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年龄与他汀类药物治疗低密度脂蛋白胆固醇反应之间的关联:一项丹麦全国队列研究。

Association Between Age and Low-Density Lipoprotein Cholesterol Response to Statins : A Danish Nationwide Cohort Study.

作者信息

Corn Giulia, Melbye Mads, Hlatky Mark A, Wohlfahrt Jan, Lund Marie

机构信息

Department of Epidemiology Research, Statens Serum Institut, and Danish Cancer Society Research Center, Copenhagen, Denmark (G.C., J.W.).

Danish Cancer Society Research Center and Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark; K.G. Jebsen Center for Genetic Epidemiology, Norwegian University of Science and Technology, Trondheim, Norway; and Department of Genetics, Stanford University School of Medicine, Stanford, California (M.M.).

出版信息

Ann Intern Med. 2023 Aug;176(8):1017-1026. doi: 10.7326/M22-2643. Epub 2023 Aug 1.

Abstract

BACKGROUND

There is large patient-to-patient variability in the low-density lipoprotein cholesterol (LDL-C) response to statin treatment. The reduction in LDL-C may depend on the age of the patient treated-particularly in older adults, who have been substantially underrepresented in randomized controlled trials.

OBJECTIVE

To investigate the association between age and the LDL-C reduction by statins.

DESIGN

Nationwide, register-based cohort study.

SETTING

Denmark, 2008 to 2018.

PARTICIPANTS

82 958 simvastatin or atorvastatin initiators with LDL-C measurements before and during statin use.

MEASUREMENTS

Statin response, defined as percentage reduction in prestatin LDL-C level, and percentage reduction differences (PRDs) according to age and simvastatin or atorvastatin dose based on a longitudinal model for LDL-C.

RESULTS

Among 82 958 statin initiators, 10 388 (13%) were aged 75 years or older. With low- to moderate-intensity statins, initiators aged 75 years or older had greater mean LDL-C percentage reductions than initiators younger than 50 years-for example, 39.0% versus 33.8% for simvastatin, 20 mg, and 44.2% versus 40.2% for atorvastatin, 20 mg. The adjusted PRD for initiators aged 75 years compared with initiators aged 50 years was 2.62 percentage points. This association was consistent for primary prevention (2.54 percentage points) and secondary prevention (2.32 percentage points) but smaller for initiators of high-intensity statins (atorvastatin, 40 mg: 1.36 percentage points; atorvastatin, 80 mg: -0.58 percentage point).

LIMITATION

Use of administrative data, observational pre-post comparison with a moderately high proportion of missing data, lack of information on body mass index, and the mainly White study population may limit generalizability.

CONCLUSION

Low- to moderate-intensity statins were associated with a greater reduction in LDL-C levels in older persons than younger persons and may be more appealing as initial treatment in older adults who are at increased risk for adverse events.

PRIMARY FUNDING SOURCE

The Independent Research Fund Denmark, Brødrene Hartmanns Fond, and Fonden til Lægevidenskabens Fremme.

摘要

背景

低密度脂蛋白胆固醇(LDL-C)对他汀类药物治疗的反应在患者之间存在很大差异。LDL-C的降低可能取决于接受治疗患者的年龄,尤其是在老年人中,他们在随机对照试验中的代表性严重不足。

目的

研究年龄与他汀类药物降低LDL-C之间的关联。

设计

基于全国登记的队列研究。

地点

丹麦,2008年至2018年。

参与者

82958名开始使用辛伐他汀或阿托伐他汀的患者,在使用他汀类药物之前和期间进行了LDL-C测量。

测量指标

他汀类药物反应,定义为他汀类药物治疗前LDL-C水平的降低百分比,以及根据LDL-C纵向模型得出的按年龄和辛伐他汀或阿托伐他汀剂量划分的降低百分比差异(PRD)。

结果

在82958名开始使用他汀类药物的患者中,10388名(13%)年龄在75岁及以上。使用低至中等强度他汀类药物时,75岁及以上的开始使用者的平均LDL-C降低百分比高于50岁以下的开始使用者,例如,辛伐他汀20mg时分别为39.0%和33.8%,阿托伐他汀20mg时分别为44.2%和40.2%。75岁的开始使用者与50岁的开始使用者相比,调整后的PRD为2.62个百分点。这种关联在一级预防(2.54个百分点)和二级预防(2.32个百分点)中是一致的,但在高强度他汀类药物(阿托伐他汀40mg:1.36个百分点;阿托伐他汀80mg:-0.58个百分点)的开始使用者中较小。

局限性

使用行政数据、存在较高比例缺失数据的观察性前后比较、缺乏体重指数信息以及主要为白人的研究人群可能会限制研究结果的普遍性。

结论

低至中等强度他汀类药物与老年人LDL-C水平的降低幅度大于年轻人有关,对于不良事件风险增加的老年人,可能作为初始治疗更具吸引力。

主要资金来源

丹麦独立研究基金、布罗德雷纳·哈特曼斯基金会和医学发展基金会。

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