- 學位論文
台灣主動脈剝離之流行病學與手術病人使用內科藥物之效果評估
Epidemiology of aortic dissection in Taiwan and effectiveness of medical therapy on operated aortic dissection
摘要
研究背景：主動脈剝離是指主動脈壁內膜撕裂而導致管壁脆弱，容易產生破裂的情形，為一種嚴重且致死率高的疾病。目前治療指引僅建議在急性期以β- blocker 作為血壓控制的首選藥物，而手術後的藥物治療皆無明確建議。經由文獻搜尋主動脈剝離與藥品相關研究不多，對於病人之藥品處方型態亦無相關資料。在內科藥物部分，依據致病機轉statin藥品可以降低MMP分泌穩定主動脈壁的結構，需要更多臨床研究證實statin在主動脈剝離的角色，而抗血小板凝集藥品的適當性及安全性則仍有疑慮，長期使用效果仍須更多研究探討。 研究目的：本研究藉由臺灣健保資料庫全人口資料，探討主動脈剝離病人之流行病學與主動脈剝離病人手術後內科藥物使用之效果評估。 研究方法：本研究分為兩個部分，皆以臺灣健保資料庫全人口資料做為資料來源。第一部分是探討主動脈剝離之流行病學，包括發生率、盛行率、發生年齡、處方藥物形態及常見併發症，主要評估結果為全死因死亡。第二部分針對主動脈剝離手術病人術後藥品效果評估，探討手術病人基本資料與共病症、處方型態、事件發生情形及內科藥物與預後之關聯性。 研究結果與討論：流行病學研究共納入9092位主動脈剝離病人，平均年齡為64.4±15.1歲，平均追蹤時間為3.0±2.4 年，共病症以高血壓最多，其次為冠狀動脈疾病及COPD。研究期間，主動脈剝離平均年發生率為每十萬人5.6人，平均年盛行率為每十萬人19.9人，平均年死亡率為每十萬人2人。高血壓用藥中以CCB開立為最多，診斷後一年使用任一類降血壓藥物達一個月以上達92%。主動脈剝離手術病人與內科藥物效果評估研究共納入1621位主動脈剝離病人，平均年齡為58.4±13.3歲，平均追蹤時間為3.4±2.6 年，Type A AD (1142位, 70.45%)較Type B AD多(479位, 29.55%)，共病症最多仍為高血壓。長期觀察最常被處方的血壓藥品為β-blocker，手術後一年使用任一類降血壓藥品達一個月以上則高達96%。用藥組定義為用藥時間的處方持有率大於80%並將immortal time及lag time同時處理，結果顯示持續使用Aspirin顯著降低全死因死亡之風險([aHR]=0.516, 95%CI: 0.275-0.966);而持續使用statin亦有顯著降低全死因死亡的風險([aHR]=0.083, 95%CI: 0.011-0.594)。 結論：流行病學資料結果顯示台灣主動脈剝離病人之平均年發生率為每十萬人5.6人，而平均年盛行率為每十萬人19.9人。年發生率、盛行於率及死亡率都有隨時間增加的趨勢。主動脈剝離手術病人持續使用aspirin或是statin皆可顯著降低全死因死亡之風險。對於主動脈剝離病人之藥品相關研究並不多，希望其他國家在此族群領域有更多研究者及臨床試驗投入，以期歸納出對於主動脈剝離病人術後長期用藥之臨床建議。
關鍵字
主動脈剝離 ； 流行病學 ； 藥物處方評估 ； 主動脈剝離手術 ； HMG-CoA還原酶抑制劑 ； 抗血小板藥物 ； 降血壓藥物 ； 血管張力素轉換酶抑制劑 ； 乙型受體阻斷劑 ； 血管張力素受體阻斷劑 ； 鈣離子通道阻斷劑並列摘要
Background: Acute aortic dissection (AD) is a life-threatening condition associated with high rates of morbidity and mortality. Epidemiological information regarding AD remains scarce. According to current guideline, intravenous β-blocker are suggested to reduce heart rate and blood pressure in acute phase of AD. For long term control, there is no precise recommendation for operated AD patients’ long term benefit. Recent reports about matrix metalloproteinases (MMPs) may play a major role in AD. Statins can suppress MMPs production and stabilize the structure of the aortic wall. Antiplatelet therapy in patients operated for AD associate with more bleeding complications. However, more studies are needed to establish the effectiveness of these medications in AD patients. Study aim: The objective of the study was to determine current epidemiological profile of AD in Taiwanese population and evaluate the effectiveness of aspirin, statin on operated AD patients. Methods: Aortic dissection patients were collected from the Taiwan National Health Insurance Databases during 2005-2011. Incidence, prevalence, age, and prescribing pattern were investigated in epidemiological study. The effectiveness of medications focused on operated patients, using time-dependent methods to determine whether the use of medication reduced the risk of outcomes. Study endpoints included death, reoperation, and hospitalization associated with AD. Results and discussion: In epidemiological study, a total of 9,092 individuals were identified with mean age 64.4 ± 15.1 years. The most common comorbidities were known as hypertension (53.87%) followed by CAD (19.71%), COPD (13.88%). We found that the average AD incidence rates to be 5.6 per 100,000 persons per year and the average prevalence was 19.9 per 100,000 persons per year.We found that annual incidence, prevalence, and mortality showed an increasing trend in this population over time. Calcium channel blocker were the most frequently prescribed antihypertensive medication for long term observed. In operated AD patients’ cohort study, a total of 1,621 individuals (70.45% Type A AD and 29.55% Type B AD) were identified with mean age 58.4 ± 13.3 years. Multivariate models showed that the use of aspirin was associated with improved survival in overall operated AD patients ([aHR]=0.516, 95%CI: 0.275-0.966). The analysis also showed that use of statin was associated with improved survival in overall operated AD patients ([aHR]=0.083, 95%CI: 0.011-0.594). Conclusion: The rising trend of incidence, prevalence and mortality were observed during study period. The present study showed that use of aspirin and statin was associated with improved survival in overall operated AD patients. Our study provides local profile for further in-depth analyses in AD population.