Alternative LDL Cholesterol-Lowering Strategy vs High-Intensity Statins in Atherosclerotic Cardiovascular Disease: A Systematic Review and Individual Patient Data Meta-Analysis.

However, alternative approaches considering statin-related adverse effects and intolerance are needed.

然而，考虑到他汀类药物相关的不良反应和不耐受性，需要考虑其他替代方法。

Background

To compare the long-term efficacy and safety of an alternative LDL cholesterol-lowering strategy vs high-intensity statin strategy in patients with ASCVD in randomized clinical trials.

在随机临床试验中比较替代性降低LDL胆固醇策略与高强度他汀类药物策略在动脉粥样硬化性心血管疾病（ASCVD）患者中的长期疗效和安全性。

data_sources

PubMed, Embase, and other websites (ClinicalTrials.gov, European Society of Cardiology, tctMD) were systematically searched from inception to April 19, 2024.

从创建之初至2024年4月19日，系统性地检索了PubMed、Embase以及其他网站（ClinicalTrials.gov、欧洲心脏病学会、tctMD）以获取相关资料。

study_selection

Randomized clinical trials comparing an alternative LDL cholesterol-lowering strategy vs a high-intensity statin strategy in patients with ASCVD, with presence of cardiovascular events as end points.

随机临床试验比较了在动脉粥样硬化性心血管疾病（ASCVD）患者中，采用一种替代的低密度脂蛋白胆固醇（LDL-C）降低策略与高强度他汀类药物策略，以心血管事件的发生为终点。

data_extraction_and_synthesis

Individual patient data were obtained from randomized clinical trials that met the prespecified eligibility criteria: RACING (Randomized Comparison of Efficacy and Safety of Lipid-Lowering With Statin Monotherapy vs Statin/Ezetimibe Combination for High-Risk Cardiovascular Disease) and LODESTAR (Low-Density Lipoprotein Cholesterol-Targeting Statin Therapy vs Intensity-Based Statin Therapy in Patients With Coronary Artery Disease).

从符合预先设定的纳入标准的随机临床试验中获取了个体患者数据：RACING（随机比较他汀单药治疗与他汀/依折麦布联合治疗在高风险心血管疾病中的疗效和安全性）和LODESTAR（针对冠状动脉疾病患者的低密度脂蛋白胆固醇靶向他汀治疗与基于强度的他汀治疗）。

The moderate-intensity statin with ezetimibe combination therapy in the RACING trial and the treat-to-target strategy in the LODESTAR trial were classified as alternative LDL cholesterol-lowering strategies.

RACING试验中的中等强度他汀联合依折麦布治疗以及LODESTAR试验中的靶向治疗策略被归类为替代的低密度脂蛋白胆固醇降低策略。

The primary analysis was based on a 1-stage approach.

主要分析基于单阶段方法。

main_outcomes_and_measures

The primary end point was a 3-year composite of all-cause death, myocardial infarction, stroke, or coronary revascularization.

主要终点是3年内全因死亡、心肌梗死、中风或冠状动脉血运重建的复合结果。

The secondary end points comprised clinical efficacy and safety end points.

次要终点包括临床疗效和安全性终点。

Results

Individual patient data from 2 trials including 8180 patients with ASCVD (mean [SD] age, 64.5 [9.8] years; 2182 [26.7%] female; 5998 male [73.3%]) were analyzed.

分析了2项试验中8180名动脉粥样硬化性心血管疾病（ASCVD）患者的个体患者数据（平均[标准差]年龄为64.5[9.8]岁；女性2182名[26.7%]；男性5998名[73.3%]）

The rate of the primary end point did not differ between the alternative strategy and high-intensity statin strategy groups (7.5% [304 of 4094] vs 7.7% [310 of 4086]; hazard ratio, 0.98; 95% CI, 0.84-1.15; P = .82).

主要终点事件的发生率在替代策略组和高强度他汀策略组之间没有差异（7.5% [304/4094] 对比 7.7% [310/4086]；风险比，0.98；95% 置信区间，0.84-1.15；P = .82）

The mean (SD) LDL cholesterol level during treatment was 64.8 (19.0) mg/dL in the alternative strategy group and 68.5 (20.7) mg/dL in the high-intensity statin strategy group (P < .001).

治疗期间，替代策略组的平均（标准差）LDL胆固醇水平为64.8（19.0）mg/dL，高强度他汀策略组为68.5（20.7）mg/dL（P < .001）。

The alternative strategy group had a lower rate of new-onset diabetes (10.2% [271 of 2658] vs 11.9% [316 of 2656]; P = .047), initiation of antidiabetic medication for new-onset diabetes (6.5% [173 of 2658] vs 8.2% [217 of 2656]; P = .02), and intolerance-related discontinuation or dose reduction of assigned therapy (4.0% [163 of 4094] vs 6.7% [273 of 4086]; P < .001).

替代策略组的新发糖尿病率较低（10.2% [271/2658] 对比 11.9% [316/2656]；P = .047），新发糖尿病开始使用抗糖尿病药物的比率也较低（6.5% [173/2658] 对比 8.2% [217/2656]；P = .02），以及因不耐受导致的指定治疗中断或剂量减少的比率较低（4.0% [163/4094] 对比 6.7% [273/4086]；P < .001）。

conclusions_and_relevance

Results of this systematic reviewand individual patient data meta-analysissuggest that compared with a high-intensity statin strategy, the alternative LDL cholesterol-lowering strategy demonstrated comparable efficacy regarding 3-year death or cardiovascular events in patients with ASCVD, with an associated reduction in LDL cholesterol levels and risk for new-onset diabetes and intolerance.

这项系统评价和个体患者数据荟萃分析的结果表明，与高强度他汀类药物策略相比，另一种降低LDL胆固醇的策略在降低 ASCVD 患者3年内死亡或心血管事件方面具有相当的疗效，同时降低了LDL胆固醇水平，并减少了新发糖尿病和不耐受的风险。

study_registration

PROSPERO CRD42024532550.

PROSPERO CRD42024532550。