当前位置: X-MOL 学术Lancet Diabetes Endocrinol. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Metabolic risk factors and effect of alirocumab on cardiovascular events after acute coronary syndrome: a post-hoc analysis of the ODYSSEY OUTCOMES randomised controlled trial
The Lancet Diabetes & Endocrinology ( IF 44.5 ) Pub Date : 2022-04-01 , DOI: 10.1016/s2213-8587(22)00043-2
Petr Ostadal 1 , Philippe Gabriel Steg 2 , Yann Poulouin 3 , Deepak L Bhatt 4 , Vera A Bittner 5 , Terrence Chua 6 , Rafael Diaz 7 , Shaun G Goodman 8 , Yong Huo 9 , Johan Wouter Jukema 10 , Yuri Karpov 11 , Robert Pordy 12 , Michel Scemama 13 , Michael Szarek 14 , Harvey D White 15 , Gregory G Schwartz 16 ,
Affiliation  

Background

Many patients with acute coronary syndrome have concurrent metabolic risk factors that affect risk of major adverse cardiovascular events (MACE). We aimed to assess the effects of the PCSK9 inhibitor alirocumab compared with placebo on MACE according to baseline metabolic risk factors.

Methods

We performed a post-hoc analysis of the ODYSSEY OUTCOMES trial, which was a multicentre, double-blind, randomised controlled trial done in 1315 hospitals and outpatient clinics in 57 countries. Patients aged 40 years or older with recent acute coronary syndrome (ie, in the past 1–12 months) and elevated concentrations of atherogenic lipoproteins, despite high-intensity or maximum-tolerated statin treatment, were eligible for enrolment. Between Nov 2, 2012, and Feb 9, 2017, patients were randomly assigned (1:1) to 75 mg alirocumab by subcutaneous injection every 2 weeks or matching placebo, beginning 1–12 months after acute coronary syndrome and were followed up for a median of 2·8 years (IQR 2·3–3·4). Patients and investigators were masked to group assignment and treatment dose adjustment. The primary outcome was a composite of death from coronary artery disease, non-fatal myocardial infarction, fatal or non-fatal ischaemic stroke, or unstable angina requiring hospital admission. Analysis of MACE according to an ordinal number of metabolic risk factors was done post hoc. Metabolic risk factors were defined as blood pressure of at least 130/85 mm Hg or treatment with antihypertensive medication, triglyceride concentration of at least 150 mg/dL, HDL cholesterol concentration less than 40 mg/dL for men and 50 mg/dL women, fasting plasma glucose concentration of at least 100 mg/dL or treatment with glucose-lowering medication, and BMI of at least 30 kg/m2. Risk of MACE and effect of alirocumab were assessed according to the number of metabolic risk factors. ODYSSEY OUTCOMES is registered with ClinicalTrials.gov, number NCT01663402.

Findings

Of 18 924 patients, 3882 (41%) of 9462 in the alirocumab group and 3859 (41%) of 9462 in the placebo group had three or more metabolic risk factors. In the placebo group, MACE incidence increased monotonically with each metabolic risk factor from 7·8% (no risk factors) to 19·6% (five risk factors; HR 1·18, 95% CI 1·13–1·24 per metabolic risk factor). Alirocumab decreased relative risk of MACE consistently across categories defined by the number of metabolic risk factors (pinteraction=0·77), but absolute risk reduction (aRR) increased with the number of metabolic risk factors (no risk factors aRR 0·7%, –1·81 to 3·29 vs five risk factors aRR 3·9%, –1·45 to 9·25; pinteraction<0·001). Similarly, when patients with diabetes were excluded, the incidence of MACE in the placebo group increased from 7·7% in patients with no metabolic risk factors to 14·6% in those with five metabolic risk factors and aRR with alirocumab increased from 0·91% in patients with no metabolic risk factors to 3·82% in those with five factors. Alirocumab was well tolerated in all subgroups defined by the presence of metabolic risk factors.

Interpretation

Accumulation of metabolic risk factors was associated with higher risk of MACE in patients with recent acute coronary syndrome. Alirocumab reduced MACE consistently, but aRR increased with number of metabolic risk factors.

Funding

Sanofi and Regeneron Pharmaceuticals.



