1991-LB: Cardiovascular Efficacy of Evolocumab in Persons with Type 1 Diabetes Mellitus—Insights from FOURIER Trial

IF 7.5 1区医学 Q1 ENDOCRINOLOGY & METABOLISM

Diabetes Pub Date : 2025-06-20 DOI:10.2337/db25-1991-lb

YU MI KANG, ROBERT P. GIUGLIANO, XINHUI RAN, PRAKASH DEEDWANIA, GAETANO M. DE FERRARI, JYOTHIS T. GEORGE, IOANNA GOUNI-BERTHOLD, GABRIEL PAIVA DA SILVA LIMA, YEHUDA HANDELSMAN, BASIL S. LEWIS, E. MAGNUS OHMAN, ANTHONY C. KEECH, HUEI WANG, MARC S. SABATINE, LAWRENCE A. LEITER

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The primary endpoint (PEP) was CV death, MI, stroke, hospitalization for unstable angina, or coronary revascularization. The key secondary endpoint (SEP) was CV death, MI, or stroke. Hazard ratios (HR) and absolute risk reductions (ARR) with evolocumab vs. placebo were compared among pts w/o diabetes (no DM), with type 2 diabetes (T2D), and with T1D. Results: Of 27,564 pts, 197 (0.7%) had T1D. Their median (IQR) age was 58 (53-64) yrs and duration of diabetes 28 yrs. In the placebo arm, there was a stepwise increase in the 2.5-y KM rate of the PEP, going from 11.0% to 15.2% to 20.4% in pts w/ no DM, T2D, and T1D, respectively (p&lt;0.0001; Fig). Evolocumab reduced the risk of the PEP by 13% (HR 0.87; 95% CI 0.73-0.96), 16% (HR 0.84 [0.75-0.93]), and 34% (HR 0.66 [0.32-1.38]), respectively. Corresponding ARRs were 1.3%, 2.5%, and 7.3%. Similar trends were seen for the key SEP. Conclusion: T1D pts with ASCVD face elevated MACE risk, and intensive LDL-C lowering with evolocumab appears to provide substantial clinical benefit in this high-risk group. Disclosure Y. Kang: None. R.P. Giugliano: Research Support; Amgen Inc, Anthos Therapeutics, Daiichi Sankyo, Ionis Pharmaceuticals. Other Relationship; Amgen Inc, CADECI, Centrix, Daiichi Sankyo, Dr. Reddy's Laboratories, Korean Heart Rhythm Society, Medical Education Resources (MER), Menarini, Pfizer Inc, SHAKEHEART, SUMMEET. Consultant; Amgen Inc, AstraZeneca, Beckman Coulter, Daiichi Sankyo, Gilead