臺灣心房顫動患者抗凝血劑使用現況及預測因子

Predictors and Patterns of Warfarin and Non-vitamin K Antagonist Oral Anticoagulation (NOAC) Use in Patients with Atrial Fibrillation in Taiwan

胡慕美(Mu-Mei Hu)

指導教授 ： 林慧玲

共同指導教授 ： 林珍芳(Zhen-Fang Lin)

國立臺灣大學/藥學專業學院/臨床藥學研究所/碩士(2015年)

https://doi.org/10.6342/NTU.2015.11176

摘要

背景：
心房顫動 (atrial fibrillation; AF) 為臨床上常見之心律不整，且為中風的危險因子。過去治療準則建議使用抗血栓劑 (包含抗血小板劑以及抗凝血劑) 預防中風，其中抗凝血劑僅有warfarin可使用。過去文獻指出實際上使用抗血栓劑的比例偏低，warfarin的使用比例低於三成。目前新一代口服抗凝血劑 (Non-vitamin K antagonist oral anticoagulation; NOAC) 包括dabigatran、rivaroxaban、apixaban已在臺灣上市，國際治療準則也建議這些藥品為warfarin之外的替代選項。

目的：
目前臺灣仍缺乏NOAC的相關研究，藥品上市後的臨床使用情況仍然所知有限。本研究的目的為分析NOAC在臺灣的使用現況及其預測因子。

研究方法：
本研究屬於回溯性觀察研究，分析民國96年1月1日至102年12月31日臺大醫院門診、住院、急診出現至少三次AF診斷 (ICD-9 CM code 427.31) 的非瓣膜性AF病人。研究主要分成兩個部分：
(一) 觀察目前NOAC和warfarin的使用情況
(二) 開方因子分析：找出是否使用抗凝血劑、抗凝血劑使用種類、從warfarin換藥至NOAC的可能影響因素。使用多變項羅吉斯複迴歸模式分析可能影響開方的因子。

結果：
最終納入3662位病人，平均年齡為69歲，主要分布在大於等於75歲的年齡層 (38.6%)，女性病人較少 (45.5%)。平均CHADS2 score為1.4分、CHA2DS2-VASc score 2.8分、HAS-BLED score為2.0分。高血壓是病人最常見的共病，比例為52.1%，其次為缺血性心臟病 (27.4%)、糖尿病 (20.8%)、血脂異常 (19.2%)。在1215位使用抗凝血劑的病人中有23.6% 使用NOAC，76.4%使用warfarin。在研究期間，warfarin的使用情況呈現減少趨勢，而NOAC則呈現增加趨勢。依據目前治療準則的建議，我們發現本研究CHA2DS2-VASc score兩分以上的病人，32.48%使用抗凝血劑，以warfarin使用者為主 (71.3%)、dabigatran次之 (26.03%)，rivaroxaban最少 (2.67%)，未使用抗凝血劑的比例有67.52%。於CHA2DS2-VASc score一分以上的病人，也有類似的結果。

開方因子分析部分，中風或栓塞史、降血壓藥品、糖尿病藥品、減少出血風險藥品的使用會增加抗凝血劑使用機會，女性、高血壓、缺血性心臟病、癌症、肝疾病、腎疾病、出血史、aspirin使用則降低抗凝血劑的開方機會。年齡增加、缺血性心臟病、糖尿病、肥厚性心肌病變、周邊血管疾病、癌症、失智症、aspirin使用會增加NOAC開方機會，肝疾病、腎疾病、中風或栓塞史則降低NOAC開方機會。年齡增加會增加warfarin換藥至NOAC的機會，腎疾病、出血史則降低換藥機會。

結論：
本研究提供目前臺灣NOAC在臺大醫院的使用現況。我們發現AF病人使用NOAC的比例正在增加，而warfarin的比例正在下降。和現行治療準則對照，在建議使用抗凝血劑的族群實際用藥的比例約在32.5%。中風及栓塞史會增加抗凝血劑開方機會，然而易增加出血風險的共病則減少抗凝血劑開方。健保給付規範在本研究可能影響抗凝血劑使用的種類。年齡增加的warfarin使用者有較大機會換藥至NOAC，腎疾病及有出血史病人較不會換藥。

關鍵字

心房顫動 ； 新一代口服抗凝血劑 ； 中風

並列摘要

Background :
Atrial fibrillation (AF) is one of the risk factors for ischemic stroke. In the past, warfarin had been the drug of choice for pharmacological stroke prevention in AF, especially for those at higher risk of stroke. Previous literatures showed low prescription rate for warfarin in AF patients. Non-vitamin K antagonist oral anticoagulation (NOAC) agents have been approved by FDA for stroke prevention as alternatives to warfarin in non-valvular AF patients and have been available in Taiwan since 2012. So far, there is limited real-world data on how NOAC agents are currently being used and whether current treatment guidelines are followed among health care professionals in Taiwan.

