Department of Biostatistics, School of Public Health, the University of Tokyo, Tokyo, Japan.
Geriatr Gerontol Int. 2012 Apr;12 Suppl 1:88-102. doi: 10.1111/j.1447-0594.2011.00816.x.
To assess the preventive effect of atorvastatin on cardiovascular disease and on diabetes-related events in elderly type 2 diabetic patients enrolled in the Japanese Elderly Diabetes Intervention Trial (J-EDIT).
Data were obtained from 1173 patients aged 65-84 years who were enrolled in the J-EDIT. Patients were followed prospectively for 6 years to determine the effects of atorvastatin on serum cholesterol levels, and cardiovascular and diabetes-related events. Because the study protocol allowed atorvastatin to be prescribed according to the clinical needs of each patient, we regarded the J-EDIT data as if they came from a cohort study. We adjusted for clinical characteristics during the study as time-dependent confounders using two methods, inverse-probability-of-treatment (IPT) weighting and g-estimation method.
The total follow-up period was 5310.8 person-years (5.7 years of median follow up), during which 202 patients received atorvastatin treatment. Atorvastatin was associated with moderate reductions in cholesterol levels: 24.2 mg/dL for total cholesterol, 22.9 mg/dL for low-density lipoprotein (LDL) cholesterol and 24.3 mg/dL for non-high-density lipoprotein cholesterol at the first post-treatment year. As a result, the proportion of patients who achieved targeted levels of LDL cholesterol clearly increased after atorvastatin treatment. Eight patients in 476.6 person-years among atorvastatin-treated and 113 untreated patients in 4721.4 person-years had cardiovascular events (the composite end-point of fatal/non-fatal myocardial infarction, angina pectoris, coronary intervention, and fatal/non-fatal cerebrovascular disease); hazard ratio (HR) = 0.48, 95% confidence interval (CI) = 0.19-1.16, P = 0.10, and HR = 0.32, 95% CI = 0.05-1.87, P = 0.21 from IPT weighting and g-estimation method, respectively. Furthermore, seven in 475.0 person-years among atorvastatin-treated and 149 untreated patients in 4682.4 person-years had diabetes-related events (the composite end-point of sudden death, renal failure death, death as a result of hyperglycemia or hypoglycemia, diabetic gangrene and congestive heart failure in addition to cardiovascular event); HR = 0.30, 95% CI = 0.12-0.77, P = 0.01, and HR = 0.40, 95% CI = 0.09-0.89, P = 0.03 from IPT weighting and g-estimation method, respectively. When cardiovascular events were further differentiated into coronary vascular and cerebrovascular events, atorvastatin especially decreased the cerebrovascular risk.
The use of atorvastatin to lower cholesterol levels in elderly Japanese patients with type 2 diabetes mellitus appears to reduce the risk of cardiovascular and diabetes-related events.
评估阿托伐他汀对参加日本老年 2 型糖尿病干预试验（J-EDIT）的老年 2 型糖尿病患者的心血管疾病和糖尿病相关事件的预防作用。
从参加 J-EDIT 的 1173 名年龄在 65-84 岁的患者中获取数据。前瞻性随访患者 6 年，以确定阿托伐他汀对血清胆固醇水平以及心血管和糖尿病相关事件的影响。由于研究方案允许根据每位患者的临床需求开阿托伐他汀处方，因此我们将 J-EDIT 数据视为来自队列研究的数据。我们使用两种方法，即逆概率治疗（IPT）加权和 g 估计法，将研究期间的临床特征作为时间依赖性混杂因素进行调整。
总随访期为 5310.8 人年（中位随访 5.7 年），期间有 202 名患者接受了阿托伐他汀治疗。阿托伐他汀治疗可使胆固醇水平适度降低：总胆固醇降低 24.2mg/dL，低密度脂蛋白（LDL）胆固醇降低 22.9mg/dL，非高密度脂蛋白胆固醇降低 24.3mg/dL。因此，阿托伐他汀治疗后，达到 LDL 胆固醇目标水平的患者比例明显增加。在阿托伐他汀治疗的 476.6 人年中，有 8 例患者（致命/非致命性心肌梗死、心绞痛、冠状动脉介入治疗和致命/非致命性脑血管疾病的复合终点）发生心血管事件；在未接受阿托伐他汀治疗的 4721.4 人年中，有 113 例患者发生心血管事件（复合终点）（危险比（HR）=0.48，95%置信区间（CI）=0.19-1.16，P=0.10；HR=0.32，95%CI=0.05-1.87，P=0.21，分别来自 IPT 加权和 g 估计法。此外，在阿托伐他汀治疗的 475.0 人年中，有 7 例患者（复合终点为猝死、肾衰竭死亡、高血糖或低血糖导致的死亡、糖尿病坏疽和充血性心力衰竭，外加心血管事件）发生糖尿病相关事件；在未接受阿托伐他汀治疗的 4682.4 人年中，有 149 例患者发生糖尿病相关事件（HR=0.30，95%CI=0.12-0.77，P=0.01；HR=0.40，95%CI=0.09-0.89，P=0.03，分别来自 IPT 加权和 g 估计法。当将心血管事件进一步分为冠状动脉血管事件和脑血管事件时，阿托伐他汀尤其降低了脑血管风险。
在日本老年 2 型糖尿病患者中使用阿托伐他汀降低胆固醇水平似乎可降低心血管和糖尿病相关事件的风险。