中文翻译:

alirocumab 对急性冠状动脉综合征后心血管事件的代谢危险因素和影响:对 ODYSSEY OUTCOMES 随机对照试验的事后分析

背景

许多急性冠状动脉综合征患者同时存在影响主要不良心血管事件 (MACE) 风险的代谢危险因素。我们旨在根据基线代谢危险因素评估 PCSK9 抑制剂 alirocumab 与安慰剂相比对 MACE 的影响。

方法

我们对 ODYSSEY OUTCOMES 试验进行了事后分析,这是一项在 57 个国家的 1315 家医院和门诊进行的多中心、双盲、随机对照试验。尽管接受了高强度或最大耐受的他汀类药物治疗,但年龄在 40 岁或以上且近期患有急性冠状动脉综合征(即在过去 1-12 个月内)和致动脉粥样硬化脂蛋白浓度升高的患者符合入组条件。在 2012 年 11 月 2 日至 2017 年 2 月 9 日期间,患者被随机分配 (1:1) 至每 2 周皮下注射 75 mg alirocumab 或匹配安慰剂,从急性冠状动脉综合征后 1-12 个月开始,并随访2·8 年的中位数(IQR 2·3–3·4)。患者和研究人员对分组分配和治疗剂量调整不知情。主要结局是冠状动脉疾病死亡、非致死性心肌梗死、致死性或非致死性缺血性卒中或需要住院治疗的不稳定型心绞痛的复合结局。根据代谢危险因素的序数对 MACE 进行了事后分析。代谢危险因素定义为血压至少 130/85 mmHg 或使用抗高血压药物治疗,甘油三酯浓度至少 150 mg/dL,HDL 胆固醇浓度男性低于 40 mg/dL,女性 50 mg/dL,空腹血糖浓度至少为 100 mg/dL 或接受降糖药物治疗,且 BMI 至少为 30 kg/m 根据代谢危险因素的序数对 MACE 进行了事后分析。代谢危险因素定义为血压至少 130/85 mmHg 或使用抗高血压药物治疗,甘油三酯浓度至少 150 mg/dL,HDL 胆固醇浓度男性低于 40 mg/dL,女性 50 mg/dL,空腹血糖浓度至少为 100 mg/dL 或接受降糖药物治疗,且 BMI 至少为 30 kg/m 根据代谢危险因素的序数对 MACE 进行了事后分析。代谢危险因素定义为血压至少 130/85 mmHg 或使用抗高血压药物治疗,甘油三酯浓度至少 150 mg/dL,HDL 胆固醇浓度男性低于 40 mg/dL,女性 50 mg/dL,空腹血糖浓度至少为 100 mg/dL 或接受降糖药物治疗,且 BMI 至少为 30 kg/m2 . 根据代谢危险因素的数量评估 MACE 的风险和 alirocumab 的效果。ODYSSEY OUTCOMES 在 ClinicalTrials.gov 注册,编号为 NCT01663402。

发现

在 18924 名患者中,alirocumab 组的 9462 名患者中有 3882 名(41%)和安慰剂组的 9462 名患者中有 3859 名(41%)有三个或更多代谢危险因素。在安慰剂组中,MACE 发生率随着每个代谢风险因素从 7·8%(无风险因素)单调增加至 19·6%(五个风险因素;HR 1·18,95% CI 1·13–1·24 每代谢危险因素)。Alirocumab 始终如一地降低由代谢风险因素数量定义的类别的 MACE 相对风险(p交互作用=0·77),但绝对风险降低(aRR)随着代谢风险因素数量的增加而增加(无风险因素 aRR 0·7% , –1·81 至 3·29五个风险因素 aRR 3·9%, –1·45 至 9·25;p交互作用<0·001)。同样,当排除糖尿病患者时,安慰剂组的 MACE 发生率从没有代谢危险因素的患者的 7·7% 增加到有 5 个代谢危险因素的患者的 14·6%,alirocumab 的 aRR 从 0· 91%在无代谢危险因素的患者中,3·82%在有五种因素的患者中。Alirocumab 在由存在代谢危险因素定义的所有亚组中均具有良好的耐受性。

解释

代谢危险因素的积累与近期急性冠状动脉综合征患者的 MACE 风险升高相关。Alirocumab 持续降低 MACE,但 aRR 随着代谢危险因素的增加而增加。

资金

赛诺菲和再生元制药。

更新日期:2022-04-01
down
wechat
bug