新診斷高血壓病人使用固定複方與單方併用降血壓 藥物之順從性及用藥型態分析

Adherence and Medication Utilization Patterns of Fixed-dose and Free Combination Anti-hypertensive Drugs among Newly Diagnosed Hypertensive Patients

許瀞尹(Chin-I Hsu)

指導教授 ： 沈麗娟

共同指導教授 ： 蕭斐元

國立臺灣大學/醫學院/臨床藥學研究所/碩士(2013年)

https://doi.org/10.6342/NTU.2013.10530

摘要

研究背景
高血壓及其相關的心血管併發症至今仍為造成人類死亡的主要原因之一。雖然已有許多高血壓藥物被證實可有效控制血壓並進一步預防心血管併發症的發生，目前全球高血壓病人的血壓控制率仍相當低落。而根據臨床實證，大部分的高血壓病人可能需要合併治療的藥物療程，在這樣的考量下，多重用藥的可能性升高，進而使得病人的服藥順從性降低，造成血壓控制目標較難達到。藉由固定複方之高血壓藥物減少藥物服用顆數，預期能因此增加病人之服藥順從性。由於服藥順從性會受到病人本身的共病症、服用其他藥品種類、人種以及相關健康保險制度的影響，因此在台灣的全民健保制度下，評估固定複方劑型是否具有相關好處是值得加以探討的議題。
研究目的
利用台灣全民健康保險資料庫分析新診斷高血壓病人，使用固定複方及單方併用之高血壓用藥 (ARB+thiazide利尿劑) 在服藥順從性及藥品持續持有天數比例於兩組間是否有所不同。
研究材料與方法
本研究為一回溯性世代研究，使用臺灣全民健康保險資料庫來進行分析。研究對象為2005年至2008年間新診斷高血壓且初次使用固定複方或單方合併之ARB+thiazide利尿劑的病人。主要研究終點則由第一次開方日期往後追蹤兩年的時間，計算病人的服藥順從性及藥品持續持有天數。
服藥順從性以藥品持有率作為代表：當藥品持有率≥80%時，定義為擁有良好的服藥順從性。藥品持續持有天數則是測量病人兩年內新開方日期至停止持有藥物的開方結束日期之時間。在統計分析方面，分別利用廣義線性模型及存活分析來評估固定複方劑型相較於單方併用療法對於服藥順從性及藥品持續持有比例的影響。此外，我們也利用邏輯迴歸分析及Cox比例風險迴歸來推測除了不同的用用型態外，其他可能影響服藥順從性及藥品持續持有比例的因子。
結果
2005年至2008年間，共有7348位新診斷高血壓病人並初次開始使用固定複方(Fixed-dose combination, FDC)與單方併用(Free combination, FC)之高血壓用藥(ARB+thiazide利尿劑)，其中屬於固定複方者有5725人(77.9%)，單方併用者1623人(22.1%)。除了患有腎臟疾病的比例(FDC v.s. FC, 3.5% v.s. 5.2%)及新開方日期前一年內用過的高血壓藥物種類在固定複方組顯著較少外，病人大部分的基本特性在兩組間均相似。在校正過其他可能影響結果的共變項後，使用固定複方劑型的病人，相較於單方併用組，無論何種時間切點，均有較高的藥品持有率(1 year, 52.58% v.s. 46.73%, p<0.0001; 2 year, 42.06% vs. 32.45%, p<0.0001)；有關於持續持有藥品，使用固定複方藥品可減低病人停止使用之風險約21% (HR 0.79, 95% CI=0.74-0.85)。新開方日期前一年使用過越多種高血壓藥物、併用降血醣藥物、新診斷六個月後方開始使用研究藥物、由醫學中心開方均為病人擁有良好服藥順從性及降低停止使用研究藥物比例的原因；罹有腎臟疾病及憂鬱症的病人則可能使服藥順從性不佳及增加停止使用藥物的風險。
結論
我們的研究發現，在兩年的追蹤時間裡，使用固定複方之高血壓用藥(ARB+thiazide利尿劑)確能增加新診斷高血壓病人的服藥順從性和藥品持續持有的人數比例。整體而言在本研究族群中，病人對於研究藥品的服藥順從性仍較為低落，我們也發現除了固定複方劑型外，其他可能影響服藥順從性的因素。本研究納入為新診斷高血壓之病人，兩年的觀察時間不足以瞭解使用固定複方者與預防相關心血管併發症發生的關聯性，因此仍需進一步臨床研究加以證實。

