評估長期使用雙重抗血小板凝集藥物在低危險性急性冠心症的療效與此疾病的相關危險因子探討- 以高屏地區為例

The Evaluation of Effectiveness in Long-term Dual-Antiplatelet Agents (Clopidogrel, Aspirin) Use for Low Risk Acute Coronary Syndrome and Other Risk Factors of This Disease - Example of Kao-Ping Area

林嘉慶(Chia-Ching Lin)

指導教授 ： 蔡東榮

高雄醫學大學/藥學院/臨床藥學研究所/碩士(2008年)

摘要

研究目的：非ST波上升的急性冠心症 (ACS) 是屬於危險性較低的急性冠心症，目前在長期治療上主要是以抗血小板凝集藥物為主。抗血小板凝集藥物又以clopidogrel和aspirin為主。現行療法有文獻指出可以合併二者來達到更好的療效，但亦有文獻不贊同此說法。因此，本研究希望利用台灣的資料，來得到何種療法及危險因子可以降低疾病的再發。
研究方法：本研究為一個觀察性、回溯性的世代研究。主要資料來源為台灣健康保險局。由高高屏地區健保局得到低危險性急性冠心症病患的追蹤資料，主要追蹤期為2004年四月至2007年三月。納入病患的條件為：有使用clopidogrel, aspirin或二者合併使用且住院的診斷碼為：ICD: 410~414。排除條件為：住院期間有做過心臟手術、不可控制的高血壓、住院前有規律服用抗凝血藥物。之後使用Kaplan-Meier estimate來評估combine與antiplatelet agent單獨使用的存活率、Cox regression和Multiple logistic regression來評估影響病患存活的其他變因。
研究結果：一共473位病人，被分為三組：clopidogrel組228人、aspirin組195人、combine組50人。在存活分析方面，combine組並不會比任一個抗血小板凝集藥物單用的效果好(P=0.2091 for clopidogrel, P=0.8336 for aspirin)。在其他疾病相關分析，有心衰竭或糖尿病的病患相對於沒有心衰竭或糖尿病的病患有較高的risk ratio (分別為RR=1.52, P=0.0031; RR=1.41, P=0.0345)。
研究結論：在本研究期間，針對疾病再發方面：合併兩種抗血小板凝集藥物並不會比單獨使用效果來的好。而與疾病再發相關的危險因子有：心衰竭、糖尿病。對於疾病再發的有益因子有：合併使用鈣離子通道阻斷劑、執行心臟手術、延長抗血小板凝集藥物的使用天數。

關鍵字

clopidogrel ； aspirin ； 急性冠心症

並列摘要

Objectives: Non-ST elevation acute coronary syndrome (ACS) is considered as low risk ACS. The long-term therapy focuses on antiplatelet agents, such as clopidogrel, aspirin, or combination. Some studies have proved the combination therapy was better than mono-therapy, but some have showed the opposite evidence. This study aims to analyze what factors can reduce the recurrence of disease with the local data.
Methods: This study was an observational and retrospective cohort study using the healthcare claims data in Taiwan, which includes 473 patients with low risk of acute coronary syndrome enrolled from National Health Insurance data of Kao-ping area from April, 2004 to March, 2007. Inclusion criteria: use of clopidogrel, aspirin or both, and intersect with the primary outcomes which were defined by ICD-9 code (ICD: 410~414). Exclusion criteria: with cardiac surgery during hospitalization, uncontrolled hypertension and routine use of anticoagulants before included. Then the Kaplan-Meier estimate was used to evaluate the difference of survival rate in three groups (clopidogrel, aspirin, and combine). Cox regression and Multiple logistic regression were also used to detect the real variables that influenced the survival rate.
Results: All patients were divided into three groups: clopidogrel alone (N=228), aspirin alone (N=195) and clopidogrel plus aspirin (combined therapy, N=50). In survival analysis, the combination therapy was not better than clopidogrel or aspirin alone (P=0.2091 for clopidogrel, P=0.8336 for aspirin). In other analysis about the risk factors of the disease, patients with heart failure (HF) and Diabetes Mellitus (DM) had higher risk ratio (RR=1.52, P=0.0031; RR=1.41, P=0.0345 respectively) than those without comorbidity.
Conclusion: Combine therapy (dual-antiplatelets) was not better than clopidogrel alone or aspirin alone in the study period. Other risk factors about disease recurrence were HF and DM. Other beneficial factors about disease recurrence were concurrent use of calcium channel blocker (CCB), revascularization and prolong use of antiplatelet agents.

並列關鍵字

clopidogrel ； aspirin ； acute coronary syndrome.

參考文獻

2007 UpToDate® • www.uptodate.com , Overview of the management of unstable angina and acute non-ST elevation (non-Q wave) myocardial infarction.

2008 UpToDate® • www.uptodate.com, Pathogenesis of plaque rupture in acute coronary syndrome.

ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction

http://www.phri.ca/cure/index.html

Almsherqi, Z. A., McLachlan, C. S. & Sharef, S. M. 2007. Non-bleeding side effects of clopidogrel: Have large multi-center clinical trials underestimated their incidence? International Journal of Cardiology, 117: 415-417.