抗血栓藥物使用於發生急性冠心症或施行經皮冠狀動脈介入術後且併有心房顫動病人之用藥模式研究與療效、安全性評估

Treatment Patterns and Outcomes Study of Antithrombotic Use in Atrial Fibrillation Patients Presenting with Acute Coronary Syndrome or Percutaneous Coronary Intervention

王悅心(Yueh-Hsin Wang)

指導教授 ： 林芳如

國立臺灣大學/醫學院/臨床藥學研究所/碩士(2017年)

https://doi.org/10.6342/NTU201703850

摘要

研究背景
中風的預防是面對心房顫動病人時最重要的議題，目前口服抗凝血藥品（oral anticoagulant）為最有效的預防策略。然而，多數病人可能同時有冠狀動脈疾病的共病症，若發生急性冠心症或接受經皮冠狀動脈介入治療術後，則需使用雙重抗血小板藥品來預防心肌梗塞或支架栓塞的發生。此類病人在同時有使用口服抗凝血藥物及雙重抗血小板藥物的適應症之下，如何平衡栓塞與出血的風險以決定抗血栓藥品的使用一直是臨床上的一大難題。目前多數研究的結果並不一致，且僅有少數研究目標族群以亞洲人為主，過去文獻顯示亞洲人相較於高加索人種有較高的顱內出血傾向，因此亟需以實證資料以確認如何給予有效且具安全性的抗血栓藥物組合。
研究目的
欲了解臺灣心房顫動病人在急性冠心症或經皮冠狀動脈介入治療術後抗血栓藥物使用模式，並比較不同療法之間的療效及安全性。
研究方法
本研究為一回溯性世代研究，利用臺大醫院整合型資料庫納入在2008/1/1至2016/4/1間發生急性冠心症或接受經皮冠狀動脈介入治療術的心房顫動病人，以出院所使用的抗血栓藥物組合做為研究分組，分別為雙重抗血小板藥物、三重抗血栓藥物、雙重抗血栓藥物、單一抗血小板藥物及單一抗凝血藥物組別，以傾向分數（propensity score）及治療權重倒數機率（inverse probability of treatment weighting, IPTW）方法校正組間的基線差異後，進一步以Cox比例風險模式及實際治療分析（as-treated）方式分析各組在用藥期間發生主要不良心腦血管事件（major adverse cardiac and cerebrovascular event, MACCE）及出血事件的差異，並進行敏感性分析。
研究結果
本研究共納入719位發生急性冠心症或接受經皮冠狀動脈介入治療術的心房顫動病人，其入院前抗血栓藥物的使用以抗血小板藥物為主，出院後則以雙重抗血小板藥物為最常使用的抗血栓藥物組合（53.3%），其次為單一抗血小板藥物（23.9%）、三重抗血栓藥物（11.1%）、雙重抗血栓藥物（9.6%）及單一抗凝血藥物（2.1%）。由於樣本數限制，我們僅比較雙重抗血小板藥物、三重抗血栓藥物、雙重抗血栓藥物以及單一抗小板藥物組。各組在主要不良心腦血管事件的追蹤時間中位數分別為133天、31天、280天及149天，各組出血事件的追蹤時間中位數則大致與不良心腦血管事件的追蹤時間中位數相同。整體來說，多數事件發生於出院後六個月內，不良心腦血管事件發生率在本研究為11.4每100人年，而任何出血事件的發生率則為25.9每100人年。在主要不良心腦血管事件的比較上，各組與雙重抗血小板藥物相較無顯著差異，而在出血事件的比較中，雙重抗血栓藥物相較於雙重抗血小板藥物在任何出血上有較低的風險（aHR, 0.20 [95% CI, 0.06-0.75]）。
結論
在心房顫動且發生急性冠心症或接受經皮冠狀動脈介入治療術的病人中，以雙重抗血小板藥物為最常使用的抗血栓藥物組合。此外，各組合在療效方面並無顯著差異，在安全性方面則以雙重抗血小板相較於雙重抗血栓藥物可能有較高的出血風險。惟本研究受限於樣本數較小，仍需要未來較大型的研究證實此發現。

關鍵字

抗血栓藥物 ； 心房顫動 ； 急性冠心症 ； 經皮冠狀動脈介入治療術

並列摘要

Background/ Objective
Stroke prevention is fundamental in the management of atrial fibrillation (AF), and oral anticoagulant (OAC) is the most effective prevention strategy. However, some of AF patients are comorbid with coronary artery disease and might present with acute coronary syndrome (ACS) or receive percutaneous coronary intervention (PCI). Dual antiplatelet therapy (DAPT) is the recommended antithrombotic regimen to prevent myocardial infarction or stent thrombosis after ACS or PCI. Whether to use triple therapy (OAC plus DAPT) to prevent thrombotic events in these patients is controversial due to possibly excessive bleedings. There remains insufficient evidence to determine the optimal antithrombotic strategy, especially in the Asian population. This study aimed to examine the real-world treatment patterns of antithrombotic use among these patients and compare the effectiveness and safety of different antithrombotic regimens.
Methods
A retrospective cohort study was conducted at the National Taiwan University Hospital (NTUH). AF patients undergoing a new ACS or PCI during 2006/1/1-2016/4/1 were enrolled. Antithrombotic regimens were classified into DAPT (the reference group), triple therapy (TT), dual therapy (DT), single antiplatelet therapy (SAPT), and single oral anticoagulant (SOAC). Outcomes of interest included major adverse cardiac and cerebrovascular event (MACCE) and any or major bleeding defined by the PLATO criteria. Propensity score and inverse probability of treatment weighting (IPTW) were used to balance the baseline characteristics among comparison groups. The treatment effect was estimated using Cox proportional hazards model with as-treated approach. A series of sensitivity analyses were also conducted.
Results
In this study, a total of 719 AF patients presenting with ACS or PCI were included. The use of oral anticoagulant was relatively low at baseline. At the discharge from the index hospitalization for ACS or PCI, DAPT was the most common antithrombotic therapy (53.3%), followed by SAPT (23.9%), TT (11.1%), DT (9.6%), and SOAC (2.1%). Due to the sample size limitation, we only compared TT, DT, and SAPT to DAPT. The median follow-up for MACCE was 133 days in the DAPT group, 31 days in the TT group, 280 days in the DT group, and 149 days in the SAPT group. The median follow-up duration for any bleeding was similar to that for MACCE, but slightly shorter. Most MACCEs and bleeding events were within six months after index hospitalization. The overall incidence rate for MACCE was 11.4 per 100 person-years in the included patients, and 25.9 for any bleeding. No significant difference in MACCE was found among the different antithrombotic regimens. DT, compared to DAPT, was associated with a lower risk of any bleeding (aHR, 0.20 [95% CI, 0.06-0.75]) in the main analysis.
Conclusions
In AF patients presenting with ACS or PCI, DAPT was the most commonly prescribed antithrombotic regimen for cardio-cerebrovascular disease prevention. Effectiveness outcomes were comparable across different antithrombotic strategies, but the sample size was relatively limited. The increased bleeding risk with DAPT compared with DT warrants further investigation.

並列關鍵字

Antithrombotic use ； atrial fibrillation ； acute coronary syndrome ； percutaneous coronary intervention

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