Cardio-protective effect of trimetazidine in patients with disseminated breast cancer

Abstract

Abstract Funding Acknowledgements Type of funding sources: None. Relevance of the problem. Anthracycline cardiotoxicity is the most unfavorable form due to irreversible complications of cardiovascular system caused by anthracyclines during the chemotherapy (CT) of the breast cancer (BC). Despite the fact that this type of cardiotoxicity has been studied better than others, the problem of preventing such complications remains relevant to this day. In our study, we suggest Trimetadizine (TMZ) as a cardioprotective agent in patients with disseminated breast cancer receiving Doxorubicin chemotherapy. Material and methods The study included 93 patients (aged 41.2±8.3 years) who underwent surgery for breast cancer and several courses of chemotherapy with Doxorubicin (according to the stage of breast cancer). Patients were randomized into 2 groups: the first group (n=47; G1) received TMZ at a dose of 70 mg daily, in the control group (n=46; G2) patients didn't receive TMZ. All patients before the start of the study underwent a complete echocardiographic examination and checked cardiac biomarkers such as troponin and brain natriuretic peptide (BNP). The exclusion criterion was patients with any kind of cardiovascular pathology. The primary endpoint of the study was a reduction in left ventricular ejection fraction (LVEF) deterioration as assessed by series of echocardiographic studies conducted after each course of chemotherapy, and then every 3 months after completion of chemotherapy for 1 year. Secondary outcome measures included echocardiographic (EchoCG) measurements of LV diastolic dysfunction, structural myocardial changes assessed by echocardiography, and control cardiac biomarkers. Results Both groups achieved the same cumulative dose of Doxorubicin. No patient died or discontinued chemotherapy during the study. There were no significant differences between the two groups in terms of baseline clinical findings, echocardiographic parameters, and changes in biomarkers. 3-5 months after the start of CT, standard echocardiography showed unreliable changes in LVEF, shortening fraction, and LV measurements. However, tissue Doppler showed a decrease in myocardial velocity (P = 0.001) in G2, indicating LV diastolic dysfunction. While no such changes were observed in G1. Conclusion Tissue Doppler proved to be more sensitive than standard echocardiography for early diagnosis of cardiac dysfunction, and TMZ appears to have a cardioprotective effect in case of anthracycline cardiotoxicity.