ImportanceIn patients with atherosclerotic cardiovascular disease (ASCVD), intensive lowering of low-density lipoprotein (LDL) cholesterol levels with high-intensity statins is generally recommended. However, alternative approaches considering statin-related adverse effects and intolerance are needed.ObjectiveTo 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.Data SourcesPubMed, Embase, and other websites (ClinicalTrials.gov, European Society of Cardiology, tctMD) were systematically searched from inception to April 19, 2024.Study SelectionRandomized 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.Data Extraction and SynthesisIndividual 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). 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. The primary analysis was based on a 1-stage approach.Main Outcomes and MeasuresThe primary end point was a 3-year composite of all-cause death, myocardial infarction, stroke, or coronary revascularization. The secondary end points comprised clinical efficacy and safety end points.ResultsIndividual 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. 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). 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). 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).Conclusions and RelevanceResults of this systematic review and individual patient data meta-analysis suggest 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.Study RegistrationPROSPERO CRD42024532550

中文翻译：

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动脉粥样硬化性心血管疾病中的替代 LDL 胆固醇降低策略与高强度他汀类药物


重要性对于动脉粥样硬化性心血管疾病 （ASCVD） 患者，通常建议使用高强度他汀类药物强化降低低密度脂蛋白 （LDL） 胆固醇水平。然而，需要考虑他汀类药物相关不良反应和不耐受的替代方法。目的在随机临床试验中比较替代 LDL 胆固醇降低策略与高强度他汀类药物策略在 ASCVD 患者中的长期疗效和安全性。数据来源从建库到 2024 年 4 月 19 日系统检索了 PubMed、Embase 和其他网站（ClinicalTrials.gov，欧洲心脏病学会，tctMD）。研究选择随机临床试验比较了 ASCVD 患者替代的 LDL 降胆固醇策略与高强度他汀类药物策略，以心血管事件为终点。数据提取和综合个体患者数据来自符合预先设定的资格标准的随机临床试验：RACING（他汀类药物单药治疗与他汀类/依折麦布联合治疗高危心血管疾病的降脂疗效和安全性随机比较）和 LODESTAR（冠状动脉疾病患者的低密度脂蛋白胆固醇靶向他汀类药物治疗与基于强度的他汀类药物治疗）。RACING 试验中的中等强度他汀类药物与依折麦布联合治疗和 LODESTAR 试验中的治疗到目标策略被归类为替代的 LDL 胆固醇降低策略。主要分析基于 1 阶段方法。主要结局和测量主要终点是全因死亡、心肌梗死、中风或冠状动脉血运重建的 3 年复合。 次要终点包括临床疗效和安全性终点。结果分析了来自 2 项试验的个体患者数据，包括 8180 名 ASCVD 患者 （平均 [SD] 年龄，64.5 [9.8] 岁;2182 名 [26.7%] 女性;5998 名男性 [73.3%]）。替代策略组和高强度他汀类药物策略组之间的主要终点发生率没有差异 （7.5% [4094 例中的 304 例] vs 7.7% [4086 例中的 310 例];风险比，0.98;95% CI，0.84-1.15;P = .82）。替代策略组治疗期间平均 （SD） LDL 胆固醇水平为 64.8 （19.0） mg/dL，高强度他汀类药物策略组为 68.5 （20.7） mg/dL （P < .001）。替代策略组的新发糖尿病发生率较低 （10.2% [2658 例中的 271 例] 对 11.9% [2656 例中的 316 例];P = .047），开始抗糖尿病药物治疗新发糖尿病 （6.5% [2658 中的 173] 对 8.2% [2656 中的 217] ;P = .02），以及与不耐受相关的指定治疗的停药或剂量减少 （4.0% [4094 中的 163] 对 6.7% [4086 中的 273] ;P < .001）。结论和相关性本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，替代性 LDL 降胆固醇策略在 ASCVD 患者 3 年死亡或心血管事件方面显示出相当的疗效，与 LDL 胆固醇水平和新发糖尿病和不耐受的风险相关降低。研究注册PROSPERO CRD42024532550