分析彰化縣高齡糖尿病患者使用statin藥物是否可降低缺血性腦中風發生率

Abstract

背景：糖尿病本身就是心血管的重大風險因子之一，故根據各項研究，針對糖尿病合併高血脂的狀況，statin藥物在初級預防與次級預防均可明顯降低心血管疾病發生率與全死亡率；因應現今高齡社會，搜尋文獻後發現對於65歲以上的高齡糖尿病患者使用statin作為初級預防的實證證據相對不足。合併三個包含高齡糖尿病族群使用statin的隨機分派研究做統合分析，結果發現使用statin做初級預防的效益並未達到統計顯著水準；在10個觀察性研究的統合分析則發現高齡糖尿病族群使用statin有初級預防的效益，並達到統計顯著水準；觀察性研究與隨機分派研究似乎結論不一。 研究目的：腦血管疾病是我國人死亡與失能的主要原因之一，其中缺血性腦中風佔大約7成，而糖尿病是缺血性腦中風的重大風險因子之一，高齡糖尿病患者尤其是缺血性腦中風的高風險族群。故本研究針對彰化縣的高齡(65歲以上)糖尿病患者未併發缺血性腦中風使用statin藥物是否可降低缺血性腦血管疾病發生率作分析，探討65歲以上的高齡糖尿病患者使用statin藥物做為初級預防的效益。 研究方法：本研究使用回溯性世代研究，利用彰化縣「糖尿病共同照護資訊系統」資料庫收集研究族群，以2013年08月01日至2017年12月31日中，至少連續追蹤兩年以上且無腦中風病史的高齡(滿65歲)糖尿病個案共3097人；其中至少使用一年以上statin個案為實驗組，共有1341人；完全未曾使用statin的個案為對照組，共有987人，排除用藥未滿一年個案；並利用腦中風出院準備服務計畫資料追蹤以上個案其2018年至2020年是否有發生缺血性腦中風事件與入院時間，估計其發生率，並使用存活分析法，分析有無使用statin藥物、糖尿病罹病年數、實驗室檢查資料、吸菸等因子對缺血性腦中風發生率之影響。 結果: 使用藥物組共1341人，其中有37人入院，估計缺血性腦中風發生率為9.2/1000人年；無使用藥物組中共987人，其中有36人入院，估計缺血性腦中風發生率為12.1/1000人年。 存活分析最適模式顯示，有使用statin藥物的風險對比值為0.762，95%Cl為0.478~1.215，未達統計上顯著差異；低密度指蛋白膽固醇小於100mg/dl的風險對比值為0.556，95%Cl為0.348~0.887，有統計上顯著差異；糖尿病罹病年的風險對比值為1.036，95%Cl為1.002~1.071，有統計上顯著差異；有使用降血壓藥物的風險對比值為1.444，95%Cl為0.785~2.656，未達統計上顯著差異；實驗室檢查三酸甘油脂的風險對比值為1.000，95%Cl為0.997~1.004，未達統計上顯著差異；低密度膽固醇數值的風險對比值為1.012，95%Cl為1.003~1.022，有統計上顯著差異。 結論:本回溯性研究納入的糖尿病收案對象來自全縣各社區民眾，由各地衛生所收案，可代表本縣各地區基層醫療的主要照顧族群；研究發現低密度脂蛋白膽固醇控制在100mg/dl以下可降低0.556倍的缺血性腦中風發生率；在低密度脂蛋白膽固醇控制在100mg/dl以下的狀況，使用statin藥物可能有額外的好處；低密度脂蛋白膽固醇每上升1mg/dl會增加1.2%的缺血性腦中風發生率；糖尿病罹病年每多一年，缺血性腦中風的發生率增加1.036倍。臨床上，應積極降低高齡糖尿病患者的低密度脂蛋白膽固醇，較低的低密度脂蛋白膽固醇有較好的預後；政策上，應針對高風險個案提供篩檢，及早發現糖尿病個案，並早期積極介入以降低個案將來缺血性腦中風的發生率。

Background Diabetes is one of the major cardiovascular risk factors. According to past studies, for the condition of diabetes combined with hyperlipidemia, statin drugs can significantly reduce the incidence of cardiovascular diseases and overall mortality in primary prevention and secondary prevention. In response to today's aging society, little evidence show the use of statin as primary prevention in elderly patients with diabetes over the age of 65. Aims This study aims to analyze whether the use of statin drugs can reduce the incidence of ischemic stroke in elderly (over 65 years old) diabetic patients in Changhua County Materials and methods This study is a retrospective cohort study. The subjects aged over 65 years old who received care from 27 local health centers in Changhua County from August 1, 2013 to December 31, 2017, for at least two consecutive years were enrolled. A total of 3097 patients with diabetes were enrolled; 1341 subjects in the intervention group were those who had used statin for at least one year; 987 subjects were in the control group who had not used statin at all, and those who had used statin for less than one year were excluded. We also use the data of Discharge Planning intervention on stroke patient in Changhua County to track whether the above cases were hospitalized for ischemic stroke and the admission date from 2018 to 2020 to estimate the incidence. The Cox proportional harzard model was used to assess the effects of statin use, low-density lipoprotein-Cholestrol(LDL-C)<100mg/dl or LDL-C value, diabetes duration, other laboratory data and other risk factors on the incidence of ischemic stroke. Results The incidences of ischemic stroke were 9.2/1000 person-years and 12.1/1000 person-years in the intervention group and the control group, respectively. By using the multivariate regression analysis, the hazard ratio of statin use was 0.762 (95%Cl, 0.478-1.215, P=0.25). The hazard ratio for LDL-C<100mg/dl was 0.556 (95% Cl, 0.348-0.887, P=0.0139). The hazard ratio for LDL-C value(mg/dl) was 1.012 (95% Cl, 1.003-1.022), P=0.0095). The hazard ratio for diabetes duration was 1.036 (95% Cl, 1.002-1.071, P=0.035). The hazard ratio of using antihypertensive drugs was 1.444(95% Cl, 0.745-2.656, P=0.23). The hazard ratio for blood triglycerides was 1.000(95% Cl, 0.997-1.004, P=0.75). For a meta-analysis in combination of three randomized control trials, benefit of using statin for primary prevention did not reach a statistically significance. Conclusions The subjects included in this retrospective study come from various communities in Changhua county, and the cases are received by the local health centers, which can represent the main target groups of primary medical care in Changhua county. LDL-C control below 100mg/dl has a lower incidence of ischemic stroke(HR= 0.556, 95% Cl, 0.348-0.887). In the condition that the low-density lipoprotein cholesterol is controlled below 100mg/dl, the use of statin may have additional benefits. Every 1 mg/dl increase in LDL cholesterol value increases the incidence of ischemic stroke by 1.2%. Lower LDL-C has a better prognosis. The incidence of ischemic stroke increased by 1.037 times for each additional year of diabetes duration. Health policies should provide screening for high-risk cases, early detection of diabetes cases, and early intervention can reduce the incidence of ischemic stroke in the future.