The use of sodium-glucose cotransporter type 2 inhibitors for the purpose of treating the chronic cardiac failure in oncology patients receiving cardiotoxic chemotherapy: preliminary results

BACKGROUND: Chronic cardiac failure belongs to the most threatening and delayed manifestations of cardiotoxicity in oncology patients receiving the treatment with antitumor medicines. As of today, only two groups of drugs were proven to have significant cardioprotective effects in these categories of patients: angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and beta-adrenergic blockers. Recently, the first data were published on the successful use of sodium-glucose cotransporter type 2 inhibitors in patients with chronic cardiac failure, receiving anthracycline therapy.

AIM: optimization of cardioprotective therapy in the treatment of chronic cardiac failure in oncology patients receiving cardiotoxic chemotherapy.

METHODS: A prospective observational open-label research was carried out with an enrollment of 116 oncology patients with verified chronic cardiac failure, which were receiving cardiotoxic chemotherapy, of which 60 patients of the control group were receiving double cardioprotective therapy (angiotensin-converting enzyme inhibitors/angiotensin receptor blockers) and the 56 patients of the test group were receiving similar therapy with an addition of Dapagliflozin at a dosage of 10 mg once daily in the morning. The controls of the results were conducted in 6 months by means of laboratory and instrumental examinations, as well as by using additional methods of controlling the results.

RESULTS: The groups compared did not differ by the combined primary clinical endpoint (the rate of hospitalizations due to cardio-vascular reasons, the refusal to undergo chemotherapy for the reason of chronic cardiac failure progression and the safety of using the drug products: the presence of urinary tract infections and sepsis), but they differed by the surrogate clinical endpoints that included the dynamic trend of the levels of the groups compared did not differ by the combined primary clinical endpoint (the rate of hospitalizations due to cardio-vascular reasons, the refusal to undergo chemotherapy for the reason of chronic cardiac failure progression and the safety of using the drug products: the presence of urinary tract infections and sepsis), but they differed by the surrogate clinical endpoints that included the dynamic trend of the levels of N-terminal prohormone of brain natriuretic peptide (NT-proBNP) and the global longitudinal strain (GLS) of the left ventricle, determined within the timeframes established for the research — before the initiation of chemotherapy and in 6 months. The patients that have passed all the control tests (n=47), after the end of the 6 months period, underwent a comparison of the levels of troponin Т, left ventricle ejection fraction (LVEF), NT-proBNP and GLS. It was found that the dynamic changes of troponin T levels in both groups did not significantly differ (p=0,260), as well as the LVEF indicator (p=0.340), while the NT-proBNP level was significantly decreasing in the test group — by 7.8% comparing to the control group (p=0.006). Comparable data were obtained for the GLS (the decrease in the test group by 6.5% in relative values) comparing to the control group (p=0.008). In 22/47 (46,8%) patients, chronic cardiac failure was diagnosed before the initiation of chemotherapy, in 25/47 (53,2%), chronic cardiac failure was developing during the antitumor medication therapy. In both groups, a total of 17 (16%) fatal outcomes were registered, none of which was caused by the cardiac failure.

CONCLUSION: We suppose that the decrease in the levels of the cardiac failure marker and the less intensive impairment of the left ventricle longitudinal strain with a background of adding sodium-glucose cotransporter type 2 inhibitors to baseline therapy for chronic cardiac failure in oncology patients receiving cardiotoxic chemotherapy, reflects their cardioprotective potential. Thus, the sodium-glucose cotransporter type 2 inhibitor Dapagliflozin slows down the progression of chronic cardiac failure in oncology patients receiving cardiotoxic chemotherapy.