Efficacy and Safety of Dapagliflozin in Acute Heart Failure - DICTATE-AHF

Apr 22, 2024
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Author/Summarized by Author:
Amit Saha, MD
Summary Reviewer:
Dharam J. Kumbhani, MD, SM, FACC
Trial Sponsor:
AstraZeneca
Date Presented:
08/28/2023
Date Published:
04/01/2024
Date Updated:
04/22/2024
Original Posted Date:
08/28/2023
References

Contribution To Literature:

Highlighted text has been updated as of April 22, 2024.

The DICTATE-AHF trial showed that in patients with ADHF requiring inpatient IV loop diuretic therapy, there was a trend toward increased diuretic efficiency with the addition of dapagliflozin compared with placebo.

Description:

The goal of the trial was to determine the efficacy and safety of adding the sodium-glucose cotransporter-2 (SGLT2) inhibitor dapagliflozin to intravenous (IV) loop diuretic therapy in patients hospitalized with acute decompensated heart failure (ADHF).

Study Design

  • Randomized
  • Multicenter
  • Open-label

Patients with type 2 diabetes mellitus (DM) who were hospitalized with ADHF regardless of left ventricular ejection fraction (LVEF) were randomized to receive protocolized IV loop diuretic therapy titrated to a goal urine output of 3-5 L/day with the addition of either dapagliflozin 10 mg once daily (n = 119) or placebo (n = 119). The trial protocol was amended in September 2021 to also enroll patients without DM. An open-label design was pursued to permit adjustment of insulin therapy and minimize the risk of hypoglycemia with dapagliflozin.

  • Total number of enrollees: 238
  • Duration of follow-up: 30 days
  • Median patient age: 65
  • Percentage female: 39%

Inclusion criteria:

  • Age ≥18 years
  • ADHF determined by: 1) two signs/symptoms: peripheral edema, ascites, jugular venous pressure >10 mm Hg, orthopnea, paroxysmal nocturnal dyspnea, weight gain ≥5 pounds, pulmonary congestion on imaging; OR 2) pulmonary capillary wedge pressure >19 mm Hg plus one sign/symptom
  • Anticipated or active use of IV loop diuretic
  • Estimated glomerular filtration rate (eGFR) ≥25 mL/min/1.73 m2 (amended September 2021)

Exclusion criteria:

  • Type 1 DM
  • Serum glucose ≤80 mg/dL
  • IV inotropic support
  • History of diabetic ketoacidosis
  • Inability to perform standing weights or accurately record urine output
  • Chronic outpatient therapy with combination loop and thiazide diuretics
  • Chronic dapagliflozin use ≤24 hours prior to randomization

Other salient features/characteristics:

  • Percentage type 2 DM: 71%
  • Percentage LVEF ≤40%: 52%
  • Median eGFR: 53 mL/min/1.73 m2

Principal Findings:

The primary outcome, diuretic efficiency calculated as cumulative weight change divided by cumulative loop diuretic dose and expressed as kg/40 mg IV furosemide-equivalent, for dapagliflozin vs. placebo at 5 days, was: odds ratio 0.65 (95% confidence interval 0.41-1.02), p = 0.06.

  • Median cumulative weight change, dapagliflozin vs. placebo: -4.0 vs. -4.2 kg, p = 1.0
  • Median cumulative loop diuretic dose, dapagliflozin vs. placebo: 560 vs. 800 mg, p = 0.006

Secondary outcomes for dapagliflozin vs. placebo at 30 days:

  • Worsening ADHF during index hospitalization: 3% vs. 3%
  • Readmission for ADHF or DM: 6% vs. 7%

Safety outcomes for dapagliflozin vs. placebo at 30 days:

  • Diabetic ketoacidosis: 0% vs. 0%
  • Symptomatic hypotension: 2% vs. 3%
  • Hypoglycemia: 6% vs. 8%
  • Genitourinary infection: 0% vs. 0.01%
  • Median change in eGFR: -2 vs. -3 mL/min/1.73 m2

Exploratory outcomes for dapagliflozin vs. placebo at 5 days:

  • 24-hour natriuresis: 50 vs. 35 mmol/40 mg IV furosemide (p = 0.025)
  • 24-hour diuresis: 634 vs. 403 mL/40 mg IV furosemide (p = 0.005) 

Interpretation:

The DICTATE-AHF trial demonstrates a trend toward increased diuretic efficiency with the addition of dapagliflozin compared with placebo among patients admitted with ADHF and requiring IV loop diuretics. Although the primary outcome did not achieve significance, the observed increased diuretic efficiency and cumulative diuresis are consistent with that previously associated with empagliflozin in EMPULSE and the smaller, single-center EMPAG-HF trial. No change in 30-day readmissions was noted.

SGTL2 inhibitors are an established component of guideline-directed medical therapy for both HFrEF and HFpEF. Upfront initiation of therapy during ADHF rather than delaying to the outpatient setting appears to be safe but also potentially beneficial. Further large-scale studies may be indicated to confirm the positive exploratory outcomes of greater and more rapid decongestion suggested by the current data.

References:

Cox ZL, Collins SP, Hernandez GA, et al. Efficacy and Safety of Dapagliflozin in Patients With Acute Heart Failure. J Am Coll Cardiol 2024;83:1295-1306.

Editorial Comment: Costanzo MR, Januzzi JL. Early SGLT2 Inhibitors in Acute Heart Failure: Safe Diuretic-Sparing Strategy. J Am Coll Cardiol 2024;83:1307-9.

Presented by Dr. Zachary Cox at the European Society of Cardiology Congress, Amsterdam, Netherlands, August 28, 2023.

Clinical Topics: Dyslipidemia, Lipid Metabolism, Acute Heart Failure, Heart Failure and Cardiomyopathies

Keywords: Acute Heart Failure, Diuretics, ESC Congress, ESC23, Sodium-Glucose Transporter 2


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