盐酸曲美他嗪治疗与肺癌生存：对代谢重编程的影响。

Treatment with trimetazidine dihydrochloride and lung cancer survival: Implications on metabolic re-programming.

机构信息

Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong SAR, China; Division of Experimental Medicine and Immunotherapeutics, Cambridge University Hospitals NHS Foundation Trust / University of Cambridge, UK; Department of Cardiology, Royal Papworth Hospital, Cambridge Biomedical Campus, UK; Institute of Cardiovascular Science and Medicine, The University of Hong Kong, Hong Kong SAR, China; Genetics Research Program for Personalized Medicine in Cardiac Oncology, The University of Hong Kong, Hong Kong SAR, China.

Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong SAR, China.

出版信息

Lung Cancer. 2024 Nov;197:107996. doi: 10.1016/j.lungcan.2024.107996. Epub 2024 Oct 24.

DOI:10.1016/j.lungcan.2024.107996

PMID:39490205

Abstract

BACKGROUND

Metabolic re-wiring with preferential fatty acid oxidation has been observed in lung cancer cells. Whether the use of trimetazidine, an anti-anginal agent that inhibits fatty acid oxidation, alters clinical outcomes in ischemic heart disease (IHD) patients with lung cancers is unknown.

METHODS

We carried out this territory-wide, retrospective cohort study of 279,894 IHD patients prescribed with trimetazidine or long-acting oral nitrates in Hong Kong (population coverage of 7.5 millions, January 1999 - December 2020). A total of 6561 patients with pre-existing or de novo lung cancers were identified. Clinical outcomes of all-cause mortality were longitudinally compared between lung cancer patients who received trimetazidine (n = 547) versus non-users (control, n = 6014).

RESULTS

Over 902.9 ± 1410.6 days, lower incidence of deaths occurred in the trimetazidine group (79.0 %, n = 432/547) compared to controls (90.5 %, n = 5442/6014, P < 0.001). Kaplan-Meier analyses showed that trimetazidine use was associated with significantly higher survival from all-cause mortality in IHD patients (trimetazidine: mean survival = 1840.6 [95 %CI 1596.0-2085.3], versus control: 1056.7 [95 %CI 1011.3-1102.0] days, Log Rank = 69.4, P < 0.001). Cox regression showed that trimetazidine use was significantly associated with reduced risk of all-cause mortality in crude (HR = 0.60 [95 %CI: 0.53 to 0.68], P < 0.001) and multivariable models (HR = 0.65 [95 % CI: 0.57 to 0.74], P < 0.001). Pre-specified analyses amongst patients with pre-existing lung cancers yielded similar findings (HR = 0.49 [95 %CI: 0.35 to 0.67], P < 0.001). Survival benefits related to trimetazidine use was predominantly restricted to non-cardiovascular mortality (P < 0.001).

CONCLUSIONS

Trimetazidine use is associated with higher overall survival in IHD patients with lung cancers, particularly from non-cardiovascular death. These findings need to be confirmed by randomized controlled trials.

摘要

背景

肺癌细胞中观察到代谢重编程和脂肪酸氧化的优先作用。三乙氧嘧啶是一种抑制脂肪酸氧化的抗心绞痛药物，在患有肺癌的缺血性心脏病（IHD）患者中使用该药物是否会改变临床结局尚不清楚。

方法

我们对香港的 279894 名接受三乙氧嘧啶或长效口服硝酸酯类药物治疗的 IHD 患者（人口覆盖 750 万，1999 年 1 月至 2020 年 12 月）进行了这项全港范围的回顾性队列研究。共确定了 6561 例患有预先存在或新发肺癌的患者。在接受三乙氧嘧啶治疗的肺癌患者（n=547）与非使用者（对照组，n=6014）之间，对全因死亡率的临床结局进行了纵向比较。

结果

在 902.9±1410.6 天的时间内，三乙氧嘧啶组的死亡率较低（79.0%，n=432/547），而对照组为 90.5%（n=5442/6014，P<0.001）。Kaplan-Meier 分析显示，三乙氧嘧啶的使用与 IHD 患者全因死亡率的生存显著相关（三乙氧嘧啶：平均生存时间=1840.6[95%CI 1596.0-2085.3]，对照组：1056.7[95%CI 1011.3-1102.0]天，Log Rank=69.4，P<0.001）。Cox 回归显示，三乙氧嘧啶的使用与全因死亡率的风险降低显著相关，在粗模型（HR=0.60[95%CI：0.53 至 0.68]，P<0.001）和多变量模型（HR=0.65[95%CI：0.57 至 0.74]，P<0.001）中均如此。在预先存在肺癌的患者中进行的预设分析得出了类似的结果（HR=0.49[95%CI：0.35 至 0.67]，P<0.001）。与三乙氧嘧啶使用相关的生存获益主要限于非心血管死亡率（P<0.001）。