Sciences, Inc, Inventiva Pharma, Novartis Pharmaceuticals Corporation, Perosphere, Samsung, Syneos Health. X. Ran: None. P. Deedwania: None. G.M. De Ferrari: Advisory Panel; Daiichi Sankyo. Board Member; Amgen Inc, Merck & Co., Inc, Novartis AG. J.T. George: Employee; Amgen Inc. I. Gouni-Berthold: Speaker's Bureau; Amgen Inc, Sanofi-Aventis Deutschland GmbH. Advisory Panel; Daiichi Sankyo. Speaker's Bureau; Novartis AG. Advisory Panel; Novartis AG. Speaker's Bureau; Ultragenyx, Daiichi Sankyo. G. Paiva da Silva Lima: Employee; Amgen Inc. Stock/Shareholder; Amgen Inc. Y. Handelsman: Research Support; Amgen Inc. Consultant; Amgen Inc. Research Support; Applied Therapeutics. Consultant; Applied Therapeutics. Research Support; Corcept Therapeutics. Consultant; Corcept Therapeutics. Research Support; Ionis Pharmaceuticals, Lilly Diabetes, Merck Sharp & Dohme Corp, Regeneron Pharmaceuticals. B.S. Lewis: Consultant; Janssen Pharmaceuticals, Inc. E. Ohman: Employee; Amgen Inc. A.C. Keech: Research Support; Abbott, Amgen Inc, ASPEN Australia, Mylan. Speaker's Bureau; Novartis AG, Pfizer Inc. Research Support; Kowa Company, Ltd. Speaker's Bureau; Sanofi. Research Support; AbbVie Inc, Viatris Inc. H. Wang: Employee; Amgen Inc. M.S. Sabatine: Research Support; Amgen Inc. Consultant; Amgen Inc. Research Support; AstraZeneca. Consultant; AstraZeneca. Research Support; Ionis Pharmaceuticals, Marea, Merck & Co., Inc, Novartis Pharmaceuticals Corporation, Verve Therapeutics. L.A. Leiter: Other Relationship; Amgen Inc. Advisory Panel; Amgen Inc. Speaker's Bureau; Amgen Inc. Other Relationship; Eli Lilly and Company. Advisory Panel; Eli Lilly and Company. Speaker's Bureau; Eli Lilly and Company. Advisory Panel; HLS Therapeutics. Speaker's Bureau; HLS Therapeutics. Advisory Panel; Merck & Co., Inc, Novartis Pharmaceuticals Corporation. Speaker's Bureau; Novartis Pharmaceuticals Corporation. Advisory Panel; Regeneron Pharmaceuticals. 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引用次数: 0

