心房顫動病人之心律控制藥物治療與中風風險之探討

Rhythm Control Therapy and Risk of Stroke in Patients with Atrial Fibrillation: A Nationwide Retrospective Cohort Study in Taiwan

王昱文(Yu-Wen Wang)

指導教授 ： 林珍芳

國立臺灣大學/醫學院/臨床藥學研究所/碩士(2016年)

https://doi.org/10.6342/NTU201601537

摘要

研究背景：
心房顫動是造成缺血性中風的一個顯著危險因子，而心律控制(rhythm control)藥物可以改善心房顫動病人的症狀，然而過去針對心律控制藥物的研究多為比較其矯正心律的能力，但直接比較不同心律控制藥物對於心房顫動（AF: atrial fibrillation）病人在後續發生中風風險的差異尚未有充分的探究。

研究目的：
針對沒有結構性心臟病的新診斷心房顫動病人，使用不同種類心律控制藥物對於後續發生中風的風險是否有顯著不同。

研究方法：
本研究為回溯性世代研究（retrospective cohort study），以2005-2011年的臺灣健康保險資料庫做為資料來源，篩選新診斷且沒有結構性心臟病的心房顫動病人。根據病人在心房顫動診斷後第一次使用之心律控制藥物分組，並挑選出使用amiodarone以及propafenone的病人做為主要研究族群。同時為了減少選擇性偏差，也利用傾向分數（propensity score）進行比較組間的配對，建構類似隨機分派對照實驗（randomized controlled trial），最後以Cox proportional hazards regression model進行中風風險之分析。

研究結果
台灣在非結構性心臟病的新診斷AF病人中，最常使用的口服心律控制藥物為amiodarone，使用amiodarone的病人相較於使用propafenone的病人，有統計上顯著較高發生中風事件的風險。（HR =1.19; 95% CI:1.01 - 1.41; P=0.0435）。同時也發現在未併用口服抗凝血劑的次族群中有統計上顯著的差異（HR = 1.28; 95% CI:1.03-1.58; P=0.0245）。此外也發現在30天 (HR =2.28; 95% CI:1.33-3.918; p-value=0.0027)、60天 (60-day period : HR= 2.267; 95% CI:1.415-3.633; p-value=0.007)、90天 (90-day period : HR=2.385; 95% CI: 1.577-3.607; p-value<0.0001)與180天 (180-day period : HR=2.116; 95% CI:1.515-2.957; p-value<0.0001) 的追蹤期間內，皆有統計上顯著較高的中風發生風險。

結論
本研究發現對於沒有結構性心臟病的心房顫動病人，使用amiodarone相較於使用propafenone有較高的中風發生風險。在未併用口服抗凝血劑的心房顫動病人以及用藥後短期內，又有更加顯著的差異。

關鍵字

心房顫動 ； 心律控制 ； amiodarone ； propafenone ； 中風

並列摘要

Background
Atrial fibrillation (AF) is a significant risk factor for ischemic stroke. Rhythm control is an important treatment strategy which can significantly improve patients’ symptoms. However, the comparative effectiveness of rhythm control agents of risk of stroke in patients with AF remains unknown.

Purpose
To evaluate the comparative effectiveness of rhythm control agents on risk of stroke in patients with AF.

Methods
This study is a retrospective cohort study based on National Health Insurance Research Database (NHIRD) from 2005 to 2011. Newly diagnosed AF withoutstructural heart disease patients are included and grouped by type of rhythm control agent first prescribed following AF. To reduce selection bias, a propensity score matching approach was used to create matched cohorts similar to randomized controlled trial. Patients used amiodarone and propafenone are the main population this study focus on. Cox proportional hazards regression model was performed to estimate the risk of stroke in patients with AF.

Results
Among all the rhythm control agents, amiodarone remains the most frequently prescribed drug in Taiwan. After comparing amiodarone with propafenone, the application of amiodarone holds higher risk of stroke events in AF patients (HR=1.189; 95% CI: 1.005 - 1.406; P=0.0435). This result is similar in the subgroup which patients were not prescribed with oral anticoagulants (HR=1.276; 95% CI: 1.032 - 1.579; P=0.0245). Also, our results implied that there may have a higher risk which amiodarone were used to restore sinus rhythm in 30, 60, 90 and 180 days of follow up time period.

Conclusion
AF patients without structural heart disease who applied propafenone seems to have a lower risk on the occurrence of stroke events compared with patients used amiodarone. This effect was more significant in short-term period after amiodarone were used.

並列關鍵字

atrial fibrillation ； rhythm control ； amiodarone ； propafenone ； stroke

參考文獻

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4. January CT, Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: Executive Summary. A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society 2014;130:2071-104.

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