- 學位論文
評估心房顫動患者缺血性中風後使用抗血栓劑之持續比例、療效及安全性
Evaluation of the Persistence Rate, Efficacy and Safety of Antithrombotic Agents in Patients with Atrial Fibrillation Following Ischemic Stroke
摘要
研究背景 心房顫動會使病患缺血性中風風險增加五倍以上，因此在此類病患中依據不同的中風危險分級給與不同的抗血栓劑以預防中風是很重要的。 美國心臟病學院 / 美國心臟協會/ 歐洲心臟病學會所提出之臨床指引（2006）指出，在患有心房顫動且曾發生過缺血性中風的病患中，抗凝血劑warfarin的中風預防效果是抗血栓劑中最好的。 在台灣，心房顫動病患在缺血性中風或暫時性腦出血出院後開立warfarin的比例只有28％，此比例遠低於美國約95%的開立比例，顯見台灣之抗凝血劑處方率仍有待改善。 目的 本研究目的為瞭解署立雙和醫院、臺北醫學大學附設醫院及萬芳醫學中心中心房顫動患者在發生缺血性中風後，出院時使用抗血栓劑的處方開立情形、開立後持續使用者的比例，並對持續用藥的病患做藥物療效及安全性之存活分析，及探討抗凝血劑之使用是否恰當。 方法 本研究為一回溯性研究，收錄在臺北醫學大學附屬三間醫院於2006年5月1日至2010年8月31日間因缺血性中風入院之心房顫動患者。藉由各醫院之中風資料庫及病歷回溯方式做資料蒐集，再對病患於中風出院後抗凝血劑warfarin及抗血小板劑(aspirin, dipyridamole, clopidogrel) 之持續使用比例做分析。 研究中主要結果定義為栓塞事件、重大出血事件或死亡三種事件；次要結果則針對warfarin使用者國際標準化凝血酶原時間比值（INR）分佈在治療範圍內與否做探討。以Kaplan-Meier estimate分析在抗血栓劑使用者日後發生各種研究相關結果情形，並以Cox proportional-hazards regression model 來校正危險因子並檢視用藥與結果之相關性。 結果 本研究共收錄291位因缺血性中風入院之心房顫動病患，病患於中風出院時之warfarin處方率為55.3%，有6.9% 病患在出院時或出院後一個月內未開立抗血栓劑。 在出院後24個月內，各藥物持續使用者佔其出院開方者之比例於抗凝血劑warfarin為 53.8%，抗血小板劑為51.5%，而在併用warfarin及抗血小板劑之病患中為22.5%。 在各組藥物使用者中，以warfarin為參考的情形下，抗血小板劑的栓塞事件校正後危險比為3.36 (95% CI, 1.05-10.73, p <0.05)，重大出血事件及死亡校正後危險比未達統計學上顯著差異。在warfarin的使用者在研究期間中，大約有65%的病人月分佈在INR 小於2.0的範圍中，且只有25.3%的病人月分佈在理想治療範圍（INR 2.0-3.0）。 結論 由本研究結果可得知在心房顫動患者發生缺血性中風後開立warfarin之處方率處於偏低情形，即使病患有開立抗血栓劑處方，在發生缺血性中風後一年持續使用者的比例有大幅度的降低趨勢。將warfarin和抗血小板劑做比較發現，持續使用warfarin之患者有較低的栓塞事件風險，但在重大出血、死亡事件方面兩組並無顯著差異。 另外，顯示抗凝血治療之品質仍亟需改善，此結果也強調了未來在台灣建立抗凝血劑藥師門診的重要性。
並列摘要
Background Atrial fibrillation (AF) is associated with a five-fold increase in the risk of stroke. According to the 2006 practice guideline for the management of patients with AF proposed by American College of Cardiology (ACC), American Heart Association (AHA) Task Force, and the European Society of Cardiology (ESC), warfarin is the most effective drug to prevent recurrent stroke in AF patients. In Taiwan, the prescribing rate of warfarin at stroke discharge in AF patients is about 28%, which is lower than the US prescribing rate of 95%. The prescribing rate of warfarin in AF patients with higher risk of thromboembolism needs to be improved in Taiwan. Purpose The study was designed to determine the prescribing pattern of antithrombotic therapy at discharge, percentage of persistent users, and efficacy and safety of antithrombotic agents for secondary prevention of stroke in AF patients in three Taipei Medical University (TMU)-affiliated teaching hospitals. This study was aimed to investigate the prescribing rate and quality of anticoagulant treatment in AF patients with prior ischemic stroke in three hospitals in Taiwan. Methods This was a retrospective study of AF patients (n = 291) following ischemic stroke during May 1, 2006 through August 31, 2010 in TMU-affiliated teaching hospitals. Data were obtained from stroke databank and medical records in each hospital. The percentage of persistent users of warfarin, antiplatelet drugs (APD: aspirin, dipyridamole and clopidogrel) or combined use of warfarin and APD was examined. Primary outcomes were thromboembolic events, major bleeding events, or death and the secondary outcome was the quality of anticoagulation control with warfarin therapy. These outcomes of each antithrombotic therapy were analyzed by Kaplan-Meier estimates and adjusted with the Cox proportional-hazards regression model. Results The prescribing rate of warfarin was 55.3% in the study population. Over the first 24 months after discharge, among the drug users, the proportion of persistent users of antithrombotic agents dropped to 53.8% in warfarin group, 51.5% in APD group, and 22.5% in warfarin plus APD group. The adjusted hazard ratio for APD compared with warfarin was 3.36 (95% CI, 1.05-10.73, p <0.05) for thromboembolic event such as ischemic stroke and transient ischemic attack; no difference was found in major bleeding events and death. Among warfarin users, about 65% of patient-time was in the INR level of less than 2.0 and only 25.3% of time reached the therapeutic range of INR 2.0-3.0 during the study period. Conclusion The present results suggest that the prescribing rate of warfarin in AF patients with previous ischemic stroke was low, and the rate of persistent antithrombotic agent users declined progressively in the first 24 months after discharge. Compared with APD, warfarin users were associated with a lower risk of thromboembolism included recurrent stroke and/or transient ischemic attack. These data also revealed that the quality of anticoagulation control with warfarin therapy needs to be improved immediately. Finally, these findings suggest the pharmacist-provided anticoagulation management service should be promoted in Taiwan.