Abstract

Introduction and Objective: Despite the very high risk for macrovascular complications, there are scant data on the benefit of lipid-lowering in type 1 diabetes (T1D). We examined the clinical efficacy of intensive LDL-C lowering with the PCSK9 inhibitor evolocumab in T1D. Methods: FOURIER enrolled pts w/ stable atherosclerotic cardiovascular disease (ASCVD) on statin randomized to evolocumab or placebo (median FU 2.2y). The primary endpoint (PEP) was CV death, MI, stroke, hospitalization for unstable angina, or coronary revascularization. The key secondary endpoint (SEP) was CV death, MI, or stroke. Hazard ratios (HR) and absolute risk reductions (ARR) with evolocumab vs. placebo were compared among pts w/o diabetes (no DM), with type 2 diabetes (T2D), and with T1D. Results: Of 27,564 pts, 197 (0.7%) had T1D. Their median (IQR) age was 58 (53-64) yrs and duration of diabetes 28 yrs. In the placebo arm, there was a stepwise increase in the 2.5-y KM rate of the PEP, going from 11.0% to 15.2% to 20.4% in pts w/ no DM, T2D, and T1D, respectively (p<0.0001; Fig). Evolocumab reduced the risk of the PEP by 13% (HR 0.87; 95% CI 0.73-0.96), 16% (HR 0.84 [0.75-0.93]), and 34% (HR 0.66 [0.32-1.38]), respectively. Corresponding ARRs were 1.3%, 2.5%, and 7.3%. Similar trends were seen for the key SEP. Conclusion: T1D pts with ASCVD face elevated MACE risk, and intensive LDL-C lowering with evolocumab appears to provide substantial clinical benefit in this high-risk group. Disclosure Y. Kang: None. R.P. Giugliano: Research Support; Amgen Inc, Anthos Therapeutics, Daiichi Sankyo, Ionis Pharmaceuticals. Other Relationship; Amgen Inc, CADECI, Centrix, Daiichi Sankyo, Dr. Reddy's Laboratories, Korean Heart Rhythm Society, Medical Education Resources (MER), Menarini, Pfizer Inc, SHAKEHEART, SUMMEET. Consultant; Amgen Inc, AstraZeneca, Beckman Coulter, Daiichi Sankyo, Gilead Sciences, Inc, Inventiva Pharma, Novartis Pharmaceuticals Corporation, Perosphere, Samsung, Syneos Health. X. Ran: None. P. Deedwania: None. G.M. De Ferrari: Advisory Panel; Daiichi Sankyo. Board Member; Amgen Inc, Merck & Co., Inc, Novartis AG. J.T. George: Employee; Amgen Inc. I. Gouni-Berthold: Speaker's Bureau; Amgen Inc, Sanofi-Aventis Deutschland GmbH. Advisory Panel; Daiichi Sankyo. Speaker's Bureau; Novartis AG. Advisory Panel; Novartis AG. Speaker's Bureau; Ultragenyx, Daiichi Sankyo. G. Paiva da Silva Lima: Employee; Amgen Inc. Stock/Shareholder; Amgen Inc. Y. Handelsman: Research Support; Amgen Inc. Consultant; Amgen Inc. Research Support; Applied Therapeutics. Consultant; Applied Therapeutics. Research Support; Corcept Therapeutics. Consultant; Corcept Therapeutics. Research Support; Ionis Pharmaceuticals, Lilly Diabetes, Merck Sharp & Dohme Corp, Regeneron Pharmaceuticals. B.S. Lewis: Consultant; Janssen Pharmaceuticals, Inc. E. Ohman: Employee; Amgen Inc. A.C. Keech: Research Support; Abbott, Amgen Inc, ASPEN Australia, Mylan. Speaker's Bureau; Novartis AG, Pfizer Inc. Research Support; Kowa Company, Ltd. Speaker's Bureau; Sanofi. Research Support; AbbVie Inc, Viatris Inc. H. Wang: Employee; Amgen Inc. M.S. Sabatine: Research Support; Amgen Inc. Consultant; Amgen Inc. Research Support; AstraZeneca. Consultant; AstraZeneca. Research Support; Ionis Pharmaceuticals, Marea, Merck & Co., Inc, Novartis Pharmaceuticals Corporation, Verve Therapeutics. L.A. Leiter: Other Relationship; Amgen Inc. Advisory Panel; Amgen Inc. Speaker's Bureau; Amgen Inc. Other Relationship; Eli Lilly and Company. Advisory Panel; Eli Lilly and Company. Speaker's Bureau; Eli Lilly and Company. Advisory Panel; HLS Therapeutics. Speaker's Bureau; HLS Therapeutics. Advisory Panel; Merck & Co., Inc, Novartis Pharmaceuticals Corporation. Speaker's Bureau; Novartis Pharmaceuticals Corporation. Advisory Panel; Regeneron Pharmaceuticals. Funding Dr Kang is funded by a T32 postdoctoral training grant from the National Institute of Diabetes and Digestive and Kidney Diseases (5T32DK007529).

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1991-LB: Evolocumab对1型糖尿病患者的心血管疗效——FOURIER试验的见解

