近日，加拿大圣迈克尔斯医院C David Mazer团队研究了evolocumab对冠状动脉旁路移植术后大隐静脉通畅性的影响。2025年9月2日出版的《柳叶刀》杂志发表了这项成果。

冠状动脉旁路移植术（CABG）后，隐静脉移植（SVG）失败仍然是一个重大挑战。低密度脂蛋白胆固醇（LDL-C）是动脉粥样硬化的一个因果危险因素，但其在SVG失败中的作用尚未得到很好的证实。研究组评估早期开始使用evolocumab强化降低LDL-C是否可以减少SVG失败。

研究组进行了一项多中心、双盲、随机、安慰剂对照试验，在加拿大、美国、澳大利亚和匈牙利的23个地点进行。符合条件的参与者是成年人（年龄≥18岁），接受了至少两个SVG的冠脉搭桥，并接受了中等或高强度的他汀类药物治疗。在CABG的21天内，参与者被随机分配（1:1；可变块大小），每2周皮下evolocumab 140 mg或安慰剂。主要终点是改良意向治疗人群中24个月静脉移植物发病率（VGDR；冠状动脉CT血管造影或临床指征有创血管造影时SVG闭塞≥50%的比例）。

在2019年6月17日至2022年11月10日期间，782名患者被随机分配（389人接受evolocumab治疗，393人接受安慰剂治疗）。基线时，在554名有主要结局数据的参与者中，年龄中位数为66岁（IQR 60-72）， 554名参与者中有471名（85%）为男性，83名（15%）为女性，evolocumab组的中位LDL-C为1.85 mmol/L (IQR 1.25 - 2.84)，安慰剂组的中位LDL-C为1.86 mmol/L（1.20 - 2.76）。Evolocumab在24个月时导致经安慰剂调整的LDL-C平均降低48.4%（- 52.4% vs - 4.0%）。evolocumab组24个月的VGDR为21.7%（686例移植物中有149例），安慰剂组为19.7%（644例移植物中有127例）（差异为2%；p= 0.44）。治疗耐受性良好，两组不良事件相似。

研究结果表明，在接受CABG的患者中，evolocumab在指数手术后24个月没有减少SVG疾病，尽管LDL-C显著降低。进一步降低LDL-C似乎不会对早期SVG失败的病理生理机制产生有意义的影响。

附：英文原文

Title: Effect of evolocumab on saphenous vein graft patency after coronary artery bypass surgery (NEWTON-CABG CardioLink-5): an international, randomised, double-blind, placebo-controlled trial

Author: Subodh Verma, Lawrence A Leiter, Hwee Teoh, G B John Mancini, Adrian Quan, Randi Elituv, Meena Verma, Elizabeth Misner, Michael Szarek, Kevin E Thorpe, Tarit Saha, Richard P Whitlock, Bobby Yanagawa, Béla Merkely, Peter Jüni, Michael J Koren, Stephen J Nicholls, Deepak L Bhatt, C David Mazer

Issue&Volume: 2025-09-01

Abstract:

Background

Saphenous vein graft (SVG) failure remains a substantial challenge after coronary artery bypass graft (CABG). LDL cholesterol (LDL-C) is a causal risk factor for atherosclerosis, but its role in SVG failure is not well established. We evaluated whether early initiation of intensive LDL-C lowering with evolocumab could reduce SVG failure.

Methods

NEWTON-CABG CardioLink-5 was a multicentre, double-blind, randomised, placebo-controlled trial conducted at 23 sites in Canada, the USA, Australia, and Hungary. Eligible participants were adults (age ≥18 years) who underwent CABG with at least two SVGs and were being treated with statin therapy of moderate or high intensity. Participants were randomly allocated (1:1; variable block size) within 21 days of CABG to subcutaneous evolocumab 140 mg or placebo every 2 weeks. The primary endpoint was the 24-month vein graft disease rate (VGDR; the proportion of SVGs with ≥50% occlusion on coronary CT angiography or clinically indicated invasive angiography) in the modified intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT03900026, and is completed.

Findings

Between June 17, 2019, and Nov 10, 2022, 782 individuals were randomly assigned (389 to evolocumab and 393 to placebo). At baseline, among the 554 participants with primary outcome data available, the median age was 66 years (IQR 60–72), 471 (85%) of 554 participants were male and 83 (15%) were female, and the median LDL-C was 1·85 mmol/L (IQR 1·25–2·84) in the evolocumab group and 1·86 mmol/L (1·20–2·76) in the placebo group. Evolocumab resulted in a mean 48·4% placebo-adjusted reduction in LDL-C at 24 months (–52·4% vs –4·0%). The 24-month VGDR was 21·7% (149 of 686 grafts) in the evolocumab group and 19·7% (127 of 644 grafts) in the placebo group (difference 2·0% [95% CI –3·1 to 7·1]; p=0·44). Treatment was well tolerated, with similar adverse event profiles between the groups.

Interpretation

Among patients who underwent CABG, evolocumab did not reduce SVG disease at 24 months following the index surgery despite substantial LDL-C lowering. Further LDL-C lowering does not appear to meaningfully affect the pathophysiological mechanisms responsible for early SVG failure.

DOI: 10.1016/S0140-6736(25)01633-2

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(25)01633-2/abstract