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研究生:王敏如
研究生(外文):Min-Ju Wang
論文名稱:心房顫動病患使用抗血栓劑符合準則與否和心血管事件發生關聯性之探討
論文名稱(外文):Relationship between Guideline-adherent Anti-thrombotic Treatment and Cardiovascular Events in Patients with Atrial Fibrillation
指導教授:林立人林立人引用關係戴淑華戴淑華引用關係高雅慧高雅慧引用關係
指導教授(外文):Li-Jen LinShu-Hua TaiYea-Huei Kao Yang
學位類別:碩士
校院名稱:國立成功大學
系所名稱:臨床藥學研究所
學門:醫藥衛生學門
學類:藥學學類
論文種類:學術論文
論文出版年:2008
畢業學年度:96
語文別:中文
論文頁數:140
中文關鍵詞:warfarin心房顫動抗血栓劑中風準則心血管事件
外文關鍵詞:strokewarfarinantithrombotic therapyatrial fibrillationcardiovascular eventsguideline
相關次數:
  • 被引用被引用:1
  • 點閱點閱:516
  • 評分評分:
  • 下載下載:74
  • 收藏至我的研究室書目清單書目收藏:1
研究背景
心房顫動病患每年約有5%的風險會發生缺血性中風,是正常人風險的2-7倍,此種心因性中風,往往造成病人死亡或失能。臨床試驗已證實warfarin可下降整體中風的相對風險64%,而抗血小板製劑僅可下降22%,但是warfarin會增加嚴重出血的機會,因此心房顫動準則建議應依據病患的中風危險性來選擇最恰當的抗血栓劑。然而國內外研究結果顯示,符合準則使用抗血栓劑的比例皆偏低。本研究目的為評估心房顫動病患符合準則用藥與否和心血管事件發生的關聯性。

研究方法
利用2000-2004年全民健康保險資料庫,對象為2002年7月1日至2003年6月30日期間,門診出現兩次以上「427.31」診斷碼且大於18歲的心房顫動病患。以ACC/AHA/ESC (2001)心房顫動準則為基準,評估栓塞危險因子、warfarin禁忌症後,進一步將病患使用抗血栓劑情形區分成高於準則、符合準則、低於準則,最後利用多變項逐步迴歸法校正後,找出心血管事件的預測因子。

結果
最終收錄29,090人為研究族群,栓塞危險因子以高血壓(66.07%)、心衰竭(41.18%)為最多;warfarin禁忌症以肝炎或肝硬化(13.07%)比例最高;抗血小板製劑使用組佔了一半以上(54.30%);整體符合準則的比例為27.89%,而大部分是低於準則(68.19%)。至於對心血管事件發生的影響,「低於準則」顯著增加死亡機會(OR=1.43, 95%CI:1.23-1.67, p<0.0001),但沒有增加腦部缺血(OR=0.98, 95%CI:0.86-1.10, p=0.6871)及其他栓塞事件(OR=0.98, 95%CI:0.77-1.24, p=0.8644),而「高於準則」也不影響顱內出血(OR=1.53, 95%CI:0.71-3.29, p=0.2765)及腸胃道出血(OR=1.35, 95%CI:0.91-1.99, p=0.1331)的發生。

結論
臺灣的心房顫動病患符合準則使用抗血栓劑的比例很低,在低於準則情形下,會增加死亡的風險,但對栓塞性事件並沒有影響,然而,準則建議在臨床上的適用性仍值得探討。
Background
For patients with atrial fibrillation (AF), the annual risk of stroke is approximately 5%, 2- to 7- fold higher compared to those with sinus rhythm. Such cardioembolic strokes are often fatal or severely disabling. Randomized trials have shown that warfarin reduces the relative risk of stroke by 64% while anti-platelet agents only reduces by 22%. However, warfarin is also associated with an increased risk of major bleeding. Therefore, guideline on AF management suggests that the anti-thrombotic agents should be selected according to patient’s stroke risk. Nevertheless, many studies have shown that the proportion of guideline adherence of anti-thrombotic agents is still low. The aim of this study is to evaluate the association between cardiovascular events and guideline adherence.

Method
We included AF patients who were documented twice with ICD9-CM coded of ‘427.31’ in ambulatory department and older than 18 years in non-sampled National Health Insurance claims database from 1 Jul 2002 through 30 June 2003. We estimated the embolic risks and contraindications of warfarin based on ACC/AHA/ESC (2001) AF guideline. After evaluating anti-thrombotic agents, we defined three treatment condition, which are overtreatment, adherence and undertreatment. Moreover, stepwise multivariate logistic regression analysis was performed to figure out the predictors of cardiovascular events.

