韩国延世大学医学院Myeong-Ki Hong团队联合抱川中文医科大学Yangsoo Jang团队比较了中强度他汀类药物与依折米贝联合治疗与高强度他汀类药物单药治疗动脉粥样硬化性心血管疾病患者的长期疗效和安全性。这一研究成果发表在2022年7月18日出版的《柳叶刀》杂志上。

联合用药而非增加一种药物的剂量可以取得更大的疗效和更低的风险。因此，作为高强度他汀类药物单一治疗的替代方案，中等强度他汀类药物与依折米贝联合治疗可以有效降低低密度脂蛋白胆固醇浓度，同时减少不良反应。然而，需要来自随机试验的证据来比较长期临床预后。

研究组在韩国26个临床中心进行了一项随机、开放标签、非劣效性试验，招募动脉粥样硬化性心血管疾病（ASCVD）患者，将其按1：1随机分配，分别接受中等强度他汀类药物与依折米贝联合治疗（瑞舒伐他汀10 mg与依折米贝10 mg）或高强度他汀类药物单药治疗（瑞舒伐他汀20 mg）。主要终点是心血管死亡、重大心血管事件或非致命性卒中的3年复合终点，所有治疗人群的非劣效性边缘为2.0%。

2017年2月14日至2018年12月18日，研究组共招募了3780名患者：其中1894名加入联合治疗组，1886名加入高强度他汀类药物单药治疗组。联合治疗组中有172名患者（9.1%）发生主要终点，高强度他汀单药治疗组中有186名（9.9%），绝对差异为−0.78%。

联合治疗组中分别有73%、75%和72%的患者在1年、2年和3年时LDL胆固醇浓度低于70 mg/dL，而高强度他汀类药物单药治疗组中分别有55%、60%和58%的患者，组间差异均显著。联合治疗组中有88名患者（4.8%）因不耐受而中断或减少研究药物剂量，而高强度他汀类药物单药治疗组中有150名患者（8.2%）。

研究结果表明，对于ASCVD患者，中等强度他汀类药物与依折米贝联合治疗在3年综合疗效方面并不劣于高强度他汀类药物单药治疗，但低密度脂蛋白胆固醇浓度低于70 mg/dL的患者比例显著提高，与不耐受相关的停药或剂量减少的患者比例显著降低。

附：英文原文

Title: Long-term efficacy and safety of moderate-intensity statin with ezetimibe combination therapy versus high-intensity statin monotherapy in patients with atherosclerotic cardiovascular disease (RACING): a randomised, open-label, non-inferiority trial

Author: Byeong-Keuk Kim, Sung-Jin Hong, Yong-Joon Lee, Soon Jun Hong, Kyeong Ho Yun, Bum-Kee Hong, Jung Ho Heo, Seung-Woon Rha, Yun-Hyeong Cho, Seung-Jun Lee, Chul-Min Ahn, Jung-Sun Kim, Young-Guk Ko, Donghoon Choi, Yangsoo Jang, Myeong-Ki Hong

Issue&Volume: 2022-07-18

Abstract:

Background

Drug combinations rather than increasing doses of one drug can achieve greater efficacy and lower risks. Thus, as an alternative to high-intensity statin monotherapy, moderate-intensity statin with ezetimibe combination therapy can lower LDL cholesterol concentrations effectively while reducing adverse effects. However, evidence from randomised trials to compare long-term clinical outcomes is needed.

Methods

In this randomised, open-label, non-inferiority trial, patients with atherosclerotic cardiovascular disease (ASCVD) at 26 clinical centres in South Korea were randomly assigned (1:1) to receive either moderate-intensity statin with ezetimibe combination therapy (rosuvastatin 10 mg with ezetimibe 10 mg) or high-intensity statin monotherapy (rosuvastatin 20 mg). The primary endpoint was the 3-year composite of cardiovascular death, major cardiovascular events, or non-fatal stroke, in the intention-to-treat population with a non-inferiority margin of 2·0%. This trial is registered with ClinicalTrials.gov, NCT03044665 and is complete.

Findings

Between Feb 14, 2017, and Dec 18, 2018, 3780 patients were enrolled: 1894 patients to the combination therapy group and 1886 to the high-intensity statin monotherapy group. The primary endpoint occurred in 172 patients (9·1%) in the combination therapy group and 186 patients (9·9%) in the high-intensity statin monotherapy group (absolute difference 0·78%; 90% CI 2·39 to 0·83). LDL cholesterol concentrations of less than 70 mg/dL at 1, 2, and 3 years were observed in 73%, 75%, and 72% of patients in the combination therapy group, and 55%, 60%, and 58% of patients in the high-intensity statin monotherapy group (all p<0·0001). Discontinuation or dose reduction of the study drug by intolerance was observed in 88 patients (4·8%) and 150 patients (8·2%), respectively (p<0·0001).

Interpretation

Among patients with ASCVD, moderate-intensity statin with ezetimibe combination therapy was non-inferior to high-intensity statin monotherapy for the 3-year composite outcomes with a higher proportion of patients with LDL cholesterol concentrations of less than 70 mg/dL and lower intolerance-related drug discontinuation or dose reduction.

DOI: 10.1016/S0140-6736(22)00916-3

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(22)00916-3/fulltext