Safety of Dapagliflozin in Children with Heart Failure

Abstract

PurposeDapagliflozin recently received FDA-approval for use in adults with heart failure with reduced ejection fraction to reduce the risk of cardiovascular death and hospitalization for heart failure (HF). This is the first report describing safety and use of dapagliflozin in children with HF.MethodsThis is a single-center, observational, retrospective analysis assessing safety of dapagliflozin when added to a background of guideline-directed medical therapy in 9 pediatric patients (age < 21 years) with HF. Only patients with dapagliflozin at steady-state and with follow-up data were included. Univariate comparisons were made using Wilcoxan signed rank test before and after addition of dapagliflozin.ResultsMedian age was 14.2 years (IQR 11.2-17.7; range 9-18). Of the 9 patients, 6 had dilated cardiomyopathy, 2 had single ventricle physiology, and 1 had diastolic HF. NYHA functional class was as follows: 6 were class II, 2 were class III, and 1 was class IV. Median baseline hemoglobin A1c was 5.5% (IQR 5.3-5.75). Most (78%) were started on dapagliflozin during a HF-related hospitalization. Median starting dose of dapagliflozin was 5 mg once daily (IQR 5-10). Mean follow-up was 30.6 days (SD 21.6). Median dose at follow-up was 10 mg once daily (IQR 7.5-10). Urine glucose was negative at baseline and 1+ to 3+ at follow-up confirming the pharmacodynamic effect of dapagliflozin. Total daily dose of loop diuretic was decreased 50% for 3 patients at follow-up. There were no significant differences in weight, blood pressure, heart rate, ejection fraction, B-type natriuretic peptide, estimated glomerular filtration rate or blood chemistries at follow-up. No adverse events such as urinary tract infections, hypoglycemia, fractures, hypovolemia or renal injury were observed. Dapagliflozin was discontinued in 1 patient due to receipt of a heart transplant.ConclusionDapagliflozin appears to be safe in the short term when added to guideline-directed medical therapy for children with heart failure. Dapagliflozin recently received FDA-approval for use in adults with heart failure with reduced ejection fraction to reduce the risk of cardiovascular death and hospitalization for heart failure (HF). This is the first report describing safety and use of dapagliflozin in children with HF. This is a single-center, observational, retrospective analysis assessing safety of dapagliflozin when added to a background of guideline-directed medical therapy in 9 pediatric patients (age < 21 years) with HF. Only patients with dapagliflozin at steady-state and with follow-up data were included. Univariate comparisons were made using Wilcoxan signed rank test before and after addition of dapagliflozin. Median age was 14.2 years (IQR 11.2-17.7; range 9-18). Of the 9 patients, 6 had dilated cardiomyopathy, 2 had single ventricle physiology, and 1 had diastolic HF. NYHA functional class was as follows: 6 were class II, 2 were class III, and 1 was class IV. Median baseline hemoglobin A1c was 5.5% (IQR 5.3-5.75). Most (78%) were started on dapagliflozin during a HF-related hospitalization. Median starting dose of dapagliflozin was 5 mg once daily (IQR 5-10). Mean follow-up was 30.6 days (SD 21.6). Median dose at follow-up was 10 mg once daily (IQR 7.5-10). Urine glucose was negative at baseline and 1+ to 3+ at follow-up confirming the pharmacodynamic effect of dapagliflozin. Total daily dose of loop diuretic was decreased 50% for 3 patients at follow-up. There were no significant differences in weight, blood pressure, heart rate, ejection fraction, B-type natriuretic peptide, estimated glomerular filtration rate or blood chemistries at follow-up. No adverse events such as urinary tract infections, hypoglycemia, fractures, hypovolemia or renal injury were observed. Dapagliflozin was discontinued in 1 patient due to receipt of a heart transplant. Dapagliflozin appears to be safe in the short term when added to guideline-directed medical therapy for children with heart failure.