Results
29,090 patients with AF were included in the study, and among them, the common embolic risk factors were hypertension (66.07%) and heart failure (41.18%). Most people with contraindications of warfarin had a history of hepatitis or liver cirrhosis (13.07%). Anti-platelet agents for thrombotic prophylaxis were taken by half of patients (54.30%). The overall adherence rate was 27.89% indicating undertreatment in most of the patients (68.19%). As cardiovascular events, undertratment was associated with significantly increased overall mortality (OR=1.43, 95%CI:1.23-1.67, p<0.0001) but didn’t increase ischemic stroke (OR=0.98, 95%CI:0.86-1.10, p=0.6871) and other embolic events (OR=0.98, 95%CI:0.77-1.24, p=0.8644). Overtreatment had no impact on intracranial bleeding (OR=1.53, 95%CI:0.71-3.29, p=0.2765) and gastrointestinal bleeding (OR=1.35, 95%CI:0.91-1.99, p=0.1331).

Conclusion
In Taiwan, patients with AF were treated with low guideline-adherent rate in anti-thrombotic therapy. However, undertreatment only resulted in increasing mortality rather than thromboembolic events. Therefore, it is suggested that application of the guideline on anti-thrombotic therapy require further investigation and justification.
第一篇、心房顫動病患使用抗血栓劑符合準則與否和心血管事件發生關聯性之探討 1
第一章 研究背景 1
第二章 文獻回顧 3
第一節 心房顫動疾病簡介 3
2.1.1 流行病學 3
2.1.2 心房顫動分類 4
2.1.3 致病機轉與相關因素 5
2.1.4 臨床症狀與併發症產生原因 6
2.1.5 治療方式 7
第二節 心房顫動病患抗血栓劑的選擇比較 13
2.2.1 抗血栓劑個論 13
2.2.2 抗血栓劑在心房顫動患者的臨床試驗綜合比較 16
第三節 中風危險性評估與準則建議 34
第四節 Warfarin出血危險性的考量 38
2.4.1 出血危險性評估方法 38
2.4.2 選擇適當的INR值 40
2.4.3 正確的warfarin使用方式 41
2.4.4 抗凝血劑用藥品質的重要性 42
第五節 Warfarin於臨床上應用的現況 48
2.5.1 Warfarin處方率及影響因素為何? 48
2.5.2 沒有使用warfarin族群的預後 49
2.5.3 臨床試驗的結果是不是可以直接應用在臨床上? 50
第三章 研究目的 52
第四章 研究方法 53
第一節 研究設計 53
4.1.1 研究類型 53
4.1.2 研究材料與工具 53
4.1.3 納入對象 54
4.1.4 排除標準 54
4.1.5 栓塞危險分級 55
4.1.6 Warfarin禁忌症 55
4.1.7 抗血栓劑 55
4.1.8 準則符合情形 56
4.1.9 研究事件 57
第二節 研究變項及操作定義說明 60
第三節 資料處理流程 64
4.3.1 檔案串聯 64
4.3.2 研究流程…………………………………………………………….65
第四節 統計方法 66
4.4.1 統計工具 66
4.4.2 統計模式設定 66
4.4.3 資料分析方法 66
第五章 研究結果 68
第一節 病患基本特性分佈 68
第二節 抗血栓劑處方型態與準則一致性 69
5.2.1 抗血栓劑處方型態 69
5.2.2 不同栓塞危險性下與準則符合之情形 69
5.2.3 不同準則符合情形下的病患特性 69
第三節 心血管事件及死亡預測因子 71
5.3.1 不同準則符合度與心血管事件及死亡的關聯性 71
5.3.2 其他心血管事件預測因子 71
5.3.3 栓塞危險性與心血管事件及死亡的關聯性 72
第六章 研究討論 83
第一節 研究族群人口特性 83
第二節 抗血栓劑處方型態與準則一致性評估 87
6.2.1 Warfarin處方型態 87
6.2.2 準則符合情形評估 89
第三節 心血管事件發生與準則一致性的關聯探討 98
6.3.1 與 Nieuwlaat等人的研究結果比較 98
6.3.2 以ACC/AHA/ESC(2006)準則重新評估 99
6.3.3 Warfarin禁忌症與符合準則定義的問題 100
6.3.4 臺灣心房顫動病患缺血性中風機率 100
6.3.5 Warfarin平均處方日劑量 101
6.3.6 準則預測性 103
第四節 心血管事件的其他預測因子 117
6.4.1 栓塞性事件 117
6.4.2 出血性事件 117
6.4.3 次要研究事件:死亡 118
第五節 研究限制 120
第七章 結論與建議 121
第八章 未來研究方向 122

第二篇、臨床藥事服務- Warfarin (可邁丁)之用藥衛教 123
第一章 服務背景 123
第二章 衛教方法 124
第三章 衛教結果 126
第四章 心得與建議 129
參考文獻 …………………………………………………………………………….131
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