Prognostic Impact of Dapagliflozin in Elderly Breast Cancer Survivors with Heart Failure with Preserved Ejection Fraction and Type 2 Diabetes postprint

Abstract: Background　With advances in cancer diagnosis and treatment technologies，as well as the rapid development of anti-cancer drugs，the survival of cancer survivors has significantly improved. Cardiovascular diseases，particularly heart failure，resulting from cancer treatment have become a significant concern. Dapagliflozin，a novel sodium-glucose cotransporter 2（SGLT2）inhibitor，has demonstrated significant clinical benefits in the treatment of type 2 diabetes and heart failure（HF）. However，studies on its prognostic impact in elderly breast cancer survivors with heart failure with preserved ejection fraction（HFpEF）and type 2 diabetes remain scarce. Objective　To investigate the prognostic impact of dapagliflozin in elderly breast cancer survivors with HFpEF and type 2 diabetes. Methods　Ninety-three elderly female breast cancer survivors with HFpEF and type 2 diabetes admitted to the Affiliated Hospital of Qingdao University from January 2018 to August 2023 were enrolled. Based on the medication regimen，patients were divided into the dapagliflozin group（47 patients） and the control group（46 patients）. Baseline data were collected，and patients were followed up for 6 months，with the follow-up period ending in April 2024. The primary endpoint was the occurrence of rehospitalization due to heart failure during the follow-up. Adverse reactions during the follow-up were also recorded. The Kaplan-Meier method was used to plot survival curves，and the Log-rank test was used for comparisons between groups. A multivariate Cox proportional hazards model was employed to analyze the factors influencing rehospitalization events. Results　The average age of the patients was（70.1±3.8）years. There were no statistically significant differences in baseline characteristics between the two groups（P>0.05）. After 6 months of treatment，both the dapagliflozin group and the control group showed decreased levels of fasting plasma glucose（FPG） and glycated hemoglobin（HbA1c），and increased estimated glomerular filtration rate（eGFR）（P<0.05）. At 6 months post-treatment，the dapagliflozin group had lower FPG and HbA1c levels and higher eGFR levels compared to the control group （P<0.05）. Additionally，the left ventricular end-diastolic diameter（LVEDD），interventricular septal thickness（IVST），left ventricular posterior wall thickness（LVPWT），early diastolic mitral valve flow velocity（E）/early diastolic mitral annular peak velocity（e'），left atrial volume index（LAVI），and left ventricular mass index（LVMI）decreased in both groups，while the left ventricular ejection fraction（LVEF）increased compared to pre-treatment levels（P<0.05）. At 6 months post-treatment，the dapagliflozin group had lower LVEDD，IVST，LVPWT，LVMI，LAVI，and E/e'，and higher LVEF compared to the control group（P<0.05）. Levels of high-sensitivity cardiac troponin I（hs-cTnI）and N-terminal pro-B-type natriuretic peptide（NT-proBNP）decreased in both groups after 6 months of treatment（P<0.05）. At 6 months post-treatment，the dapagliflozin group had lower hs-cTnI and NT-proBNP levels compared to the control group（P<0.05）. During the 6-month follow-up，5 patients（10.6%）in the dapagliflozin group and 13 patients（28.3%）in the control group were rehospitalized due to heart failure. Kaplan-Meier survival analysis showed a statistically significant difference in cumulative rehospitalization-free survival rates between the two groups（P=0.032 6）. Multivariate Cox regression analysis results indicated that the use of dapagliflozin（HR=0.325，95%CI=0.116-0.912，P=0.033），angiotensin-converting enzyme inhibitors/angiotensin receptor blockers/angiotensin receptor neprilysin inhibitors（HR=0.562，95%CI=0.236-0.949，P=0.035），and spironolactone（HR=0.836，95%CI=0.710-0.985，P=0.037）were protective factors against rehospitalization events，while increasing age（HR=1.343，95%CI=1.198-1.506，P<0.001），higher BMI（HR=1.305，95%CI=1.111-1.532，P=0.001），and the use of anthracyclines （HR=1.197，95%CI=1.035-1.384，P=0.023）were risk factors for increased rehospitalization events. Conclusion　In elderly breast cancer survivors with HFpEF and type 2 diabetes，dapagliflozin not only effectively controls blood glucose and improves renal function but also significantly improves cardiac function，enhancing long-term prognosis.