Efficacy and safety of lowering LDL cholesterol in older patients: a systematic review and meta-analysis of randomised controlled trials.
Efficacy and safety of lowering LDL cholesterol in older patients: a systematic review and meta-analysis of randomised controlled trials.
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DOI：
10.1016/s0140-6736(20)32332-1
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发表时间：
2020-11-21
期刊：
影响因子：
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通讯作者：
Sabatine MS
中科院分区：
文献类型：
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作者：
Gencer B;Marston NA;Im K;Cannon CP;Sever P;Keech A;Braunwald E;Giugliano RP;Sabatine MS
老年患者LDL胆固醇降低治疗的临床获益仍有争议。我们的目的是总结老年患者LDL胆固醇降低治疗的证据。在这项系统性综述和荟萃分析中，我们检索了MEDLINE和Embase中2015年3月1日至2020年8月14日期间发表的文章，没有任何语言限制。我们纳入了2018年美国心脏病学会和美国心脏协会指南推荐的LDL降胆固醇药物的心血管结局的随机对照试验，中位随访时间至少为2年，数据来自老年患者（年龄≥75岁）。我们排除了专门招募心力衰竭或透析参与者的试验，因为指南不建议对没有其他适应症的此类患者进行降脂治疗。我们使用标准化数据表提取老年患者的数据，用于汇总研究水平数据。我们对LDL胆固醇每降低1 mmol/L发生主要血管事件（心血管死亡、心肌梗死或其他急性冠脉综合征、卒中或冠状动脉血运重建的复合事件）的风险比（RR）进行了荟萃分析。来自6篇文章的数据被纳入系统综述和荟萃分析，其中包括来自胆固醇治疗试验者协作荟萃分析的24项试验加上5项单独试验。在来自29项试验的244090例患者中，21492例（8.8%）年龄至少为75岁，其中11750例（54.7%）来自他汀类药物试验，6209例（28.9%）来自依折麦布试验，3533例（16.4%）来自PCSK 9抑制剂试验。中位随访时间为2.2年至6.0年。在老年患者中，降低LDL胆固醇显著降低主要血管事件的风险（n=3519），LDL胆固醇每降低1 mmol/L降低26%（RR 0.74 [95% CI 0.61 - 0.89]; p= 0.0019），与年龄小于75岁患者的风险降低无统计学显著差异（0·85 [0·78-0·92]; pinteraction=0·37）。在老年患者中，他汀类药物治疗（0.82 [0.73 - 0.91]）和非他汀类药物治疗（0.67 [0.47 - 0.95]; pinteraction= 0.64）的RR无统计学差异。在老年患者中，观察到复合终点的每一个组成部分都有降低LDL胆固醇的益处，包括心血管死亡（0·85 [0·74-0·98]）、心肌梗死（0·80 [0·71-0·90]）、卒中（0·73 [0·61-0·87]）和冠状动脉血运重建（0·80 [0·66-0·96]）。在75岁及以上的患者中，降脂在减少心血管事件方面与75岁以下的患者一样有效。这些结果应加强指南建议使用降脂治疗，包括非他汀类药物治疗，在老年患者。没有。
The clinical benefit of LDL cholesterol lowering treatment in older patients remains debated. We aimed to summarise the evidence of LDL cholesterol lowering therapies in older patients. In this systematic review and meta-analysis, we searched MEDLINE and Embase for articles published between March 1, 2015, and Aug 14, 2020, without any language restrictions. We included randomised controlled trials of cardiovascular outcomes of an LDL cholesterol-lowering drug recommended by the 2018 American College of Cardiology and American Heart Association guidelines, with a median follow-up of at least 2 years and data on older patients (aged ≥75 years). We excluded trials that exclusively enrolled participants with heart failure or on dialysis because guidelines do not recommend lipid-lowering therapy in such patients who do not have another indication. We extracted data for older patients using a standardised data form for aggregated study-level data. We meta-analysed the risk ratio (RR) for major vascular events (a composite of cardiovascular death, myocardial infarction or other acute coronary syndrome, stroke, or coronary revascularisation) per 1 mmol/L reduction in LDL cholesterol. Data from six articles were included in the systematic review and meta-analysis, which included 24 trials from the Cholesterol Treatment Trialists’ Collaboration meta-analysis plus five individual trials. Among 244 090 patients from 29 trials, 21 492 (8·8%) were aged at least 75 years, of whom 11 750 (54·7%) were from statin trials, 6209 (28·9%) from ezetimibe trials, and 3533 (16·4%) from PCSK9 inhibitor trials. Median follow-up ranged from 2·2 years to 6·0 years. LDL cholesterol lowering significantly reduced the risk of major vascular events (n=3519) in older patients by 26% per 1 mmol/L reduction in LDL cholesterol (RR 0·74 [95% CI 0·61–0·89]; p=0·0019), with no statistically significant difference with the risk reduction in patients younger than 75 years (0·85 [0·78–0·92]; pinteraction=0·37). Among older patients, RRs were not statistically different for statin (0·82 [0·73–0·91]) and non-statin treatment (0·67 [0·47–0·95]; pinteraction=0·64). The benefit of LDL cholesterol lowering in older patients was observed for each component of the composite, including cardiovascular death (0·85 [0·74–0·98]), myocardial infarction (0·80 [0·71–0·90]), stroke (0·73 [0·61–0·87]), and coronary revascularisation (0·80 [0·66–0·96]). In patients aged 75 years and older, lipid lowering was as effective in reducing cardiovascular events as it was in patients younger than 75 years. These results should strengthen guideline recommendations for the use of lipid-lowering therapies, including non-statin treatment, in older patients. None.