類風濕性關節炎病人新發生心臟事件的危險因子：methotrexate和腫瘤壞死因子拮抗劑的心臟保護效果

Risk factors for new-onset cardiac events in patients with rheumatoid arthritis: cardioprotective effects of methotrexate and tumor necrosis factor antagonist

目的：為確定在類風濕性關節炎的病人中，心臟事件（冠狀動脈疾病、心臟衰竭、和心律不整）的危險因子，以及比較各種關節炎治療時心臟事件發生率的差異。方法：我們使用台灣國家健康保險研究資料庫資料以及收錄在2002年至2010年間新診斷的類風濕性關節炎病人。病人依治療不同被分為三組。我們比較了1384個以methotrexate治療、2688個以腫瘤壞死因子拮抗劑治療、及4388個以其他傳統疾病修飾藥物治療的病人，新發生心臟事件的發生率。使用Cox比例風險模型計算風險比。結果：冠狀動脈疾病是在所有病人中，最常見的心臟事件。高齡、男性、高血壓、糖尿病、及腎臟疾病是發生心臟事件的獨立因子。經過調整，以 methotrexate或腫瘤壞死因子拮抗劑治療（有／無methotrexate）的病人，比起使用非 methotrexate、非生物製劑治療的病人，發生總心臟事件的風險降低。以 methotrexate或腫瘤壞死因子拮抗劑治療（有／無methotrexate）的病人發生總心臟事件的風險比值分別為0.83（95%信賴區間0.71-0.95，p=0.0096）和0.65（95%信賴區間0.49-0.88, p=0.0051）。尤其是在心臟衰竭。結論：除了傳統的危險因子，methotrexate和腫瘤壞死因子拮抗劑（有／無methotrexate）可降低類風濕性關節炎病人新發生心臟事件的風險。

Objective: To determine the risk factors for cardiac events (coronary artery disease, heart failure, and dysrhythmia) and to compare the cardiac event rates for different anti-arthritic treatments in patients with rheumatoid arthritis (RA). Methods: We used the Taiwan National Health Insurance Research Database and enrolled newly diagnosed RA patients between 2002 and 2010. Patients were stratified based on three mutually exclusive treatment categories. We compared the incidence of new-onset cardiac events between 10,384 methotrexate-treated, 2,688 tumor necrosis factor (TNF) antagonist-treated, and 4,388 other conventional disease modifying anti-rheumatic drug (DMARD)-treated patients. Hazard ratios were calculated using the Cox proportional hazard model. Results: Coronary artery disease was the most common cardiac event among all patients. Old age, male gender, hypertension, diabetes mellitus, and renal disease at baseline were independent predictors for the development of cardiac events. After adjustment, patients treated with methotrexate or TNF antagonists (with/without methotrexate) experienced a reduced risk of composite cardiac events compared to those treated with non-methotrexate, non-biological DMARDs. The hazard ratio for cardiac events in patients treated with methotrexate and TNF antagonists (with/without methotrexate), was 0.83 (95% CI 0.71-0.95, p=0.0096) and 0.65 (95% CI 0.49-0.88, p=0.0051), respectively. The risk reduction was observed especially for heart failure events. Conclusion: In addition to the traditional risk factors, both methotrexate and TNF antagonist treatment (with/without methotrexate) were associated with a reduced risk of new-onset cardiac events in patients with RA.