心血管用藥在透析病人之預防效果

The effect of cardiovascular prevention drugs in dialysis patients

吳秉勳(Ping-Hsun Wu)

指導教授 ： 陳鴻鈞

高雄醫學大學/醫學院/醫學研究所碩士班/碩士(2015年)

https://doi.org/10.6832/KMU.2015.00115

摘要

背景:末期腎臟疾病與心血管疾病的風險增加有關，而心血管疾病則會增加末期腎臟疾病的死亡率與併發症。然而，截至目前，仍沒有隨機對照研究比較aspirin與thienopyridines兩種藥物對於透析病人急性冠心症的次及預防效果。此外，大部分statin治療的隨機對照研究主要是針對血液透析或慢性腎臟衰竭的病患，statin藥物針對腹膜透析病患心血管疾病預防的研究仍然缺乏，因而需要更進一步的研究。我們利用台灣健保資料庫設計了全國性的追蹤研究，去評估兩個心血管預防用藥在透析病人運用的重要問題。第一個研究比較aspirin與thienopyridines兩種藥物在台灣透析病人有發生急性冠心症者，對於減少急性冠心症復發與死亡率的效用，第二個研究探討statin藥物在血液透析或腹膜透析病人是否可以減少心血管事件的發生機會。
方法:在第一個研究中，時間從1998到2006年，我們篩選出56,866位新進入長期透析(包含血液透析與腹膜透析)的病人。在這群透析的病人中，有發生急性冠心症住院者納入研究分析，共有1,350位病人接受aspirin做為急性冠心症的次及預防，有946位病人接受thienopyridines做為急性冠心症的次及預防。每位病人從第一次發生急性冠心症住院開始追蹤兩年的時間，主要研究結果包含急性冠心症的復發與總死亡率。在第二個研究中，時間從1998到2006年，我們篩選出新進入長期血液透析與腹膜透析的病人，其中接受statin的治療第一年內的藥品持有率(Medication possession ratio)大於80%以上者有725位病人，小於80%以下者有2,114人，在三年的追蹤期間，主要研究結果為主要心血管事件，其中包含缺血性腦中風或急性冠心症住院者。
結果:在第一個研究中， thienopyridines使用者相較於aspirin使用者有較高的急性冠心症復發率(26.64% vs. 17.48%, P < 0.001)。急性冠心症復發的校正風險比值為1.56 (95%信賴區間是1.30到1.88)，而總死亡率的校正風險比值為1.15 (95%信賴區間是0.99到1.34)。在第二個研究中，statin使用第一年內藥品持有率(Medication possession ratio)大於80%以上者相較於藥品持有率小於80%以下者，在血液透析病人並沒有達統計學上差異，有較低的主要心血管事件住院率(29.35% vs. 25.82%)，其校正風險比值為1.06 (95%信賴區間是0.98到1.13)。其中因急性冠心症與缺血性腦中風住院的校正風險比值分別為1.14 (95%信賴區間是1.05到1.23)與0.85 (95%信賴區間是0.75到0.96)。而在腹膜透析病人同樣也沒有達統計學上差異，有較低的主要心血管事件住院率(6.34% vs. 7.05%)，其校正風險比值為0.91 (95%信賴區間是0.65到1.27)。其中因急性冠心症與缺血性腦中風住院的校正風險比值分別為0.9 (95%信賴區間是0.61到1.32)與0.98 (95%信賴區間是0.5到1.89)。
結論:從透析病人的全國回溯世代研究分析可以發現，aspirin治療相較於thienopyridines較能有效預防急性冠心症的再次發生，但是無法下降總死亡率。而statin藥物在血液透析與腹膜透析病人心血管事件的預防，第一年內藥品持有率大於80%以上者相較於小於80%以下者，無法減少主要心血管事件的住院率。

關鍵字

血液透析 ； 腹膜透析 ； 急性冠心症 ； 心臟血管事件 ； 腦中風 ； 心血管預防藥物 ； 阿斯匹林 ； 噻吩吡啶類藥物 ； 史他汀類藥物 ； 世代研究 ； 族群基礎研究 ； 台灣健保資料庫

