Cheng Yuen-Ting, Sin Chun-Fung, Ma Edmond S K, Lam Stephen T S, Au Yeung Shiu-Lun, Cheung Bernard M Y, Tse Hung-Fat, Yiu Kai-Hang, Chan Yap-Hang
Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong SAR, China.
Department of Pathology, School of Clinical Medicine, The University of Hong Kong, Hong Kong SAR, China.
Commun Med (Lond). 2025 Mar 25;5(1):89. doi: 10.1038/s43856-025-00805-x.
Metabolic reprogramming of energy processes is a cellular hallmark of various cancers. Whether trimetazidine, an anti-ischemic agent that preferentially potentiates cellular glucose oxidation, alters the long-term risk of malignancies is unknown.
In this multi-center, retrospective cohort study, we studied the effect of trimetazidine on new-onset malignancies in 200,563 ischemic heart disease patients (mean age 70.8 years, 46.6% female) using the Hong Kong Clinical Data Analysis and Reporting System (CDARS), comparing trimetazidine users (n = 16,873) to nitrate users (n = 183,690, as control) over at least 30 days. The primary endpoint was defined as the estimated effect of trimetazidine on the overall new-onset occurrence of any malignancies a priori specified, diagnosed 90 days or more after the cohort entry.
Over a mean follow-up duration of 8.36 (6.42) years, the incidence rate of new-onset malignancies amongst trimetazidine users is significantly lower compared to the non-users (8.76 vs 12.3 per 1000-person years, trimetazidine to control incidence ratio, 0.71). Trimetazidine use is associated with improved event-free survival from new-onset malignancies (Mean survival: 231 [0.53] versus 225 [0.21] months, Chi-square = 161, P < 0.001). Multivariable Cox regression demonstrates an independently lower risk of new-onset malignancies associated with trimetazidine use, with (adjusted HRs, 0.71, 95% CI, 0.66-0.77, P < 0.001) and without (adjusted HRs, 0.71, 95% CI, 0.68-0.75, P < 0.001) propensity score matching. Subgroup analyses of new-onset malignancies including lung, colorectal, hepatobiliary & pancreatic, breast, stomach & oesophageal, renal & genito-urinary, prostate, and hematological malignancies, show similar risk reductions.
Modulation of metabolic reprogramming may represent a new therapeutic target for cancer prevention.
能量代谢重编程是多种癌症的细胞特征。曲美他嗪是一种优先增强细胞葡萄糖氧化的抗缺血药物，它是否会改变恶性肿瘤的长期风险尚不清楚。
在这项多中心回顾性队列研究中，我们使用香港临床数据分析与报告系统（CDARS），研究了曲美他嗪对200563例缺血性心脏病患者（平均年龄70.8岁，46.6%为女性）新发恶性肿瘤的影响，将至少使用曲美他嗪30天的患者（n = 16873）与使用硝酸盐的患者（n = 183690，作为对照）进行比较。主要终点定义为曲美他嗪对队列入组后90天或更长时间诊断出的任何预先指定的新发恶性肿瘤总体发生率的估计影响。
在平均8.36（6.42）年的随访期内，曲美他嗪使用者中新发恶性肿瘤的发病率显著低于未使用者（每1000人年8.76例 vs 12.3例，曲美他嗪与对照的发病率比为0.71）。使用曲美他嗪与新发恶性肿瘤的无事件生存期改善相关（平均生存期：231[0.53]个月 vs 225[0.21]个月，卡方 = 161，P < 0.001）。多变量Cox回归显示，无论是否进行倾向得分匹配，使用曲美他嗪均与新发恶性肿瘤的风险独立降低相关（调整后风险比，0.71，95%置信区间，0.66 - 0.77，P < 0.001；调整后风险比，0.71，95%置信区间，0.68 - 0.75，P < 0.001）。对新发恶性肿瘤的亚组分析，包括肺癌、结直肠癌、肝胆胰癌、乳腺癌、胃癌和食管癌、肾和泌尿生殖系统癌、前列腺癌和血液系统恶性肿瘤，显示出类似的风险降低。
调节代谢重编程可能代表癌症预防的一个新的治疗靶点。
