DICTATE-AHF Trial: Early Dapagliflozin in AHF does not meet primary endpoint of diuretic efficiency

By Alberto Castro on

Key Points:

  • The DICTATE-AHF trial explored early initiation of the SGLT2 inhibitor dapagliflozin in acute decompensated heart failure (ADHF) patients.
  • The trial did not show a statistically significant improvement in diuretic efficiency with dapagliflozin compared to structured usual care.
  • However, exploratory analyzes indicated that dapagliflozin improved decongestion and led to earlier hospital discharge without worsening safety outcomes.

The DICTATE-AHF trial investigated the early initiation of dapagliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor, in the context of acute decompensated heart failure (ADHF). The trial’s focus was to determine whether the prompt administration of dapagliflozin within 24 hours of admission could improve diuretic efficiency as compared to structured usual care in patients hospitalized for ADHF. The trial’s design is rooted in addressing a critical dilemma in ADHF management – the balance between achieving complete decongestion and optimizing guideline-directed medical therapy (GDMT). Often, the existing approaches to decongestion, especially using diuretic combinations, do not necessarily align with optimizing GDMT.  The study enrolled adult patients with type 2 diabetes and an estimated glomerular filtration rate (eGFR) of at least 30 mL/min/1.73m2 admitted to hospital with ADHF and current or planned treatment with intravenous (IV) loop diuretics. In September 2021, the protocol was amended to allow enrollment of patients with or without type 2 diabetes and to decrease the eGFR inclusion criterion to 25 mL/min/1.73m2 due to new safety data in these groups. The main exclusion criteria were type 1 diabetes, systolic blood pressure less than 90 mmHg, serum glucose less than 80 mg/dL, use of IV inotropic therapy, and history of diabetic ketoacidosis. The primary outcome was defined as diuretic efficiency expressed as the cumulative change in weight per cumulative loop diuretic dose (IV and oral) from enrollment to day 5 or discharge, if sooner.

The study included total of 240 participants, with an average age of 65 years, 39% of whom were female. When accounting for baseline weight, the odds ratio (OR) for diuretic effectiveness comparing dapagliflozin to structured care was 0.65, with a 95% confidence interval (CI) from 0.41 to 1.01, resulting in a p-value of 0.06. In the analysis without adjustment, the OR stood at 0.64, with a 95% CI ranging from 0.41 to 1.00, and a p-value of 0.05. The secondary outcomes, which included in-hospital exacerbation of heart failure and readmission within 30 days due to heart failure or diabetes-related factors, exhibited no variation between the initiation of dapagliflozin at an early stage and standard care.

One of the key exploratory outcomes showed that patients receiving dapagliflozin experienced enhanced decongestion, leading to a noteworthy reduction in the time to complete intravenous (IV) diuretic therapy and, consequently, an earlier hospital discharge. Dapagliflozin brought about a significant increase in both 24-hour natriuresis (p=0.025) and 24-hour urine output (p=0.005). Additionally, it led to a reduction in both the time required to complete IV diuretic therapy (p=0.006) and the time taken for hospital discharge (p=0.007).

The findings hint at the possibility of enhanced decongestion and earlier hospital discharge, both of which are critical components in the trajectory of ADHF care. Furthermore, the trial’s safety outcomes across various dimensions like inpatient diabetes, cardiovascular events, and renal outcomes, lend confidence to the in-hospital use of dapagliflozin, with potential long-term advantages according to Prof. Zachary Cox, principal investigator of the study.

In conclusion, the DICTATE-AHF trial contributes to the evolving landscape of heart failure management by investigating the potential benefits of early dapagliflozin initiation in ADHF patients. While the primary endpoint was not met, the secondary and exploratory results highlight potential benefits in terms of decongestion and safety. This study serves as a steppingstone for further research and discussion on the role of SGLT2 inhibitors in ADHF care.