他汀可治疗糖尿病患者动脉粥样硬化

旧金山——在美国心脏病学会(ACC)2013年会上公布的SATURN研究事后亚组分析显示，在使用高强度他汀类药物治疗症状性冠状动脉疾病的糖尿病患者和非糖尿病患者中，动脉粥样硬化斑块的退化程度相似。

在SATURN研究中，患者接受两种他汀类药物之一，即40 mg/d瑞舒伐他汀或80 mg/d阿托伐他汀治疗2年，并通过连续血管内超声评估疾病退化情况。两个药物组的PAV降幅相似，瑞舒伐他汀组的TAV降幅大于阿托伐他汀(N. Engl. J. Med. 2011;365:2078-87)。既往研究采用血管内超声评估发现，LDL水平的明显降低可导致冠状动脉粥样硬化斑块明显退化，但尚不清楚这种现象是否在糖尿病患者和非糖尿病患者中均存在。因此，克里夫兰医学中心的Brian Stegman博士及其同事对SATURN队列进行了重新分组和分析。

这项分析纳入1,039例患者，其中159例为糖尿病患者，880例为非糖尿病患者。主要终点为动脉粥样硬化斑块体积百分比(PAV)，定义为动脉粥样硬化斑块占单个血管体积的百分比。次要终点为总动脉粥样硬化斑块体积(TAV)。

结果显示，糖尿病组和非糖尿病组的PAV相对于基线水平分别平均降低1.04%和1.21%，两组的降幅均显著。糖尿病组和非糖尿病组的TAV相对于基线水平分别降低5.62 mm³和7.29 mm³，两组的降幅也具有显著性。

高强度他汀类药物治疗使两组患者的LDL出现相似程度的明显降低：糖尿病组降低52 mg/dl，非糖尿病组降低55 mg/dl。糖尿病组和非糖尿病组的HDL分别增加3 mg/dl和5 mg/dl，组间差异显著。糖尿病组和非糖尿病组的总胆固醇分别降低52 mg/dl和54 mg/dl，甘油三酯水平分别降低13 mg/dl和12 mg/dl，组间差异均不显著。

线性回归模型显示，在糖尿病组和非糖尿病组中，治疗后LDL越低，动脉粥样硬化斑块的退化越大。通过测定管腔体积和外弹性膜体积的变化发现，2年内两组的管腔体积的保存程度相似。

该分析的局限性在于为事后分析，并且两组患者的数量和基线特征存在差异。与非糖尿病组相比，糖尿病组患者的年龄明显更大，平均体重指数更高，女性比例更大，并且具有高血压史的比例也更高。两组的基线血脂水平存在显著差异，糖尿病组的总胆固醇、LDL和HDL水平更低，甘油三酯水平更高。两组的血管内超声检查结果也存在显著差异，糖尿病组的PAV和TAV大于非糖尿病组。此外，该分析的另一局限是采用PAV和TAV作为临床终点的替代指标，不过既往血管内超声研究显示，PAV越大和PAV进展越大，主要不良心血管事件的风险越高。

Stegman博士声明无相关经济利益冲突，其他研究者声明与多家销售他汀类药物的医药公司存在利益关系。

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By: SHERRY BOSCHERT, Cardiology News Digital Network

SAN FRANCISCO – Atheromas regressed to similar degrees in patients with or without diabetes on high-intensity statin therapy for symptomatic coronary artery disease, a post hoc subgroup analysis of 1,039 patients found.

The primary endpoint, percent atheroma volume (PAV), decreased by a mean of 1.04% in 159 diabetic patients and by 1.21% in 880 nondiabetic patients compared with baseline – significant drops in both groups, Dr. Brian Stegman and his associates reported. PAV is the percentage of a single vessel’s volume occupied by atheroma.

The total atheroma volume (TAV), a secondary endpoint, decreased compared with baseline by 5.62 mm3 in the diabetic group and by 7.29 mm3 in the nondiabetic group, both of which also were significant changes, he said at the annual meeting of the American College of Cardiology.

