瑞西伐他汀与依折麦布联合中等强度他汀治疗与高强度他汀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（RACING）：一项随机、开放标签、非劣效性试验。

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.

机构信息

Division of Cardiology, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea.

Korea University College of Medicine, Seoul, South Korea.

出版信息

Lancet. 2022 Jul 30;400(10349):380-390. doi: 10.1016/S0140-6736(22)00916-3. Epub 2022 Jul 18.

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

PMID:35863366

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.

FUNDING

Hanmi Pharmaceutical.

摘要

背景

药物联合治疗而非增加单药剂量可以提高疗效并降低风险。因此，与高强度他汀类药物单药治疗相比，中等强度他汀类药物联合依折麦布治疗可以有效降低 LDL 胆固醇浓度，同时降低不良反应。然而，需要随机试验的证据来比较长期的临床结局。

方法

本项在韩国 26 个临床中心进行的随机、开放标签、非劣效性试验中，将 26 个临床中心的动脉粥样硬化性心血管疾病（ASCVD）患者（n=3780）按 1:1 比例随机分配（随机分配）接受中等强度他汀类药物联合依折麦布治疗（瑞舒伐他汀 10mg+依折麦布 10mg）或高强度他汀类药物单药治疗（瑞舒伐他汀 20mg）。主要终点是意向治疗人群的 3 年复合终点，包括心血管死亡、主要心血管事件或非致命性卒中，非劣效性边界为 2.0%。本试验在 ClinicalTrials.gov 注册，NCT03044665，现已完成。

结果

2017 年 2 月 14 日至 2018 年 12 月 18 日期间，共纳入 3780 例患者：联合治疗组 1894 例，高强度他汀类药物单药治疗组 1886 例。联合治疗组 172 例（9.1%）和高强度他汀类药物单药治疗组 186 例（9.9%）发生主要终点事件（绝对差值-0.78%；90%CI-2.39 至 0.83）。联合治疗组分别有 73%、75%和 72%的患者在 1、2 和 3 年时 LDL 胆固醇浓度<70mg/dL，高强度他汀类药物单药治疗组分别有 55%、60%和 58%的患者 LDL 胆固醇浓度<70mg/dL（均 p<0.0001）。不耐受导致研究药物停药或剂量减少的分别有 88 例（4.8%）和 150 例（8.2%）（p<0.0001）。