简介和目的：尽管1型糖尿病（T1D）的大血管并发症风险很高，但关于降脂的益处的数据很少。我们研究了在T1D患者中使用PCSK9抑制剂evolocumab强化降低LDL-C的临床疗效。方法：傅里叶纳入了他汀类药物治疗的稳定动脉粥样硬化性心血管疾病（ASCVD）患者，随机分为evolocumab或安慰剂（中位FU 2.2y）。主要终点（PEP）为CV死亡、心肌梗死、卒中、不稳定型心绞痛住院或冠状动脉血运重建术。关键次要终点（SEP）是CV死亡、MI或卒中。在无糖尿病（非DM）、2型糖尿病（T2D）和T1D患者中比较evolocumab与安慰剂的风险比（HR）和绝对风险降低（ARR）。结果：27,564例患者中，197例（0.7%）为T1D。他们的中位（IQR）年龄为58（53-64）岁，糖尿病持续时间为28年。在安慰剂组中，PEP的2.5 y KM率逐步增加，在无DM、T2D和T1D的患者中分别从11.0%增加到15.2%到20.4% (p<0.0001；图)。Evolocumab使PEP风险降低13% (HR 0.87；95% CI 0.73-0.96)、16% （HR 0.84[0.75-0.93]）和34% （HR 0.66[0.32-1.38]）。相应的arr分别为1.3%、2.5%和7.3%。结论：合并ASCVD的T1D患者面临MACE风险升高，evolocumab强化降低LDL-C似乎为这一高危人群提供了实质性的临床益处。披露：没有。R.P. Giugliano：研究支持；安进公司，Anthos Therapeutics, Daiichi Sankyo， Ionis制药公司。其他关系;安进公司、CADECI、Centrix、Daiichi Sankyo、Dr. Reddy’s Laboratories、韩国心律学会、医学教育资源（MER）、美纳里尼、辉瑞公司、SHAKEHEART、SUMMEET。顾问;安进公司、阿斯利康公司、贝克曼库尔特公司、第一三共公司、吉利德科学公司、Inventiva Pharma公司、诺华制药公司、Perosphere公司、三星公司、Syneos Health公司。X. Ran：没有。P. Deedwania：没有。通用法拉利：顾问小组；第一三共制药。董事会成员;安进公司、默克公司；诺华股份有限公司J.T.乔治：雇员；安进公司。1 . Gouni-Berthold：发言人局；安进公司、赛诺菲-安万特德国有限公司顾问小组;第一三共制药。演讲者的局;诺华公司。顾问小组;诺华公司。演讲者的局;Ultragenyx, Daiichi Sankyo。G. Paiva da Silva Lima：雇员；安进公司。股票/股东;安进公司。Y. Handelsman：研究支持；安进公司。顾问;安进公司。研究支持;应用治疗。顾问;应用治疗。研究支持;Corcept疗法。顾问;Corcept疗法。研究支持;Ionis Pharmaceuticals, Lilly Diabetes, Merck Sharp &；Dohme公司，Regeneron制药公司。B.S.刘易斯：顾问；杨森制药公司E.欧曼：雇员；安进公司。A.C. Keech：研究支持；雅培，安进公司，ASPEN澳大利亚，迈兰。演讲者的局;诺华公司、辉瑞公司研究支持;科华株式会社演讲者的局;赛诺菲。研究支持;艾伯维公司、Viatris公司H. Wang：员工；安进公司。萨巴蒂纳硕士：研究支持；安进公司。顾问;安进公司。研究支持;阿斯利康。顾问;阿斯利康。研究支持;Ionis Pharmaceuticals, Marea, Merck &；诺华制药公司，Verve Therapeutics。L.A. Leiter：其他关系；安进公司。顾问小组;安进公司。演讲者的局;安进公司。其他关系;礼来公司。顾问小组;礼来公司。演讲者的局;礼来公司。顾问小组;HLS疗法。演讲者的局;HLS疗法。顾问小组;默克公司,诺华制药有限公司演讲者的局;诺华制药公司。顾问小组;Regeneron药品。康博士获得国家糖尿病、消化和肾脏疾病研究所T32博士后培养资助（5T32DK007529）。

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来源期刊

Diabetes 医学-内分泌学与代谢

CiteScore

12.50

自引率

2.60%

发文量

1968

审稿时长

1 months

期刊介绍： Diabetes is a scientific journal that publishes original research exploring the physiological and pathophysiological aspects of diabetes mellitus. We encourage submissions of manuscripts pertaining to laboratory, animal, or human research, covering a wide range of topics. Our primary focus is on investigative reports investigating various aspects such as the development and progression of diabetes, along with its associated complications. We also welcome studies delving into normal and pathological pancreatic islet function and intermediary metabolism, as well as exploring the mechanisms of drug and hormone action from a pharmacological perspective. Additionally, we encourage submissions that delve into the biochemical and molecular aspects of both normal and abnormal biological processes. However, it is important to note that we do not publish studies relating to diabetes education or the application of accepted therapeutic and diagnostic approaches to patients with diabetes mellitus. Our aim is to provide a platform for research that contributes to advancing our understanding of the underlying mechanisms and processes of diabetes.