Data came from the SATURN (Study of Coronary Atheroma by Intravascular Ultrasound: Effect of Rosuvastatin Versus Atorvastatin) trial, which compared intensive therapy with one of the two statin drugs in patients who underwent serial intravascular ultrasonography to assess disease regression. Patients were treated with either 40 mg/day rosuvastatin or 80 mg/day atorvastatin for 2 years. The two drug groups showed similar reductions in PAV, with a greater reduction in TAV using rosuvastatin (N. Engl. J. Med. 2011;365:2078-87).

Previous studies using have shown that aggressive reductions in LDL levels lead to significant regression in coronary atheromas as measured by intravascular ultrasound, but it has not been clear whether this is true in patients with diabetes as well as those without, said Dr. Stegman of the Cleveland Clinic Foundation.

The current analysis regrouped the SATURN cohort by diabetes status. High-intensity statin therapy produced substantial reductions in LDL in both groups, to a similar degree: a 52-mg/dL drop in diabetics and a 55-mg/dL decrease in nondiabetics. HDL levels increased by 3 mg/dL in diabetics and 5 mg/dL in nondiabetics, a significant difference between groups. Total cholesterol decreased 52 mg/dL in diabetics and 54 mg/dL in nondiabetics, and triglyceride levels decreased 13 mg/dL in diabetics and 12 mg/dL in nondiabetics, measures that were not significantly different between groups.

In both diabetics and nondiabetics, the lower the LDL on treatment, the greater the regression of atheroma, according to a linear regression model constructed by the investigators.

The changes in PAV and TAV in both groups showed that "with high-intensity statin therapy, we saw equal regression of atheroma in diabetics compared with nondiabetics," Dr. Stegman said. Lumen volumes were preserved over the 2-year period to a similar degree in both groups, as measured by change in lumen volume and external elastic membrane volume.

The findings differ from previous results in a pooled analysis of five trials involving intravascular ultrasound measurements of atherosclerosis progression in 2,237 patients, 416 of whom had diabetes, he noted. In that analysis, PAV increased by 0.05% in diabetics and by 0.6% in nondiabetics, compared with decreases of 1.21% and 1.04%, respectively, in the current analysis. The TAV decreased by 2.7 mm3 in diabetics and 0.6 mm3 in nondiabetics, much less than the 7.29-mm3 and 5.62-mm3 decreases, respectively, in the current analysis (J. Am. Coll. Cardiol. 2008;52:255-62).

The different outcomes in the two analyses may be due to less aggressive treatment in the trials pooled in the 2008 analysis, which did not decrease LDL levels as much as the high-intensity regimens in the SATURN trial. "I think our current study indicates that diabetic patients require fairly aggressive lipid therapy to get the same results as in nondiabetic patients," Dr. Stegman said.

Separate, previous trials using intravascular ultrasound have shown that high-dose statin therapy is more effective than moderate- or low dose regimens to halt progression of atherosclerosis, he added.

The analysis is limited by its post hoc nature, differing patient numbers in each group, and differences in baseline characteristics. Patients in the diabetic group were significantly older, with a higher mean body mass index, and more likely to be female and to have a history of hypertension compared with nondiabetics. Baseline lipid levels were significantly different between groups, with lower total cholesterol, LDL, and HDL levels and higher triglyceride levels in patients with diabetes. Intravascular ultrasound measurements also differed significantly, with greater PAV and TAV in the diabetic group.

The PAV and TAV endpoints were surrogate measures of clinical outcomes, another limitation of the analysis, but previous studies with intravascular ultrasound have reported that greater PAV and greater progression of PAV are associated with an increased risk of major adverse cardiovascular events, he said.

Dr. Stegman reported having no relevant financial disclosures. Some of his associates in the study reported financial associations with multiple pharmaceutical companies, several of which market statins.