Efficacy and Safety of Dapagliflozin in Acute Heart Failure: Rationale and Design of the DICTATE-AHF trial
Dapagliflozin, a sodium-glucose cotransporter-2 inhibitor (SGLT2i) helps to reduce cardiovascular death and ejection fraction. It also decreases the worsening of heart failure in patients with chronic heart failure. There is limited data to support the suggestion that, early incorporation during an acute heart failure (AHF) hospitalization might ease decongestion, improve natriuresis, and facilitate a safe transition to beneficial emergency therapy for both diabetes and heart failure. Cox and colleagues (2020) published a study titled “Efficacy and Safety of Dapagliflozin in Acute Heart Failure: Rationale and Design of the DICTATE-AHF trial” in the American Heart Journal. The summary of the study is given below:
Objectives:
To investigate the efficacy and safety of starting with dapagliflozin within the first 24- 86 hours of hospitalization in patients with AHF as compared to usual hospital care.
Method:
A prospective, multicenter, open-label, randomized trial was conducted by DICTATE-AHF in the United States. 240 patients were enrolled in the study. Patients with type 2 diabetes who were hospitalized with hypervolemic AHF and an estimated glomerular filtration rate of at least 30 ml/min/1.73m2 89 were included in the study. In the ratio of 1:1, patients were randomly assigned with 10mg dapagliflozin once daily or structured usual care for 5 days or till hospital discharge. Both groups received protocolized diuretic and insulin therapies.
The primary endpoint of the study is the diuretic response demonstrated as the cumulative change in weight per cumulative loop diuretic dose in 40mg intravenous furosemide equivalents. Secondary endpoints include 30-day hospital readmission for AHF or diabetic reasons, inpatient worsening AHF, change in NT-pro B-type natriuretic peptide (NT-proBNP), and measures of natriuresis. Safety endpoints include the occurrence of hyper/hypoglycemia, worsening kidney function, ketoacidosis, inpatient mortality, and hypovolemic hypotension.
Findings:
This DICTATE-AHF trial was designed to investigate several unique hypotheses. Inverse relation is observed between weight-based diuretic efficiency and incidence of adverse outcomes, including hospitalization and mortality across a period of 30 to 180 days after multivariate analyses. SGLT2i was reported to possess natriuretic mechanisms that might improve diuretic efficiency and outcomes during and following AHF hospitalization. The study reports that SGLT2i might improve concerns of adverse events caused due to combination nephron blockade. Also, the addition of dapagliflozin to IV loop diuretic therapy is anticipated to provide additional natriuresis while decreasing the adverse events associated with obstructing the distal convoluted tubule with thiazides. No differences were observed in the primary outcomes of diuretic response, dyspnea, length of stay, or change in natriuretic peptides during hospitalization between the dapagliflozin and placebo group. The study highlights the safety profile of dapagliflozin use in ambulatory patients with and without diabetes.
Hence, incorporation of dapagliflozin early during AHF hospitalization among patients with diabetes might facilitate both optimization and decongestion of chronic HF medical therapies. The DICTATE-AHF trial will further evaluate the safety and efficacy of in-hospital initiation of dapagliflozin in patients with diabetes admitted with AHF.
Limitation:
The authors acknowledge that study has lacked a diuretic protocol. Additionally, only 15 patients had diabetes but the study did not describe or standardize how other diabetic therapies were modified or co-prescribed.
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