Objectives :
We aim to provide answers to the following topics :
(1) Patterns of anticoagulants utilization in Taiwanese AF patients
(2) Factors driving the initiation of anticoagulant treatment (no anticoagulant treatment vs. anticoagulant use) and the selection of and switching between different anticoagulants (warfarin or NOAC).

Methods :
We used National Taiwan University Hospital (a 2500-bed tertiary medical center) electronic database to include all non-valvular AF patients from 1 January 2007 to 31 December 2013. Multivariate logistic regression models were used to examine factors driving the initiation of anticoagulant treatment and the selection of and switching between different anticoagulants.

Results :
Of 3662 patients identified in our study, the average age was 69 years, 38.6% of patients were aged ≥ 75 years and 45.5% were female. Among study population, hypertension was the most common comorbidities (52.1%) and 27.4% had ischemic heart disease, 20.8% had diabetes and 19.2% had dyslipidemia. Of 1215 anticoagulant users, 23.6% and 76.4% were on NOAC and warfarin, respectively. Nearly 32.5% patients with CHA2DS2-VASc score ≥ 2 were on anticoagulant according to current treatment guideline. Among these users, 71.3% and 28.9% were on warfarin and NOACs, respectively. Similar trends were found in patients with CHA2DS2-VASc score ≥ 1.

Patients with female gender, hypertension, ischemic heart disease, cancer, hepatic disease, renal disease, bleeding history, aspirin use were less likely to be anticoagulant user while more likely with stroke history (OR 2.64, 95% CI 2.02 to 3.45). Older age, ischemic heart disease, diabetes, peripheral vascular disease were some of the factors associated with NOAC use while hepatic and renal disease showed the opposite results (OR for hepatic disease 0.34, 95% CI 0.12 to 0.99; OR for renal disease 0.27, 95% CI 0.10 to 0.73). Among 928 warfarin users, 18.9% switched to NOAC during study period. Warfarin users with older age were more likely to switch to NOAC and less likely with renal disease and bleeding history (OR for renal disease 0.16, 95% CI 0.04 to 0.69; OR for bleeding history 0.33, 95% CI 0.12 to 0.93).

Conclusion :
Our study provides current patterns of anticoagulant utilization in National Taiwan University Hospital. Among patients initiated anticoagulant treatment, 23.6% used NOAC instead of warfarin. During study period, the prescription rate for NOAC was rending up and in warfarin user we found the opposite trend. Nearly 32.5% patients received anticoagulant prescription according to current treatment guideline. Stroke history was associated with anticoagulant use while comorbidities associated increased bleeding risk showed opposite result. NHI Prescribing recommendations for NOAC may affect the selection for anticoagulants. Warfarin users with older age were more likely to switch to NOAC, whereas renal disease and bleeding history were less likely associated with switching.

並列關鍵字

atrial fibrillation ； Non-Vitamin K antagonist oral anticoagulation ； NOAC

參考文獻

參考文獻

1. Hsieh FI, Lien LM, Chen ST, et al. Get With the Guidelines-Stroke performance indicators: surveillance of stroke care in the Taiwan Stroke Registry: Get With the Guidelines-Stroke in Taiwan. Circulation 2010;122:1116-23.

2. Sanoski CA, Bauman JL. The Arrhythmias. Pharmacotherapy: A Pathophysiologic Approach, 8 th ed New York: McGraw-Hill; 2011:273-94.

3. Lee CH, Liu PY, Tsai LM, et al. Characteristics of hospitalized patients with atrial fibrillation in Taiwan: a nationwide observation. Am J Med 2007;120:819 e1-7.

4. Chien KL, Su TC, Hsu HC, et al. Atrial fibrillation prevalence, incidence and risk of stroke and all-cause death among Chinese. Int J Cardiol 2010;139:173-80.