Intensive LDL cholesterol-lowering treatment beyond current recommendations for the prevention of major vascular events: a systematic review and meta-analysis of randomised trials including 327 037 participants.,The Lancet Diabetes & Endocrinology

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Intensive LDL cholesterol-lowering treatment beyond current recommendations for the prevention of major vascular events: a systematic review and meta-analysis of randomised trials including 327 037 participants.
The Lancet Diabetes & Endocrinology ( IF 44.0 ) Pub Date : 2020-01-01 , DOI: 10.1016/s2213-8587(19)30388-2
Nelson Wang ₁ , Jordan Fulcher ₂ , Nishan Abeysuriya ₃ , Laura Park ₄ , Shejil Kumar ₅ , Gian Luca Di Tanna ₆ , Ian Wilcox ₇ , Anthony Keech ₈ , Anthony Rodgers ₉ , Sean Lal ₇

Affiliation

University of Sydney, Sydney, NSW, Australia; Department of Cardiology, Royal Prince Alfred Hospital, Sydney, NSW, Australia; The George Institute, Sydney, NSW, Australia; University of New South Wales, Sydney, NSW, Australia.
NHMRC Clinical Trials Centre, University of Sydney, Sydney, NSW, Australia; Department of Cardiology, Royal Prince Alfred Hospital, Sydney, NSW, Australia; Central Sydney Cardiology, Sydney, NSW, Australia.
Princess Alexandra Hospital, Brisbane, QLD, Australia.
University of Sydney, Sydney, NSW, Australia.
Royal North Shore Hospital, Sydney, NSW, Australia.
The George Institute, Sydney, NSW, Australia.
University of Sydney, Sydney, NSW, Australia; Department of Cardiology, Royal Prince Alfred Hospital, Sydney, NSW, Australia; Central Sydney Cardiology, Sydney, NSW, Australia.
NHMRC Clinical Trials Centre, University of Sydney, Sydney, NSW, Australia; University of Sydney, Sydney, NSW, Australia; Department of Cardiology, Royal Prince Alfred Hospital, Sydney, NSW, Australia.
The George Institute, Sydney, NSW, Australia; University of New South Wales, Sydney, NSW, Australia.

BACKGROUND The benefits of LDL cholesterol-lowering treatment for the prevention of atherosclerotic cardiovascular disease are well established. However, the extent to which these effects differ by baseline LDL cholesterol, atherosclerotic cardiovascular disease risk, and the presence of comorbidities remains uncertain. METHODS We did a systematic literature search (MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials, from inception up to June 15, 2019) for randomised controlled trials of statins, ezetimibe, and proprotein convertase subtilisin/kexin type 9 inhibitors with at least 1000 patient-years of follow-up. Random-effects meta-analysis and meta-regressions were done to assess for risk of major vascular events (a composite of cardiovascular mortality, non-fatal myocardial infarction, non-fatal ischaemic stroke, or coronary revascularisation) per 1 mmol/L (38·7 mg/dL) reduction in LDL cholesterol concentrations. FINDINGS 327 037 patients from 52 studies were included in the meta-analysis. Each 1 mmol/L reduction in LDL cholesterol was associated with a 19% relative risk (RR) reduction for major vascular events (RR 0·81 [95% CI 0·78-0·84]; p<0·0001). Similar reductions (per 1 mmol/L reduction in LDL cholesterol) were found in trials with participants with LDL cholesterol 2·60 mmol/L or lower, 2·61-3·40 mmol/L, 3·41-4·10 mmol/L, and more than 4·1 mmol/L (p=0·232 for interaction); and in a subgroup of patients who all had a baseline LDL cholesterol less than 2·07 mmol/L (80 mg/dL; RR 0·83 [95% CI 0·75-0·92]; p=0·001). We found greater RR reductions in patients at lower 10-year atherosclerotic cardiovascular disease risk (change in RR per 10% lower 10-year atherosclerotic cardiovascular disease 0·97 [95% CI 0·95-0·98]; p<0·0001) and in patients at younger age across a mean age of 50-75 years (change in RR per 10 years younger age 0·92 [0·83-0·97]; p=0·015). We found no difference in RR reduction for participants with or without diabetes (p=0·878 for interaction) and chronic kidney disease (p=0·934 for interaction). INTERPRETATION For each 1 mmol/L LDL cholesterol lowering, the risk reduction of major vascular events is independent of the starting LDL cholesterol or the presence of diabetes or chronic kidney disease. Patients at lower cardiovascular risk and younger age might have a similar relative reduction in risk with LDL-cholesterol lowering therapies and future studies should investigate the potential benefits of earlier intervention. FUNDING None.

中文翻译：

降低LDL胆固醇的强化治疗超出了当前预防主要血管事件的建议：对包括327,037名受试者的随机试验进行系统的回顾和荟萃分析。

背景技术降低LDL胆固醇的治疗对预防动脉粥样硬化性心血管疾病的益处已得到充分确立。然而，这些影响在多大程度上因基线低密度脂蛋白胆固醇，动脉粥样硬化性心血管疾病的风险以及合并症的存在而异。方法我们进行了系统的文献检索（MEDLINE，Embase和对照试验的Cochrane中央登记册，从成立至2019年6月15日），用于他汀类药物，依泽替米贝和前蛋白转化酶枯草杆菌蛋白酶/ kexin 9型抑制剂与的随机对照试验。至少1000个患者-年的随访。进行了随机效应荟萃分析和荟萃回归，以评估主要血管事件的风险（心血管疾病死亡率，非致命性心肌梗死，非致命性缺血性卒中，或LDL胆固醇浓度每降低1 mmol / L（38·7 mg / dL）进行冠状动脉血运重建。结果来自52个研究的327037患者被纳入荟萃分析。LDL胆固醇每降低1 mmol / L，主要血管事件的相对危险度（RR）降低19％（RR 0·81 [95％CI 0·78-0·84]； p <0·0001）。在LDL胆固醇为2·60 mmol / L或更低，2·61-3·40 mmol / L，3·41-4·10 mmol的参与者的试验中，发现类似的降低（每降低1 mmol / L LDL胆固醇） / L，且大于4·1 mmol / L（相互作用时p = 0·232）；在所有基线LDL胆固醇低于2·07 mmol / L（80 mg / dL； RR 0·83 [95％CI 0·75-0·92]； p = 0·001）的患者亚组中。我们发现较低的10年动脉粥样硬化性心血管疾病风险患者的RR降低更大（每降低10％的10年动脉粥样硬化性心血管疾病的RR变化0·97 [95％CI 0·95-0·98]； p <0· 0001）以及平均年龄在50-75岁之间的更年轻患者（每10岁以下RR的变化0·92 [0·83-0·97]； p = 0·015）。我们发现患有或不患有糖尿病的受试者（相互作用的p = 0·878）和慢性肾脏病（相互作用的p = 0·934）的RR降低没有差异。解释每降低1 mmol / L LDL胆固醇，主要血管事件的风险降低与起始LDL胆固醇或糖尿病或慢性肾脏疾病的存在无关。心血管疾病风险较低且年龄较小的患者，通过降低LDL-胆固醇的治疗可能相对降低风险，未来的研究应研究早期干预的潜在益处。资金无。

更新日期：2019-12-18

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