關鍵字

服藥順從性 ； 合併治療 ； 高血壓 ； 固定複方 ； ARB ； thiazide diuretic

並列摘要

Background
Until now, hypertension and its associated cardiovascular complications are still one of the major causes of death in the world. Despite many anti-hypertensive medications can prevent cardiovascular complications, the control rate of hypertension is still low around the world. Most hypertensive patients require combination therapy according to clinical evidences. Therefore, poor medication adherence would be a concern because of polypharmacy. Fixed-dose combination (FDC) is expected to improve patients’ adherence due to the decrease of pill burden. Since adherence to anti-hypertensive medications, an important factor for hypertension control, is influenced by patients’ co-morbidities, concurrent medications, ethnic populations and insurance policy, it is an important issue to investigate whether FDC has such benefit under Taiwan’s National Health Insurance (NHI) system.
Objective
The study aimed to compare the adherence and persistence among newly diagnosed hypertensive patients using fixed-dose combination (FDC) and free combinations (FC) of angiotensin receptor blocker (ARB)/ thiazide in Taiwan population.
Materials and Methods
This is a retrospective cohort study using the National Health Insurance Research Database (NHIRD) in Taiwan. Newly-diagnosed hypertensive patients who initiated FDC or FC of ARB/thiazide diuretic between 2005 and 2008 were identified from the NHIRD. Primary endpoint of our study was to analyze adherence and persistence of the study drug during 2 year follow-up. Adherence was measured by medication possession ratio (MPR) and persistence was defined as time from day of initiation to treatment discontinuation. General linear regression and Kaplan-Meier analyses were used to estimate the influence of FDC on adherence and persistence among hypertensive patients. Furthermore, we also used logistic regression model and Cox proportional hazard model to explore other predictors of adherence and persistence to study drugs.
Results
We identified 7348 newly-diagnosed hypertensive patients. Among them, 77.9% (n=5725) and 22.1% (n=1623) used FDC and FC of ARB/thiazide, respectively. Most demographic variables were balanced between the two groups, except for renal disease and anti-hypertensive prescriptions. After adjusting for covariates, in every different time period, patients in FDC group had higher MPR compared with FC group (1 year, 52.58% v.s. 46.73%, p<0.0001; 2 year, 42.06% vs. 32.45%, p<0.0001) and the likelihood of discontinuation of FDC therapy was significantly lower during 2-year follow-up period (HR=0.79, 95% CI=0.74-0.85). Moreover, higher adherence and lower likelihood of discontinuation of the study drug were observed in patients with previous use of anti-hypertensive therapy, anti-hyperglycemic agents, time lag between index diagnosis and index day more than 6 months, and managed at hospital center. On the contrary, having renal disease and depression increased rate of discontinuation and being low adherer.
Conclusions
Our findings suggest that use of FDC was associated with higher adherence and persistence rate than use of FC in newly-diagnosed hypertensive patients during 2-year follow-up period. The level of medication adherence to either FDC or FC was relative low in our study group. We also found several factors that may impact on medication adherence. However, we couldn’t conclude the potential clinical benefits associated with FDC of antihypertensive drug in newly diagnosed hypertensive patients during this 2-year follow-up period.

並列關鍵字

Patient adherence ； combination therapy ； hypertension ； fixed-dose combination ； angiotensin receptor blocker ； thiazide diuretic

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