老年人使用支氣管擴張劑與心房纖維顫動相關性之研究：一人群基礎縱斷世代研究

The Association between Bronchodilators use and new-onset atrial fibrillation: A population-based longitudinal cohort study

林素美(Su-Mei Lin)

指導教授 ： 陳永福

中山醫學大學/健康管理學院/國際健康產業經營管理碩士在職專班/碩士(2021年)

https://doi.org/10.6834/csmu202100051

摘要

心房纖維顫動 (atrial fibrillation, AF) 是臨床上最常見的心律不整疾患，而AF是缺血性中風的主要危險因子之一，AF導致之缺血性腦中風經常造成嚴重的神經學症狀，甚至導致死亡，因而耗費龐大的社會成本，然而，隨著年齡增長，發生率亦逐年增加，因此成為國家與衛生部門重大的議題。
本研究欲朝此方向探討，深入了解整體支氣管擴張劑在慢性肺阻塞疾病病人與新生心房纖維顫動之間所帶來的影響。因此本研究希望藉由使用國家衛生研究院(National Health Research Institute)提供之百萬歸人抽樣檔(2010年承保抽樣歸人檔; Longitudinal Health Insurance Database 2010;LHID2010)之資料以世代追蹤研究方法分析十二年間台灣地區使用支氣管擴張劑與心房纖維顫動之相關性。
本研究追蹤時間為12年，為了處理有關推論的偏誤與觀察的時間，就是所謂不死的時間偏誤(immortal time bias)，我們以用藥時間分佈來進行配對Prescription time-distribution matched (PTDM)，結果發現以年齡、性別進行使用與沒有使用支氣管擴張劑藥物組的1比2配對的研究，在11,950位支氣管擴張劑藥物使用者中，有877位發生新生心房纖維顫動，每10,000 person-months發生率為8.22。粗估危險比（crude hazard ratio, HR）是1.527(1.397-1.669)。經過校正調整共病症與併用藥物等因子後，支氣管擴張劑藥物使用者的新生心房纖維顫動發生風險會顯著高於沒有使用氣管擴張劑藥物者（aHR 1.266，95％CI : 1.151-1.392，P <0.0001）。同時性別上發現不論男女性，使用支氣管擴張劑藥物者的新生心房纖維顫動發生風險會明顯高於未使用支氣管擴張劑藥物者。本研究另外以傾向分數配對方法，進行使用與沒有使用支氣管擴張劑藥物組的1比1配對研究，結果發現在10,482位慢性肺阻塞疾病病人的支氣管擴張劑藥物使用者中，有1,685位發生新生心房纖維顫動，經過校正調整共病症與併用藥物等因子後，支氣管擴張劑藥物使用者的新生心房纖維顫動發生風險會顯著高於非支氣管擴張劑藥物使用者（aHR 1.239，95％CI : 1.081-1.421，P = 0.0002）。
本研究以追蹤世代研究方法，分析十二年台灣全民健保資料庫中支氣管擴張劑藥物與新生心房纖維顫動之相關性，建議如果長期使用支氣管擴張劑藥物，可能會增加台灣人24-26% 心房纖維顫動的發生比率；在男女性別上都看到類似的結果。本研究結果與一些文獻的結果有一致性，可作為臨床醫師使用支氣管擴張劑藥物時之參考依據。未來仍需要執行前瞻性的隨機對照試驗來驗證支氣管擴張劑藥物對新生心房纖維顫動的風險性，同時進一步研究支氣管擴張劑藥物增加新生心房纖維顫動的機轉關係。

關鍵字

支氣管擴張劑 ； 心房纖維顫動

並列摘要

Several observational cohort and meta-analytical studies in humans have shown that bronchodilators users have a higher risk of atrial fibrillation than nonusers. However, some studies including randomized clinical trials have the opposite results. This study aimed to investigate the association between bronchodilators and new-onset atrial fibrillation in Taiwan.
In a nationwide retrospective population-based cohort study, 11,950 subjects having received bronchodilators therapy (bronchodilators -users) since January 1 2002, and observed through December 31 2013 were selected from the National Health Insurance Research Database of Taiwan. Likewise, use Prescription time-distribution matching (PTDM) method 23,900 patients had no bronchodilators therapy (bronchodilators -non-users) were included as controls in this study. Multivariable Cox proportional hazards analysis for drug exposures was employed to evaluate the association between bronchodilators treatment and new-onset of atrial fibrillation risk. We also used the Kaplan–Meier method and the long-rank test to evaluate the difference of probability of dementia-free survival.
During the 12-year follow-up period, 877 of all enrolled subjects (Incidence rate of atrial fibrillation: 8.22 per 10,000 person-months) developed atrial fibrillation. Overall, bronchodilators therapy increased the risk of new-onset atrial fibrillation by 26% (adjusted hazard ratio [HR] 1.266，95％CI : 1.151-1.392，P <0.0001）. A 1:1 matching propensity score method was also used to match 10,482 patients to 10,482 controls in the non-bronchodilator group for analysis. The bronchodilator group was associated with a higher risk of new-onset atrial fibrillation (aHR 1.239，95％CI : 1.081-1.421，P = 0.0002).
In this population-based cohort study, we found that bronchodilators use is associated with an increased risk of atrial fibrillation. Risk of incident atrial fibrillation should be considered when weighing the benefits and risks of bronchodilator treatment in patients with chronic obstructive pulmonary disease or asthma in clinical practice. Further basic study is needed to search the underlying mechanism of association between bronchodilators and new-onset atrial fibrillation in futhure.

並列關鍵字

Brochodilators ； atrial fibrillation

參考文獻

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