乳癌患者使用芳香環酶抑制劑與心血管疾病風險：一項全國性目標試驗模擬研究

Abstract

背景 對於乳癌患者而言心血管疾病已成為重要的議題。雖然芳香環酶抑制劑是在乳癌中常用的藥物，但仍有心血管安全方面疑慮。本研究旨在透過模擬目標試驗評估在台灣女性乳癌患者使用芳香環酶抑制劑相較於泰莫西芬對心血管系統的影響。

方法 本研究利用台灣健保資料庫，針對荷爾蒙受體陽性的停經後乳癌婦女進行目標試驗模擬研究。研究採用複製-審查-加權法 (clone–censor–weight) 來比較芳香環酶抑制劑與泰莫西芬的心血管風險。主要試驗終點為複合性心血管事件(包含冠狀動脈疾病、缺血性中風、心臟衰竭及心房顫動)，次要分析則針對各別心血管事件進行評估。研究利用逆機率加權法結合Cox比例風險模型，估算特定原因的風險比率及其95%信賴區間，以比較兩組藥物之間的疾病風險。

結果 在12,924 名荷爾蒙受體陽性的乳癌患者中，在複製樣本群體裡觀察到芳香環酶抑制劑組有853件複合性心血管事件，泰莫西芬組則有622件。與泰莫西芬相比，使用芳香環酶抑制劑有顯著較高的複合性心血管事件風險 (風險比率為1.24；95%信賴區間為1.13至1.37)。在個別事件分析中則發現心臟衰竭的風險有顯著增加 (風險比率為1.29；95%信賴區間為1.15至1.46)。

結論 針對停經後乳癌女性，接受芳香環酶抑制劑與使用泰莫西芬相比會增加複合性心血管事件及心臟衰竭的風險。未來仍需進一步研究探討心臟衰竭的亞型，並評估芳香環酶抑制劑的長期心血管風險。

Introduction Cardiovascular diseases (CVDs) have emerged as an important concern among breast cancer survivors. While aromatase inhibitors (AIs) are commonly used treatments in breast cancer, concerns have been raised regarding their cardiovascular safety. We aimed to emulate a target trial to evaluate the effect of AIs compared with tamoxifen on the risk of CVDs in women with breast cancer in Taiwan.

Methods We conducted a target trial emulation focused on postmenopausal women with hormone receptor-positive breast cancer using data from the national healthcare databases in Taiwan. The treatment strategies of AIs and tamoxifen were compared using the clone-censor-weight approach. A composite of cardiovascular events, including coronary artery disease, ischemic stroke, heart failure, and atrial fibrillation, was defined as the primary outcome and secondary analyses examined each component individually. Cox proportional hazards models incorporating inverse probability weighting were applied to estimate cause-specific hazard ratios (HRs) and 95% confidence intervals (CIs) for between-group comparisons of CVD risk.

Results Among 12,924 patients with hormone receptor–positive breast cancer, we identified 853 cardiovascular events in individuals treated with AIs and 622 in the tamoxifen group within the cloned population. Compared with tamoxifen, treatment with AIs showed an increased risk of composite cardiovascular events (HR: 1.24; 95% CI: 1.13, 1.37). Among individual outcomes, an increased risk was observed for heart failure (HR 1.29; 95% CI 1.15, 1.46).

Conclusion Among postmenopausal breast cancer patients, treatment with AIs increased the risk of both composite cardiovascular outcomes and heart failure relative to tamoxifen. Further studies are needed to improve characterization of heart failure subtypes and to better understand the long-term cardiovascular safety profile of AIs.