阿托伐他汀治疗患者新发糖尿病的预测因素：3 项大型随机临床试验的结果。

Predictors of new-onset diabetes in patients treated with atorvastatin: results from 3 large randomized clinical trials.

机构信息

Division of Cardiology, San Francisco General Hospital, and University of California at San Francisco, San Francisco, California 94114, USA.

出版信息

J Am Coll Cardiol. 2011 Apr 5;57(14):1535-45. doi: 10.1016/j.jacc.2010.10.047.

DOI:10.1016/j.jacc.2010.10.047

PMID:21453832

Abstract

OBJECTIVES

We sought to examine the incidence and clinical predictors of new-onset type 2 diabetes mellitus (T2DM) within 3 large randomized trials with atorvastatin.

BACKGROUND

Statin therapy might modestly increase the risk of new-onset T2DM.

METHODS

We used a standard definition of diabetes and excluded patients with prevalent diabetes at baseline. We identified baseline predictors of new-onset T2DM and compared the event rates in patients with and without new-onset T2DM.

RESULTS

In the TNT (Treating to New Targets) trial, 351 of 3,798 patients randomized to 80 mg of atorvastatin and 308 of 3,797 randomized to 10 mg developed new-onset T2DM (9.24% vs. 8.11%, adjusted hazard ratio [HR]: 1.10, 95% confidence interval [CI]: 0.94 to 1.29, p = 0.226). In the IDEAL (Incremental Decrease in End Points Through Aggressive Lipid Lowering) trial, 239 of 3,737 patients randomized to atorvastatin 80 mg/day and 208 of 3,724 patients randomized to simvastatin 20 mg/day developed new-onset T2DM (6.40% vs. 5.59%, adjusted HR: 1.19, 95% CI: 0.98 to 1.43, p = 0.072). In the SPARCL (Stroke Prevention by Aggressive Reduction in Cholesterol Levels) trial, new-onset T2DM developed in 166 of 1,905 patients randomized to atorvastatin 80 mg/day and in 115 of 1,898 patients in the placebo group (8.71% vs. 6.06%, adjusted HR: 1.37, 95% CI: 1.08 to 1.75, p = 0.011). In each of the 3 trials, baseline fasting blood glucose, body mass index, hypertension, and fasting triglycerides were independent predictors of new-onset T2DM. Across the 3 trials, major cardiovascular events occurred in 11.3% of patients with and 10.8% of patients without new-onset T2DM (adjusted HR: 1.02, 95% CI: 0.77 to 1.35, p = 0.69).

CONCLUSIONS

High-dose atorvastatin treatment compared with placebo in the SPARCL trial is associated with a slightly increased risk of new-onset T2DM. Baseline fasting glucose level and features of the metabolic syndrome are predictive of new-onset T2DM across the 3 trials.

摘要

目的

我们旨在研究 3 项阿托伐他汀随机临床试验中，新诊断 2 型糖尿病（T2DM）的发生率和临床预测因素。

背景

他汀类药物治疗可能会适度增加新发 T2DM 的风险。

方法

我们使用糖尿病的标准定义，并排除基线时患有糖尿病的患者。我们确定了新发 T2DM 的基线预测因素，并比较了新发 T2DM患者和无新发 T2DM患者的事件发生率。

结果

在 TNT（针对新目标的治疗）试验中，351 例被随机分配至阿托伐他汀 80mg 的 3798 例患者和 308 例被随机分配至阿托伐他汀 10mg 的 3797 例患者中出现新发 T2DM（9.24% vs. 8.11%，调整后的危险比[HR]：1.10，95%置信区间[CI]：0.94 至 1.29，p=0.226）。在 IDEAL（通过积极降低血脂水平来增加终点获益）试验中，239 例被随机分配至阿托伐他汀 80mg/天的 3737 例患者和 208 例被随机分配至辛伐他汀 20mg/天的 3724 例患者中出现新发 T2DM（6.40% vs. 5.59%，调整后的 HR：1.19，95%CI：0.98 至 1.43，p=0.072）。在 SPARCL（通过积极降低胆固醇水平预防卒中）试验中，1905 例被随机分配至阿托伐他汀 80mg/天的患者中有 166 例和 1898 例被随机分配至安慰剂的患者中有 115 例出现新发 T2DM（8.71% vs. 6.06%，调整后的 HR：1.37，95%CI：1.08 至 1.75，p=0.011）。在这 3 项试验中的每一项中，基线空腹血糖、体重指数、高血压和空腹甘油三酯都是新发 T2DM 的独立预测因素。在这 3 项试验中，新发 T2DM患者和无新发 T2DM患者的主要心血管事件发生率分别为 11.3%和 10.8%（调整后的 HR：1.02，95%CI：0.77 至 1.35，p=0.69）。