急性呼吸道感染與使用非類固醇消炎止痛藥對急性心肌梗塞發生風險的結合性效應：病例交叉研究

Joint Effect of Acute Respiratory Infection and Use of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) on Risk of Acute Myocardial Infarction：A Case-Crossover Study

溫燿駿(Yao-Chun Wen)

指導教授 ： 沈麗娟

共同指導教授 ： 蕭斐元(Fei-Yuan Hsiao)

國立臺灣大學/醫學院/臨床藥學研究所/碩士(2015年)

https://doi.org/10.6342/NTU.2015.10591

摘要

研究背景　
過去研究指出急性呼吸道感染會誘發急性心肌梗塞的發生，而非類固醇消炎止痛藥（nonsteroidal anti-inflammatory drugs, NSAIDs）亦會增加急性心肌梗塞發生的風險。臨床上醫師常處方NSAIDs藥品以緩解急性呼吸道感染病人相關症狀，不過目前沒有任何文獻同時探討此二因子之結合性效應對急性心肌梗塞風險的影響。
研究目的　
利用全民健康保險資料庫探討急性呼吸道感染與NSAIDs的使用對首次急性心肌梗塞的發生之結合性效應。
研究材料與方法
本研究為一病例交叉研究，以全民健康保險研究資料庫中2000、2005、2010年三個承保抽樣歸人檔（涵蓋人口約300萬人）為資料來源，選取2000-2011年間首次因急性心肌梗塞住院的病人做為病例，定義因急性心肌梗塞住院的日期為急性心肌梗塞發生日（index date），選取index date前1-7天為病例期（case period），index date前366-372天為對照期（control period），比較病例期與對照期中4種暴露情形（只有急性呼吸道感染、只有NSAIDs的使用、同時有此二暴露、完全沒有此二暴露）是否有差異。資料分析利用mutivariable conditional logistic regression進行勝算比（OR）的預測並校正病例期與對照期不一致的共病症與不一致的併用藥品。
研究結果　
本研究共分析3,019位首次急性心肌梗塞的病人。結果顯示在病例期同時有急性呼吸道感染及使用NSAIDs的病人、只有急性呼吸道感染的病人、只有使用NSAIDs的病人都較對照期多，在校正病例期與對照期不一致的共病症與不一致的併用藥品後，分別會增加4.78倍（95% CI: 3.32-6.89）、2.85倍（95% CI: 2.15-3.77）及1.61倍（95% CI: 1.33-1.95）急性心肌梗塞發生的風險。在次族群分析中，發現當有急性呼吸道感染時，使用注射劑型的NSAIDs、propionic acid derivatives類的NSAIDs及高劑量的NSAIDs風險較高。
結論　
本研究發現急性呼吸道感染與NSAIDs使用對急性心肌梗塞風險具有結合性效應，在有急性呼吸道感染的情況下，NSAIDs的使用會使得急性心肌梗塞風險提高，尤其是注射劑型的NSAIDs。

關鍵字

急性心肌梗塞 ； 急性呼吸道感染 ； 非類固醇消炎止痛藥(NSAIDs) ； 病例交叉研究 ； 全民健保資料庫

並列摘要

Background
Previous studies showed that acute respiratory infection would trigger acute myocardial infarction and use of nonsteroidal anti-inflammatory drugs (NSAIDs) was associated with an increased risk of acute myocardial infarction. In clinical practice, physicians usually prescribed NSAIDs for patients with acute respiratory infection to relieve symptoms. However, there is lack of studies focusing on the association between risk of acute myocardial infarction and NSAIDs use during acute respiratory infection.
Objective
To investigate the joint effect of acute respiratory infection and use of NSAIDs on risk of acute myocardial infarction by using the National Health Insurance Research Database in Taiwan.
Materials and Methods
We conducted a retrospective case-crossover study by using three sets of longitudinal health insurance database (LHID 2000, 2005, 2010) from Taiwan’s National Health Insurance Research Database. All patients who were first hospitalized due to acute myocardial infarction during 2000-2011 were enrolled for analysis. The date of first admission for acute myocardial infarction was defined as index date. The 1-7 days and 366-372 days prior to index date were defined as case and matched control period for each patient. We compared the following exposure status between case and control periods: acute respiratory infection without NSAIDs use, NSAIDs use without acute respiratory infection, both acute respiratory infection and NSAIDs use, neither acute respiratory infection nor NSAIDs use. Multivariable conditional regression models were used to estimate odds ratios adjusting discordant diagnoses of comorbidities and discordant use of concomitant medications.
Results
There were 3,019 newly diagnosed AMI hospitalized patients fulfilled the study criteria. In general, the risk of acute myocardial infarction is the highest in patients with acute respiratory infection and NSAIDs use (OR: 4.78, 95% CI: 3.32-6.89), and subsequently the odds ratios in patients with acute respiratory infection only and in patients with NSAIDs use only are 2.85 (95% CI: 2.15-3.77) and 1.61 (95% CI: 1.33-1.95), respectively. We found that parenteral NSAIDs, propionic acid derivatives of NSAIDs and high dose NSAIDs were associated with higher risk of acute myocardial infarction in patients with acute respiratory infection.
Conclusions
There was joint effect of acute respiratory infection and use of NSAIDs on risk of acute myocardial infarction. NSAIDs use was associated with increased risk of acute myocardial infarction in patients with acute respiratory infection, especially parenteral NSAIDs.

並列關鍵字

acute myocardial infarction ； acute respiratory infection ； nonsteroidal anti-inflammatory drugs(NSAIDs) ； case-crossover study ； National Health Insurance Research Database(NHIRD)

參考文獻

1. 民國102年死因統計年報. 2015. (Accessed July 14, 2015, at http://www.mohw.gov.tw/cht/DOS/DisplayStatisticFile.aspx?d=46319 s=1.)

2. Yeh RW, Sidney S, Chandra M, Sorel M, Selby JV, Go AS. Population Trends in the Incidence and Outcomes of Acute Myocardial Infarction. N Engl J Med 2010;362:2155-65.

3. Shanmugasegaram S, Dai S, Waters C. Incidence and Prevalence of Acute Myocardial Infarction in Canada. J Am Coll Cardiol 2015;65:A1385.

4. Dudas K, Lappas G, Stewart S, Rosengren A. Trends in out-of-hospital deaths due to coronary heart disease in Sweden (1991 to 2006). Circulation 2011;123:46-52.

5. Koopman C, Bots ML, van Oeffelen AA, et al. Population trends and inequalities in incidence and short-term outcome of acute myocardial infarction between 1998 and 2007. Int J Cardiol 2013;168:993-8.