The potentially protective effect of dapagliflozin on the development of cardiotoxicity in cancer patients

Abstract

Abstract Introduction The clinical trial "DECLARE-TIMI 58" (Dapagliflozin Effect on Cardiovascular Events-Thrombolysis in Myocardial Infarction 58), demonstrated that dapagliflozin, a Sodium glucose cotransporter 2 inhibitor, reduces the composite end point of cardiovascular death/hospitalization for heart failure in a broad population of patients with type 2 diabetes mellitus.Chemotherapy is known for its potetial adverse effects on myocardium.We hypothesized that early initiation of treatment with dapagliflozin could prevent cardiotoxicity . Purpose We aimed to study if dapagliflozin could exert cardioprotective effects in anthracycline,carfilzomib and trastuzumab-induced cardiotoxicity through the analysis of ejection fraction, global longitudinal strain (GLS) of both left and right ventricle. Methods 32 diabetic patients who were diagnosed with cancer at our medical center were randomized (16 dapagliflozin;16 placebo). The groups were well-matched for baseline characteristics (age, diabetes duration, HbA1c, renal and heart function). Our patients, receiving potentially cardiotoxic treatment: 52% were treated with only trastuzumab, 34% were treated with only anthracycline and 14% with carfilzomib. The primary endpoint was the development of cardiotoxicity after treatment with chemotherapy. Cardiotoxicity was defined as a decrease of LVEF by 5% or more to less than 55% in the presence of symptoms of heart failure or an asymptomatic decrease in LVEF by 10% or more to less than 55%. Results In the first trimester of observation compared to baseline, patients treated with dapagliflozin did not show a deterioration of LV GLS [(GLS = −20,2±3,1% vs −19,8±3,1%, p=0,551] .Similarly in the placebo group [(GLS= −23,02±3,6% vs −22,6±3,5%, p=0,572). No significant changes were found in LVEF after treatment with dapagliflozin (57,9±5,6% vs 57,6±6,1%, p=0,733) or the placebo (60,1±5,6% vs 57,8±6,6%, p=0,166).There was a trend in GLS reduction of left ventricle in 2 patients receiving carfilzomib treatment in the placebo group (p=0.058) Conclusions At the best of our knowledge, our study is the first to investigate the early prophylactic use of dapagiflozin in the development of non-ischemic cardiomyopathy in patients receiving anthracycline or trastuzumab,carflilzomib therapies. During the first trimester of observation there was no benefit by dapagliflozin administration but 2 of our patients in the placebo group demonstrated reduction in GLS of left ventricle.