研究背景與目的
慢性心衰竭（Chronic heart failure，簡稱CHF）是一種在老年人身上常見之慢性疾病。由於人口結構的老化以及對各種心臟疾病存活率的提高，心衰竭病患在近年有十足的成長，而在臺灣這也成為一個顯著的健康問題，根據衛生福利部中央健康保險署之統計在2014年約有大於22,000之病患因為心衰竭而住院
Ivabradine是目前用於治療慢性心衰竭的藥物之一。其療效主要由一篇國外之臨床試驗所證實，能夠減少病人因心衰竭而再住院。然而，在一篇臺灣心衰竭病人的世代研究中可以得知，與其他國家相比臺灣之族群明顯有較高之再住院率。又目前並沒有ivabradine用於本土之相關研究以證實其結果能外推到臺灣之族群上。
基於臺灣心衰竭病人的高再住院率與缺少國內ivabradine之使用資料，本研究希望藉由分析心衰竭病人使用ivabradine與因心衰竭再住院發生率，提供相關資料以供臨床照護之參考依據。

研究方法
本研究以病歷回顧 (chart review) 方式進行台灣單中心、回溯性世代研究 (retrospective cohort study)，資料來源為成大醫院提供之2013年至2018年之病歷資料。研究對象為20歲（含）以上且於2013至2018年間診斷為心衰竭之病人，且符合左心室收縮分率 (left ventricular ejection fraction, LVEF) 小於等於35%及心跳大於等於每分鐘75下。依據ivabradine引進成大醫院之時間點分成前後兩個時期，有使用ivabradine之組別為研究組，尚無ivabradine而接受傳統治療的組別為對照組，採治療意向（intention-to-treat，簡稱ITT）設計，至多追蹤1年，觀察兩組發生因心衰而再住院之事件，並以多變項Cox比例風險模型校正干擾因子，計算風險比。本研究亦執行若干敏感性分析，包含：根據治療（as-treated，簡稱AT）設計、加入時間參數進行校正以及校正競爭風險因子。
研究結果
本研究共收錄115位新使用ivabradine、134位接受傳統治療之心衰竭病人。Ivabradine組有24人在指標日期時為住院病人 (急性失償性心衰竭病人)，而Active comparison組則全為門診病人，其餘在性別、年齡、抽菸、BMI及追蹤天數，兩組皆無顯著差異。整體而言，兩組的共病症與用藥史盛行率相似。本研究結果顯示Ivabradine組病人比起Active comparison組有顯著較低的一年內因心衰竭而再住院發生風險（19.1% vs. 31.3% ; adjusted HR 0.487, 95% CI 0.274-0.866）。在次要結果部份，經過一年之追蹤，ivabradine之使用主要能夠下降病人之心跳，而在左心室收縮分率、背景所使用之利尿劑日劑量等臨床參數改變上，兩組之間並無太大之差異。另外，急性失償性心衰竭病人使用ivabradine在本研究中並無發生嚴重之不良反應事件。敏感性分析結果：AT設計下，分析結果一致（19.1% vs.31.3%; adjusted HR 0.511, 95% CI 0.287-0.911）；經過年份之校正後，分析結果亦一致（adjusted HR 0.285, 95% CI 0.084-0.969）。

結論
本研究觀察到臺灣心衰竭病人符合LVEF ≤35%以及心跳≥75bpm使用ivabradine發生因心衰竭再住院的風險低於未使用的病患，因此本研究建議在符合上述條件之心衰竭病人皆應該使用ivabradine。另外，急性失償性心衰竭病人使用ivabradine在本研究中並無發生嚴重之不良反應事件，因此，有關於急性失償性心衰竭病人是否應該使用ivabradine是需要更多的討論以及大型的研究來證實其安全性和療效。

Objective:
Ivabradine is a pure HR-lowering agent reported to reduce rehospitalization rate due to heart failure in a clinical study. According to the rehospitalization rate was much higher in Taiwanese population than western countries among heart failure patients and the effectiveness of ivabradine still remains unknown. Thus, the aim of this cohort study was to estimate the association between ivabradine use and rehospitalization rate due to heart failure in Taiwan.

Methods:
We conducted a retrospective cohort study with historical control by using chart review in the National Cheng Kung University Hospital (NCKUH). We identified ivabradine users and ivabradine non-users during study period. All participants were adults (≥ 20 years old) with LVEF≤35% and heart rate≥75bpm from 2013 through 2018, and followed up until rehospitalization due to heart failure or end of 1-year follow up. We estimated the HR from Cox proportional hazard models of rehospitalization among ivabradine users, as compared with non-users.

Results:
We identified ivabradine users (n = 115) from 2016 through 2018 and non-users (n = 134) from 2013 through 2015. In general, ivabradine users had a similar prevalence of comorbidities and medication history with non-users. The result of primary outcome showed that ivabradine users has a decreased risk of rehospitalization due to heart failure than non-users (19.1% vs. 31.3%; adjusted HR 0.487, 95% CI 0.274-0.866); In sensitivity analysis with as-treated design, the result was consistent (19.1% vs. 31.3%; adjusted HR 0.511, 95% CI 0.287-0.911).

Conclusion: Our study showed that the use of ivabradine associates with lower risk of rehospitalization due to heart failure among heart failure patients with LVEF≤35% and heart rate≥75bpm in Taiwan.

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