-initiated multicenter, randomized, open-label, outcome assessor-blinded trial, evaluating the impact of combining Evolocumab and statins on intracranial plaque burden assessed by high-resolution magnetic resonance imaging at baseline in patients undergoing a clinically indicated acute stroke or transient ischemic attack due to intracranial artery stenosis, and after 24 weeks of treatment. Subjects (n = 1000) were randomized 1:1 into two groups to receive either Evolocumab 140 mg every 2 weeks with statin therapy or statin therapy alone.
Study outcomes: The primary endpoint is the change in intracranial plaque burden assessed by high-resolution magnetic resonance imaging, performed at baseline and at the end of the 24-week treatment period.
Discussion: This trial will explore whether more significant intracranial plaque regression is achievable with the treatment of combining Evolocumab and statins, providing information about efficacy and safety data.
期刊介绍:
The International Journal of Stroke is a welcome addition to the international stroke journal landscape in that it concentrates on the clinical aspects of stroke with basic science contributions in areas of clinical interest. Reviews of current topics are broadly based to encompass not only recent advances of global interest but also those which may be more important in certain regions and the journal regularly features items of news interest from all parts of the world. To facilitate the international nature of the journal, our Associate Editors from Europe, Asia, North America and South America coordinate segments of the journal.