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不同类型和强度的他汀类药物对糖尿病患者心血管高危人群血脂的影响分析
作者:小柯机器人 发布时间:2022/3/27 19:43:19

英国曼彻斯特大学Alexander Hodkinson团队比较分析了他汀类药物对糖尿病和心血管疾病高危人群非高密度脂蛋白胆固醇的疗效。这一研究成果于2022年3月24日发表在《英国医学杂志》上。

为了比较糖尿病患者接受不同强度的他汀类药物治疗以预防心血管疾病对非高密度脂蛋白胆固醇(non-HDL-C)水平的影响,研究组在Medline、Cochrane对照试验中心登记册和Embase等大型数据库中检索从建库至2021年12月1日的相关文献,筛选出比较成人1型或2型糖尿病患者服用不同类型和强度的他汀类药物(包括安慰剂)的随机对照试验,进行系统回顾和网络荟萃分析。

主要结局为通过测量总胆固醇和高密度脂蛋白胆固醇计算得出的非高密度脂蛋白胆固醇水平的变化。次要结局是低密度脂蛋白胆固醇(LDL-C)和总胆固醇水平的变化,三点重大心血管事件(非致命性中风、非致命性心肌梗死和与心血管疾病相关的死亡),以及因不良事件而停药。

一项针对他汀类药物强度(低、中、高)和随机效应的贝叶斯网络荟萃分析通过平均差异和95%置信区间评估了非高密度脂蛋白胆固醇的治疗效果。对重大心血管事件风险较高的患者与低风险或中等风险的患者进行亚组分析比较。应用网络荟萃分析(CINeMA)框架来评估证据的确定性。

在涉及20193名成年人的42项随机对照试验中,共有11698人被纳入荟萃分析。与安慰剂相比,高强度(2.31 mmol/L)和中等强度(2.27)的瑞舒伐他汀,以及高强度的辛伐他汀(2.26)和阿托伐他汀(2.20)的非高密度脂蛋白胆固醇水平下降幅度最大。

任何强度的阿托伐他汀和辛伐他汀以及低强度的普伐他汀也能有效降低非高密度脂蛋白胆固醇水平。在4670名有较大心血管事件风险的患者中,高强度的阿托伐他汀显示出非高密度脂蛋白胆固醇水平的最大降低(1.98)。

高强度辛伐他汀(1.93)和瑞舒伐他汀(1.76)是降低LDL-C的最有效治疗方案。与安慰剂相比,中等强度阿托伐他汀的非致命性心肌梗死率显著降低,相对风险为0.57。在停药、非致命性中风和心血管死亡方面未发现显著差异。

该网络荟萃分析表明,中高强度剂量的瑞舒伐他汀以及高强度剂量的辛伐他汀和阿托伐他汀在中度降低糖尿病患者非HDL-C水平方面最有效。考虑到以降低非HDL-C水平作为主要目标时,预测心血管疾病的准确性可能会提高,这些发现为糖尿病患者降低非HDL-C最有效的他汀类药物类型和强度提供了指导。

附:英文原文

Title: Comparative effectiveness of statins on non-high density lipoprotein cholesterol in people with diabetes and at risk of cardiovascular disease: systematic review and network meta-analysis

Author: Alexander Hodkinson, Dialechti Tsimpida, Evangelos Kontopantelis, Martin K Rutter, Mamas A Mamas, Maria Panagioti

Issue&Volume: 2022/03/24

Abstract:

Objective To compare the efficacy of different statin treatments by intensity on levels of non-high density lipoprotein cholesterol (non-HDL-C) for the prevention of cardiovascular disease in people with diabetes.

Design Systematic review and network meta-analysis.

Data sources Medline, Cochrane Central Register of Controlled Trials, and Embase from inception to 1 December 2021.

Review methods Randomised controlled trials comparing different types and intensities of statins, including placebo, in adults with type 1 or type 2 diabetes mellitus were included. The primary outcome was changes in levels of non-HDL-C, calculated from measures of total cholesterol and HDL-C. Secondary outcomes were changes in levels of low density lipoprotein cholesterol (LDL-C) and total cholesterol, three point major cardiovascular events (non-fatal stroke, non-fatal myocardial infarction, and death related to cardiovascular disease), and discontinuations because of adverse events. A bayesian network meta-analysis of statin intensity (low, moderate, or high) with random effects evaluated the treatment effect on non-HDL-C by mean differences and 95% credible intervals. Subgroup analysis of patients at greater risk of major cardiovascular events was compared with patients at low or moderate risk. The confidence in network meta-analysis (CINeMA) framework was applied to determine the certainty of evidence.

Results In 42 randomised controlled trials involving 20193 adults, 11698 were included in the meta-analysis. Compared with placebo, the greatest reductions in levels of non-HDL-C were seen with rosuvastatin at high (2.31 mmol/L, 95% credible interval 3.39 to 1.21) and moderate (2.27, 3.00 to 1.49) intensities, and simvastatin (2.26, 2.99 to 1.51) and atorvastatin (2.20, 2.69 to 1.70) at high intensity. Atorvastatin and simvastatin at any intensity and pravastatin at low intensity were also effective in reducing levels of non-HDL-C. In 4670 patients at greater risk of a major cardiovascular events, atorvastatin at high intensity showed the largest reduction in levels of non-HDL-C (1.98, 4.16 to 0.26, surface under the cumulative ranking curve 64%). Simvastatin (1.93, 2.63 to 1.21) and rosuvastatin (1.76, 2.37 to 1.15) at high intensity were the most effective treatment options for reducing LDL-C. Significant reductions in non-fatal myocardial infarction were found for atorvastatin at moderate intensity compared with placebo (relative risk=0.57, confidence interval 0.43 to 0.76, n=4 studies). No significant differences were found for discontinuations, non-fatal stroke, and cardiovascular deaths.

Conclusions This network meta-analysis indicated that rosuvastatin, at moderate and high intensity doses, and simvastatin and atorvastatin, at high intensity doses, were most effective at moderately reducing levels of non-HDL-C in patients with diabetes. Given the potential improvement in accuracy in predicting cardiovascular disease when reduction in levels of non-HDL-C is used as the primary target, these findings provide guidance on which statin types and intensities are most effective by reducing non-HDL-C in patients with diabetes.

DOI: 10.1136/bmj-2021-067731

Source: https://www.bmj.com/content/376/bmj-2021-067731

期刊信息

BMJ-British Medical Journal:《英国医学杂志》,创刊于1840年。隶属于BMJ出版集团,最新IF:27.604
官方网址:http://www.bmj.com/
投稿链接:https://mc.manuscriptcentral.com/bmj