Treatment with trimetazidine dihydrochloride and lung cancer survival: Implications on metabolic re-programming
Yap-Hang Chan1, Cheng Yuen-Ting2, Chun-Fung Sin3
1Department 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.
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.
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