Association Between Intensity of Low-Density Lipoprotein Cholesterol Reduction With Statin-Based Therapies and Secondary Stroke Prevention: A Meta-analysis of Randomized Clinical Trials.
Association Between Intensity of Low-Density Lipoprotein Cholesterol Reduction With Statin-Based Therapies and Secondary Stroke Prevention: A Meta-analysis of Randomized Clinical Trials.
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DOI：
10.1001/jamaneurol.2021.5578
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发表时间：
2022-04-01
期刊：
影响因子：
29
通讯作者：
Ovbiagele B
中科院分区：
文献类型：
--
作者：
Lee M;Cheng CY;Wu YL;Lee JD;Hsu CY;Ovbiagele B
与低密度脂蛋白胆固醇（LDL - C）降低幅度较小的治疗相比，基于他汀类药物的更强化的LDL - C降低疗法对二次卒中预防是否有益？
在这项纳入了11项随机临床试验、包含20163名卒中患者的荟萃分析中，更强化的LDL - C降低疗法组复发性卒中的风险为8%，而降低幅度较小的疗法组为9%，差异具有统计学意义。更强化的LDL - C降低疗法的益处可能仅见于有动脉粥样硬化证据的缺血性卒中患者。
这项研究表明，对于有动脉粥样硬化证据的缺血性卒中患者，基于他汀类药物的更强化的LDL - C降低疗法可能是必要的。
基于他汀类药物的强化降低低密度脂蛋白胆固醇（LDL - C）疗法在降低复发性卒中风险方面的益处和风险尚未确定。
对随机临床试验进行荟萃分析，以评估更强化与降低幅度较小的基于他汀类药物的LDL - C降低疗法与缺血性卒中患者预后的相关性。
检索了1970年1月1日至2021年7月31日期间的PubMed、Embase、Cochrane对照试验中心注册库和ClinicalTrials.gov。
这项荟萃分析纳入了比较更强化与降低幅度较小的基于他汀类药物的LDL - C降低疗法并记录卒中患者复发性卒中结果的随机临床试验。
采用系统综述和荟萃分析优先报告项目（PRISMA）报告指南提取数据以及评估数据质量和有效性。采用95%置信区间的相对风险（RR）来衡量更强化与降低幅度较小的LDL - C降低疗法与主要和次要结局的相关性。
主要结局是复发性卒中，次要结局是主要心血管事件和出血性卒中。
最终分析纳入了11项随机临床试验，涉及20163名卒中患者（13518名男性[67.0%]；平均[标准差]年龄为64.9[3.7]岁）。平均随访时间为4年（范围为1 - 6.1年）。汇总结果显示，与降低幅度较小的基于他汀类药物的LDL - C降低疗法相比，更强化的基于他汀类药物的LDL - C降低疗法与复发性卒中风险降低相关（绝对风险，8.1%对9.3%；RR，0.88；95%CI，0.80 - 0.96），并且这些LDL - C降低疗法的益处在不同的LDL - C降低策略之间没有差异（他汀类药物与无他汀类药物：RR，0.90；95%CI，0.81 - 1.01；更多他汀类药物或依折麦布与更少他汀类药物或依折麦布：RR，0.77；95%CI，0.62 - 0.96；前蛋白转化酶枯草杆菌蛋白酶/可馨型9抑制剂加他汀类药物与安慰剂加他汀类药物：RR，0.90；95%CI，0.71 - 1.15；交互作用P = 0.42）。与降低幅度较小的基于他汀类药物的LDL - C降低疗法相比，更强化的基于他汀类药物的LDL - C降低疗法与主要心血管事件风险降低相关，但出血性卒中风险增加。在所有患者都有动脉粥样硬化证据的试验中，与降低幅度较小的基于他汀类药物的LDL - C降低疗法相比，更强化的基于他汀类药物的LDL - C降低疗法与复发性卒中风险降低相关（RR，0.79；95%CI，0.69 - 0.91），但在大多数患者没有动脉粥样硬化证据的试验中则不相关（RR，0.95；95%CI，0.85 - 1.07；交互作用P = 0.04）。
这项研究表明，更强化的基于他汀类药物的LDL - C降低疗法在降低复发性卒中风险方面的益处和风险可能比降低幅度较小的基于他汀类药物的LDL - C降低疗法更有利，尤其是对于有动脉粥样硬化证据的患者。
这项对随机临床试验的荟萃分析评估了更强化与降低幅度较小的基于他汀类药物的低密度脂蛋白胆固醇降低疗法与缺血性卒中患者预后的相关性。
Are more intensive low-density lipoprotein cholesterol (LDL-C)–lowering statin-based therapies beneficial for secondary stroke prevention compared with less intensive LDL-C lowering? In this meta-analysis that included 11 randomized clinical trials comprising 20 163 patients with stroke, the risk of recurrent stroke was 8% with more intensive LDL-C lowering vs 9% with less intensive LDL-C lowering, a statistically significant difference. The benefits associated with more intensive LDL-C lowering might be found only in patients with ischemic stroke with evidence of atherosclerosis. This study suggests that more intensive LDL-C–lowering statin-based therapies might be warranted for patients with ischemic stroke with evidence of atherosclerosis. The benefits and risks associated with intensive low-density lipoprotein cholesterol (LDL-C)–lowering statin-based therapies to lessen the risk of recurrent stroke have not been