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阿托伐他汀对糖尿病患者血糖进展的影响:来自糖尿病协作阿托伐他汀试验(CARDS)的分析。

Effect of atorvastatin on glycaemia progression in patients with diabetes: an analysis from the Collaborative Atorvastatin in Diabetes Trial (CARDS).

作者信息

Livingstone Shona J, Looker Helen C, Akbar Tahira, Betteridge D John, Durrington Paul N, Hitman Graham A, Neil H Andrew W, Fuller John H, Colhoun Helen M

机构信息

Diabetes Epidemiology Unit, Division of Population Health Sciences, University of Dundee, The Mackenzie Building, Kirsty Semple Way, Dundee, DD2 4BF, Scotland, UK.

Department of Endocrinology and Diabetes, University College Hospital, London, UK.

出版信息

Diabetologia. 2016 Feb;59(2):299-306. doi: 10.1007/s00125-015-3802-6. Epub 2015 Nov 17.

Abstract

AIMS/HYPOTHESIS: In an individual-level analysis we examined the effect of atorvastatin on glycaemia progression in type 2 diabetes and whether glycaemia effects reduce the prevention of cardiovascular disease (CVD) with atorvastatin.

METHODS

The study population comprised 2,739 people taking part in the Collaborative Atorvastatin Diabetes Study (CARDS) who were randomised to receive atorvastatin 10 mg or placebo and who had post-randomisation HbA1c data. This secondary analysis used Cox regression to estimate the effect of atorvastatin on glycaemia progression, defined as an increase in HbA1c of ≥ 0.5% (5.5 mmol/mol) or intensification of diabetes therapy. Mixed models were used to estimate the effect of atorvastatin on HbA1c as a continuous endpoint.

RESULTS

Glycaemia progression occurred in 73.6% of participants allocated placebo and 78.1% of those allocated atorvastatin (HR 1.18 [95% CI 1.08, 1.29], p < 0.001) by the end of follow-up. The HR was 1.22 (95% CI 1.19, 1.35) in men and 1.11 (95% CI 0.95, 1.29) in women (p = 0.098 for the sex interaction). A similar effect was seen in on-treatment analyses: HR 1.20 (95% CI 1.07, 1.35), p = 0.001. The net mean treatment effect on HbA1c was 0.14% (95% CI 0.08, 0.21) (1.5 mmol/mol). The effect did not increase through time. Diabetes treatment intensification alone did not differ with statin allocation. Neither baseline nor 1-year-attained HbA1c predicted subsequent CVD, and the atorvastatin effect on CVD did not vary by HbA1c change (interaction p value 0.229).

CONCLUSIONS/INTERPRETATION: The effect of atorvastatin 10 mg on glycaemia progression among those with diabetes is statistically significant but very small, is not significantly different between sexes, does not increase with duration of statin and does not have an impact on the magnitude of CVD risk reduction with atorvastatin.

摘要

目的/假设:在个体水平分析中,我们研究了阿托伐他汀对2型糖尿病患者血糖进展的影响,以及血糖影响是否会降低阿托伐他汀对心血管疾病(CVD)的预防作用。

方法

研究人群包括2739名参与阿托伐他汀糖尿病协作研究(CARDS)的患者,他们被随机分配接受10毫克阿托伐他汀或安慰剂,并且有随机分组后的糖化血红蛋白(HbA1c)数据。这项二次分析使用Cox回归来估计阿托伐他汀对血糖进展的影响,血糖进展定义为HbA1c升高≥0.5%(5.5 mmol/mol)或糖尿病治疗强化。混合模型用于估计阿托伐他汀对HbA1c作为连续终点的影响。

结果

随访结束时,分配到安慰剂组的参与者中有73.6%出现血糖进展,分配到阿托伐他汀组的参与者中有78.1%出现血糖进展(风险比[HR] 1.18 [95%置信区间(CI)1.08, 1.29],p < 0.001)。男性的HR为1.22(95% CI 1.19, 1.35),女性为1.11(95% CI 0.95, 1.29)(性别交互作用p = 0.098)。在治疗期间分析中观察到类似的效果:HR 1.20(95% CI 1.07, 1.35),p = 0.001。阿托伐他汀对HbA1c的净平均治疗效果为0.14%(95% CI 0.08, 0.21)(1.5 mmol/mol)。该效果不会随时间增加。单纯糖尿病治疗强化在他汀类药物分配方面没有差异。基线或1年时达到的HbA1c均不能预测随后的CVD,并且阿托伐他汀对CVD的影响不会因HbA1c变化而不同(交互作用p值为0.229)。

结论/解读:10毫克阿托伐他汀对糖尿病患者血糖进展的影响具有统计学意义,但非常小,在性别之间无显著差异,不会随他汀类药物使用时间增加,并且对阿托伐他汀降低CVD风险的幅度没有影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1cf4/4705133/c6f0bc58b657/125_2015_3802_Fig1_HTML.jpg

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