並列摘要

Background:End-stage renal disease is associated with an increased risk of cardiovascular risk, which is an important cause of morbidity and mortality in dialysis patients. However, there is so far no randomized study comparing the efficacy of aspirin versus thienopyridines for secondary prevention of acute coronary syndrome in dialysis patients. Besides, most of the statin treatment randomized studies focus on hemodialysis or chronic kidney disease. The study of statin use for cardiovascular prevention in peritoneal dialysis patients is still sparse and need further investigate. Therefore, we conduct a nationwide follow-up study, based on the Taiwan National Health Insurance Research Database, to evaluate two issue of cardiovascular prevention drugs used in dialysis. First study aimed to compare the efficacy of aspirin versus thienopyridines in reducing the risk of recurrent acute coronary syndrome and mortality in Taiwanese dialysis patients who were hospitalized with acute coronary syndrome. Second study aimed to evaluate the efficacy of statin in reducing the subsequent risk of cardiovascular event in hemodialysis and peritoneal dialysis patients.
Methods:In the first study, we identified 56,866 incident dialysis patients who initiated long-term dialysis therapy, either hemodialysis or peritoneal dialysis between 1998 and 2006 and were hospitalized with an episode of acute coronary syndrome. Of the dialysis patients who were hospitalized with acute coronary syndrome, 1,350 received aspirin and 946 received thienopyridines for secondary prevention of acute coronary syndrome. Patients’ outcomes were reviewed for 2 years from the first day of hospitalization for acute coronary syndrome. Primary outcomes included recurrent acute coronary syndrome and all-cause mortality. In the second study, we identified incident hemodialysis and peritoneal dialysis patients between during 1998 and 2006. Of the peritoneal dialysis patients, 725 received statin with medication possession ratio (MPR) more than 80% in the first year and 2,114 received statin with MPR less than 80% for hyperlipidemia control. During the 3 years follow up, the primary outcomes of the study was major cardiovascular event, which include hospitalization for acute coronary syndrome and ischemic stroke.
Results:In the first study, thienopyridines users experienced significantly more recurrent acute coronary syndrome than aspirin users (26.64% vs. 17.48%, P < 0.001). The adjusted hazard ratio [HR] in relation to recurrence of acute coronary syndrome was 1.56 (95% confidence interval [CI]: 1.30 to 1.88) and to all-cause mortality was 1.15 (95% CI: 0.99 to 1.34). In the second study, statin with MPR more than 80% users were not significantly lower hospitalization for major cardiovascular event than statin with MPR less than 80% users (29.35% vs. 25.82%), whereas adjusted HR was 1.06 (95% CI: 0.98 to 1.13) in hemodialysis patients. The adjusted HRs of hospitalization for acute coronary syndrome and ischemic stroke were 1.14 (95% CI: 1.05 to 1.23) and 0.85 (95% CI: 0.75 to 0.96). As for peritoneal dialysis patients, statin with MPR more than 80% users were not significantly lower hospitalization for major cardiovascular event than statin with MPR less than 80% users (6.34% vs. 7.05%), whereas adjusted HR was 0.91 (95% CI: 0.65 to 1.27). The adjusted HRs of hospitalization for acute coronary syndrome and ischemic stroke were 0.9 (95% CI: 0.61 to 1.32) and 0.98 (95% CI: 0.5 to 1.89).
Conclusions:In this retrospective analysis in a national representative cohort of dialysis patients, aspirin treatment appeared more effective than thienopyridines for secondary prevention of acute coronary syndrome and showed a non-significant trend towards lower risk of all-cause mortality. As for statin prevention for cardiovascular events in hemodialysis and peritoneal dialysis patients, statin use with MPR more than 80% had no statistically significant effect on the composite end point of hospitalization for acute coronary syndrome and ischemic stroke than statin use with MPR less than 80%.

並列關鍵字

hemodialysis ； peritoneal dialysis ； acute coronary syndrome ； cardiovascular events ； ischemic stroke ； cardiovascular prevention drugs ； aspirin ； thienopyridines ； statin ； cohort study ； population-based study ； Taiwan National Health Insurance Research Database

參考文獻

1.Kontodimopoulos N, Niakas D. An estimate of lifelong costs and QALYs in renal replacement therapy based on patients' life expectancy. Health Policy. Apr 2008;86(1):85-96.

2.Ranasinghe P, Perera YS, Makarim MF, Wijesinghe A, Wanigasuriya K. The costs in provision of haemodialysis in a developing country: a multi-centered study. BMC Nephrol. 2011;12:42.

3.Yang WC, Hwang SJ. Incidence, prevalence and mortality trends of dialysis end-stage renal disease in Taiwan from 1990 to 2001: the impact of national health insurance. Nephrol Dial Transplant. Dec 2008;23(12):3977-3982.

4.Mai-Szu Wu, I-Wen Wu, Chia-Pang Shih, and Kuang-Hung Hsu. Establishing a Platform for Battling End-stage Renal Disease and Continuing Quality Improvement in Dialysis Therapy in Taiwan. Acta Nephrologica 2011;25(3):148-153.

5.Tsai SY, Tseng HF, Tan HF, Chien YS, Chang CC. End-stage renal disease in Taiwan: a case-control study. J Epidemiol. 2009;19(4):169-176.