established. To conduct a meta-analysis of randomized clinical trials to evaluate the association of more intensive vs less intensive LDL-C–lowering statin-based therapies with outcomes for patients with ischemic stroke. PubMed, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched from January 1, 1970, to July 31, 2021. This meta-analysis included randomized clinical trials that compared more intensive vs less intensive LDL-C–lowering statin-based therapies and recorded the outcome of recurrent stroke among patients with stroke. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline was used for abstracting data and assessing data quality and validity. Relative risk (RR) with 95% CI was used as a measure of the association of more intensive vs less intensive LDL-C lowering with primary and secondary outcomes. The primary outcome was recurrent stroke, and the secondary outcomes were major cardiovascular events and hemorrhagic stroke. The final analysis included 11 randomized clinical trials with 20 163 patients (13 518 men [67.0%]; mean [SD] age, 64.9 [3.7] years) with stroke. The mean follow-up was 4 years (range, 1-6.1 years). Pooled results showed that more intensive LDL-C–lowering statin-based therapies were associated with a reduced risk of recurrent stroke compared with less intensive LDL-C–lowering statin-based therapies (absolute risk, 8.1% vs 9.3%; RR, 0.88; 95% CI, 0.80-0.96) and that the benefit associated with these LDL-C–lowering therapies was not different among LDL-C–lowering strategies (statins vs no statins: RR, 0.90; 95% CI, 0.81-1.01; more statins or ezetimibe vs less statins or ezetimibe: RR, 0.77; 95% CI, 0.62-0.96; and proprotein convertase subtilisin/kexin type 9 inhibitors plus statins vs placebo plus statins: RR, 0.90; 95% CI, 0.71-1.15; P = .42 for interaction). More intensive LDL-C–lowering statin-based therapies were associated with a reduced risk of major cardiovascular events, but with an increased risk of hemorrhagic stroke, compared with less intensive LDL-C–lowering statin-based therapies. More intensive LDL-C–lowering statin-based therapies were associated with a reduced risk of recurrent stroke in trials with all patients having evidence of atherosclerosis (RR, 0.79; 95% CI, 0.69-0.91), but not in trials with most patients not having evidence of atherosclerosis (RR, 0.95; 95% CI, 0.85-1.07; P = .04 for interaction), compared with less intensive LDL-C–lowering statin-based therapies. This study suggests that the benefits and risks of more intensive LDL-C–lowering statin-based therapies for recurrent stroke risk reduction might be more favorable than the benefits and risks of less intensive LDL-C–lowering statin-based therapies, especially for patients with evidence of atherosclerosis. This meta-analysis of randomized clinical trials evaluates the association of more intensive vs less intensive low-density lipoprotein cholesterol–lowering statin-based therapies with outcomes for patients with ischemic stroke.
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