台灣地區長期透析病患使用腎素- 血管張力素阻斷劑與心血管疾病風險之相關研究

The association between renin-angiotensin system blockade and cardiovascular risk in long-term haemodialysis patients in Taiwan

李佾璇(Yi-Hsuan Lee)

指導教授 ： 蔡東榮

高雄醫學大學/藥學院/藥學研究所碩士在職專班/碩士(2014年)

摘要

研究背景:
全球血液透析的盛行率逐年增加。在台灣，政府於1995年推出全民健康保險政策後，台灣血液透析人口迅速增加。相較於腎功能正常的病患，血液透析患者對於心血管事件發生率有較高的風險，包括病發率和死亡率。心血管疾病是長期血液透析患者最常發生的併發症。腎素-血管張力素阻斷劑雖有降壓及延緩腎臟功能惡化作用，但對於須長期洗腎病患的預後是否有益處，仍有待研究其相關連性。
研究方法：
本研究以回溯性世代研究做為研究設計，藉由1997~2009年全民健康保險研究資料庫百萬抽樣歸人檔進行分析。研究對象為台灣地區須長期血液透析病患，依研究定義，病患納入1999~2006年間，連續洗腎三個月以上，且申請重大傷病檔的病患。我們分析長期血液透析病患藥物使用情形及其相關預後，並將研究對象區分為暴露組(有使用RASB)和非暴露組(沒有使用RASB)。分析兩組病人死亡和心血管疾病風險。
研究中以描述性統計敘述病患基本資料，包括年齡、地區、社經地位、共病症以及使用藥物。存活分析皆使用Kaplan-Meier method進行分析，並以Log-rank test分析暴露組與非暴露組間是否具有統計學上顯著差異，以Cox proportional hazards regression校正干擾因子。
研究結果:
研究期間共納入15434位觀察對象，其中，7820人有使用腎素-血管張力素阻斷劑治療；7612人從未使用。在暴露組中，2535例患者單獨使用ACEI，1324人單獨使用ARB，其餘3961患者為轉換使用藥物（ACEI轉換成ARB）。病患基本狀態分析中，有使用RASB的病患年齡較輕（66.3歲vs 68.7歲，P <0.001），其中有較高比例罹患高血壓（22.59%比15.75%，P <0.001）和糖尿病（33.55 %比21.91%，P <0.001）。藥物使用狀況分析中，暴露組病人較常使用β受體阻斷劑，鈣離子通道阻斷劑，α-受體阻斷劑，利尿劑，statin，抗血小板藥物，和糖尿病藥物。病患平均觀察時間，暴露組和非暴露組分別為1759.78天和1590.63天（P <0.001）。研究主要觀察結果為死亡，觀察期間，使用RASB的病患，有2829人死亡；無使用RASB的病患，有2637人死亡。死亡率分別為33.8 %和37.1%。使用RASB的病患，有較低死亡風險(aHR=0.79；95% CI=0.69-0.91)。研究的次要觀察結果為心血管疾病發生率，觀察期間，使用RASB的病患，有4166人發生心血管疾病；無使用RASB的病患，1100人發生心血管疾病，心血管疾病的發生包括中風、心衰竭和心肌梗塞。暴露組和非暴露組兩組病人心血管事件發生率分別為52.16%和14.40%。
結論:
腎素-血管張力素阻斷劑類藥物的使用，能夠增加病人存活機率，有效降低長期血液透析病患的總體死亡率；但此類藥物的使用，對於長期血液透析病患心血管事件發生率，並沒有顯著降低風險的效果。

關鍵字

血液透析 ； 腎素-血管張力素阻斷劑 ； 死亡率

並列摘要

Background:
The worldwide incidence and prevalence of End-Stage Renal Disease (ESRD) requiring dialysis is increasing. The incidence and prevalence of patients on dialysis in Taiwan increased rapidly after 1995, the launch year of National Health Insurance (NHI). Compared with patients with normal renal function, patients on long-term dialysis are at increased risk of cardiovascular events, which comprise a major cause of morbidity and mortality
Cardiovascular events is among the most frequent complications of patients on long-term haemodialysis. The benefits of renin–angiotensin system (RAS) blocker on the outcomes of these patients have yet to be determined.
Methods:
The current study conducted a nationwide observational study using data from the Taiwan National Health Insurance Research Database(NHIRD) , between 1997 and 2009. We used the International Classification of Diseases, 9th revision, clinical modification (ICD-9-CM) codes to define the diseases.
Our study subjects were patients on long-term HD receiving regular HD more than 3 months during 1999–2006, and the patients were identified through the catastrophic illness registry in the NHIRD. This study was approved by the National Health Research Institute, and all the data are delinked information. Confidentiality was ensured by abiding by the NHI Bureau data regulations. We used the NHIRD between 1997 and 2009 for co-morbidity and follow-up analysis purposes .This study enrolled patients with long term haemodialysis under treatment with medications. We further classified the study sample into two groups. New users of a RAS blocker (RASB; i.e. an ACEi or an ARB ) were selected to compare with non-RASB users.
We used Cox proportional hazards regression to compare the risk of all-cause mortality and the incidences of cardiovascular events. Stratified analyses and RASB therapy duration as a time-dependent covariate were also performed.We also considered other covariates in this study, including cumulative days taking an RASB, age, gender, urbanization level, medications, and co-morbidities, within the 2 years before the first time received haemodialysis
Results:
In all, 15434 patients were enrolled in the study. Of these, 7820 patients took an RASB and 7612 patients did not take any RASB. In the treatment group, 2535 patients use ACEI only,1324 patients use ARB only, and 3961 patients replaced the drug use (ACEI to ARB). Those treated with an RASB were younger (66.3 years vs. 68.7 years, P < 0.001), which had a higher prevalence of hypertension (22.59% vs. 15.75%, P < 0.001) and diabetes (33.55% vs. 21.91%, P < 0.001).At the time of enrolment, compared with the patients in the control group, patients in the treatment group more commonly used beta-blockers, calcium channel blockers, alpha-blockers ,diuretics, statins, antiplatelet drugs ,and diabetes drugs. The mean follow-up periods were 1759.78 and 1590.63 days in the treatment and control groups, respectively (P < 0.001) . The primary outcome was all-cause mortality during a follow-up periods. Among RASB users, 2637 deaths compared with 2829 deaths among non-RASB users. mortality rates were 33.8% and 37.1% for patients receiving and those not receiving an RASB. Log-rank tests of unadjusted survival showed a significantly lower mortality rate in the treatment group than in the control group (P <0.001).
Conclusion:
RASB therapy reduced all-cause mortality in patients on long-term haemodialysis.But this study did not provide a beneficial effect of RASB for the cardiovascular events in long-term HD patients .

並列關鍵字

Haemodialysis ； Renin–angiotensin system ； ACEI ； ARB ； Mortality

參考文獻

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