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.

中文翻译：

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中等强度他汀类药物与依折麦布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 (RACING) 患者的长期疗效和安全性：一项随机、开放标签、非劣效性试验

背景

药物组合而不是增加一种药物的剂量可以获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疗法的替代方案，中等强度他汀类药物与依折麦布联合治疗可以有效降低 LDL 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结果。

方法

在这项随机、开放标签、非劣效性试验中，韩国 26 个临床中心的动脉粥样硬化性心血管疾病 (ASCVD) 患者被随机分配 (1:1) 接受中等强度他汀类药物联合依折麦布治疗（瑞舒伐他汀 10毫克与依折麦布 10 毫克）或高强度他汀类药物单一疗法（瑞舒伐他汀 20 毫克）。主要终点是意向治疗人群中心血管死亡、主要心血管事件或非致命性卒中的 3 年复合终点，非劣效性界值为 2·0%。该试验已在 ClinicalTrials.gov 注册，NCT03044665 并且已经完成。

发现

2017 年 2 月 14 日至 2018 年 12 月 18 日期间，共招募了 3780 名患者：联合治疗组 1894 名患者和高强度他汀类药物单一治疗组 1886 名患者。主要终点发生在联合治疗组的 172 名患者 (9·1%) 和高强度他汀类药物单药治疗组的 186 名患者 (9·9%) 中（绝对差异 -0·78%；90% CI -2· 39 至 0·83）。联合治疗组 73%、75% 和 72% 的患者以及 55%、60% 和 58% 的患者在 1、2 和 3 年时观察到 LDL 胆固醇浓度低于 70 mg/dL在高强度他汀类药物单一疗法组（所有 p<0·0001）。分别有 88 名 (4·8%) 和 150 名 (8·2%) 患者 (p<0·0001) 因不耐受而停用研究药物或减少剂量。

解释

在 ASCVD 患者中，中等强度他汀类药物与依折麦布联合治疗的 3 年复合结局不劣于高强度他汀类药物单药治疗，LDL 胆固醇浓度低于 70 mg/dL 且耐受性较低的患者比例更高-相关的药物停药或剂量减少。

资金

韩美制药。