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Introduction
Ischemic heart disease (IHD) and cancers, as the two leading causes of deaths and morbidities worldwide1, present ever-rising threats to our aging populations. The pressing need to conjunctively combat these two major pandemics cannot be overstated. Accumulating evidence supports some common pathophysiological origins between cardiovascular diseases and cancers, such as systemic inflammation2. Such perspectives in shared etiology may imply the potentials for some cardiovascular drugs to be re-purposed as anti-cancer agents3,4. In this regard, metabolic reprogramming represents one clinical arena that is relatively under-explored.
Metabolic reprogramming is a well-recognized cellular hallmark in various cancers. The Warburg effect described a preferential shift of cellular metabolism in cancer cells from fatty acid oxidation to aerobic glycolysis. This facilitates the derivation of anabolic substrates, and lactic acid formation and creates an acidic environment conducive to cancer cell survival5,6. On the other hand, recapitulation of the fatty acid oxidation pathways has been described in some cancers, particularly in the context of treatment resistance7, 8–9. Here, trimetazidine dihydrochloride, a second-line anti-anginal drug in patients with IHD that specifically inhibits fatty acid oxidation, may impact cancer risk via modulating the metabolic reprogramming pathways10. Firstly, by potentiating glucose oxidation for energy derivation generally in cells, trimetazidine may obliterate the relative survival advantage of cancer cells obtained via the Warburg effect. Secondly, inhibition of fatty acid oxidation by trimetazidine may compromise cellular metabolism in cancer cells that rely predominantly on the beta-oxidation pathways, thus curtailing cancer cell survival. Indeed, these postulations are substantiated by some animal and human experimental studies7,11,12. Studies have shown that trimetazidine induced tumour apoptosis in pancreatic and breast cancer11,12, and may have a protective effect in oxidative lung carcinomas7. Nevertheless, relevant clinical data is absent. We hypothesized that trimetazidine may clinically reduce the risk of new-onset malignancies in persons with IHD. These laid the foundations for this current study.
In this multi-center, territory-wide retrospective cohort study, we find that the use of trimetazidine in patients with IHD is independently associated with reduced risks of malignancy.
Methods
Data source
We conducted this multicenter, retrospective cohort study from the Hong Kong Clinical Data Analysis and Reporting System (CDARS) clinical database. A key...