Amiodarone 引起甲狀腺副作用之風險評估

Amiodarone為心律不整常用藥物，病人需要長期使用此藥物控制病情，但是相關副作用發生率很高，包括對甲狀腺的影響，使得臨床上藥物治療有所局限。本研究目的為探討影響amiodarone發生甲狀腺相關副作用的危險因子，應可幫助醫療人員做出最適合個別病人的藥物選擇以及訂定藥物安全性監測計畫。本研究收錄全部 2006 年 1 月至 2009 年 12 月在萬芳醫院接受門診治療，開始服用 amiodarone 有超過 3 個月之病人，觀察時間終止於2011年12月31日，每位病人至少都有兩年的觀察時間。本研究已通過臺北醫學大學暨附屬醫院聯合人體研究倫理委員會核准(TMU-Joint Institutional Review Board)案號：201111023。共169名研究對象符進行甲狀腺不良事件的危險因子研究，收集資料包括病人的基本資料與合併疾病、檢驗數值，與使用藥物品項與劑量等回顧研究，統計分析以邏輯式迴歸分析與分類樹迴歸分析，探討發生甲狀腺功能異常相關危險因子；並利用訂定著名Framingham Study risk score之方法，訂定一套使用amiodarone 引起甲狀腺不良事件發生之風險評估量表。並利用ROC( receicer-operating characteristic)曲線下面積(AUC)、敏感度(sensitivity)與特異度(specificity)確認本量表的檢測力。本研究發現基準期有監測TSH紀錄之病人共有115位(35%)，使用前三個月內有監測TSH記錄共有72位(22%)，一年內有TSH記錄有125位(38%)。邏輯式迴歸分析結果顯示甲狀腺不良事件危險因子包括：病人每公斤體重所使用amiodarone劑量較高及COPD，而amiodarone劑量較高、COPD與CKD的病人則是甲狀腺功能低下的危險因子。CART演算法分析結果顯示，以劑量3.419 mg/kg為切點，高於此劑量甲狀腺不良事件的發生率明顯較低劑量組高很多(15位vs 21位, 57.7% vs 30%)發生甲狀腺不良事件；在低劑量族群中有慢性腎臟疾病發生甲狀腺不良事件有10位(52.6%)明顯高於無慢性腎臟疾病之20位(16.1%)。本研究建立使用amiodarone 引起甲狀腺不良事件發生之風險評估量表，包括四項危險因子：劑量(mg/kg)、抽菸、COPD與CKD，ROC曲線下面積為0.8190，最佳切點為2分，因此，當風險評估量表總分高於2分，即屬於高危險族群。Kaplan-Meier 存活曲線分析兩組在各時間點之甲狀腺不良事件發生情形，高於2分組的發生不良事件比率明顯高得多(Log Rank test , p<0.001)。未來可考慮使用大型資料庫如：健保資料庫、台灣地區慢性腎衰竭登錄系統…等，確認本研究之結果。亦可研究藥師介入病人amiodarone的成效，做為將來推廣藥師介入的依據。

關鍵字

藥物引起甲狀腺功能低下；藥物引起甲狀腺毒症

並列摘要

Amiodarone is one of the common use anti-arrhythmia agents around the world. Unfortunately, amiodarone has numerous side effects, including the thyroid dysfunction. Finding out the risk factors associated amiodarone induced thyroid adverse events will be really useful for health professionals to make drug selection and monitoring plan. We conducted a retrospective observational nested case–control study to evaluate patient’s clinical factors associated amiodarone induced thyroid adverse effects. Data were retrospective obtained from medical records in Wan Fang hospital. Potential risk factors associated with amiodarone induced thyroid adverse effects were evaluated by multivariate model in this study. The protocol of this study was approved by TMU-Joint Institutional Review Board (No. 201111023). A total of 169 patients (70.55 +/-11.1 yr; 55.87% male) with a mean follow-up of 2.4±1.48 years were studied. Six (3.5%) patients developed amiodarone-induced thyrotoxicosis , 38 (23%) hypothyroidism and one thyroid cancer. The predictors for all amiodarone-associated thyroid adverse effects were dose (mg/kg) and chronic obstructive pulmonary disease (COPD). Predictors for amiodarone– as-soci ated hypothyroidism were chronic kidney disease (CKD) and dose (mg/kg). Gender was not a predictor for amiodarone-associated thyroid adverse effects. The incidence of amiodarone induced thyroid adverse effects was high. The incidence of amiodarone induced hypothyroidism was higher compared to amiodarone-induced thyrotoxicosis. We built a risk assessment score for amiodarone induced thyoid adverse events. There are 4 risk factors in our risk assessment scores, including higher dose (mg/kg), COPD, CKD, smoking. If patients have scores more than 2, the risk of thyroid adverse effect should be carefully monitored during the period of amiodarone therapy.

並列關鍵字

Amiodarone ； Amiodarone induced hypothyroidism ； Amiodarone induced thyrotoxicosis ； Thyroid ； Risk factors ； COPD ； CKD ； Smoking ； Dose

參考文獻

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5. Wann, L.S., et al., 2011 ACCF/AHA/HRS focused update on the management of patients with atrial fibrillation (updating the 2006 guideline): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation, 2011. 123(1): p. 104-23.

7. Connolly, S.J., et al., Dronedarone in high-risk permanent atrial fibrillation. N Engl J Med, 2011. 365(24): p. 2268-76.

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Amiodarone 引起甲狀腺副作用之風險評估

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