Mortality differences in coronary patients with breast cancer treated with trimetazidine dihydrochloride: potential therapeutic implications

Trimetazidine, an anti-angina drug with metabolic regulatory effects, has been observationally associated with reduced malignancy risk. However, whether it has clinical implications for established breast cancer is unknown. We retrospectively studied 2,526 patients with pre-existing or de novo breast cancer and ischemic heart disease (IHD) who received trimetazidine therapy or oral nitrate, identified from the Hong Kong Clinical Data Analysis and Reporting System (CDARS) between January 1, 1999, and December 31, 2020. Subjects were classified as trimetazidine users (n=169) versus non-users (n=2,357). Multivariable Cox regression was used to estimate the hazard ratio (HR) and 95% confidence interval (CI) of all-cause mortality in the pre-existing breast cancer group. After a mean follow-up duration of 4,235± 2,272 days, patients with pre-existing breast cancer who received trimetazidine experienced had a longer overall survival from all-cause mortality than the control group (Mean survival, days [95%CI]; Control, 4,543 [4,163-4,923]; Trimetazidine, 5,405 [2,857-7,953]; Breslow [Generalised Wilcoxon], 5.07, p=.02). Cox regression showed that use of trimetazidine was independently associated with lower all-cause mortality (adjusted HR, 0.48; 95% CI, 0.48-0.98; P = .04). Sensitivity analyses analyzing subjects with pre-existing or de novo breast cancer yielded similar findings (adjusted HR, 0.75; 95% CI, 0.60-0.94; P = .01). The survival benefits were mainly conferred to non-cardiovascular mortality (Breslow [Generalised Wilcoxon], 10.6, p=.001). Trimetazidine use is associated with a lower risk of all-cause mortality among breast cancer patients with IHD. While causality cannot be established at present, further randomized controlled trials are warranted to confirm our findings and further elucidate the underlying mechanisms.