利用大數據資料庫探討神經科常用藥物之成效及副作用

Explore the efficacy and side effects of common medications in clinical neurology – using national health registry and insurance data

張凱茗(Kai-Ming Jhang)

指導教授 ： 廖勇柏

中山醫學大學/健康管理學院/公共衛生學系博士班/博士(2018年)

摘要

本研究利用大數據資料庫探討神經科臨床上常用藥物的成效及副作用。研究分成兩大部分：第一部分探討頸動脈狹窄的病患接受頸動脈支架(carotid artery stenting)放置後，雙抗血小板藥物使用時間長短，對後續腦血管疾病發生率的影響。結果發現手術後使用較長期間(>6週)的雙抗血小板藥物對於術後腦中風的發生與使用4~6週相仿，並未降低術後6個月的缺血性中風發生率。第二部分探討鈣離子阻斷劑(Flunarizine及cinnarizine)引發動作障礙副作用的風險。結果發現使用Flunarizine及cinnarizine均顯著增加動作障礙的風險，HR分別是8.03 (95% CI 6.55-9.84) 及 3.41 (95% CI 2.50-4.63)。Flunarizine相關的動作障礙的危險因子包括高劑量及長時間的暴露、年紀越大、原發性顫抖或心血管疾病病史。臨床醫師在使用這些藥物時，必須更加權衡治療的好處及可能的副作用。

關鍵字

頸動脈支架 ； 抗血小板藥物 ； 椎體外症候群 ； 鈣離子阻斷劑 ； 健保資料庫

並列摘要

The present report use National Health Insurance Research Database (NHIRD) to explore the efficacy and side effects of common medications in clinical neurology. There are two main parts in this thesis. First part aimed to elucidate if long-term duration of aspirin and clopidogrel following carotid artery stenting (CAS) would provide an extra clinically relevant benefit. We concluded long-term (more than 42 days as compared with 30-42 days) use of aspirin plus clopidorel after CAS did not decrease the risk of ischemic stroke, composite vascular events or death during 6 months of follow up. The duration (1 month) suggested based on current guidelines is probably suitable. More researches are needed to provide more evidence on the appropriate duration of dual antiplatelet therapy after CAS. Second part investigated the incidence, occurrence time and risk factors of cinnarizine (cz) and flunarizine (fz)-related extrapyramidal side effects (EPSEs). The incidence rates of fz and cz-induced EPSEs were 21.03 and 10.3 per 10,000 person-months, respectively. The hazard ratios (HRs) of EPSEs among fz and cz subjects were 8.03 (95% CI 6.55-9.84) and 3.41 (95% CI 2.50-4.63) when compared with the control individuals. Higher exposure dose and duration, old age, history of essential tremor or cardiovascular disease increased the risk of fz-associated EPSEs. Potential risks should be weighed when considering long-term use of these drugs.

並列關鍵字

carotid artery stenting ； antiplatelets ； extrapyramidal syndrome ； flunarizine ； cinnarizine ； National Health Insurance Research Database

參考文獻

(一) 頸動脈狹窄的病患接受頸動脈支架(carotid artery stenting)放置後，雙抗血小板藥物使用時間長短，對後續腦血管疾病發生率的影響。

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