Results

American College of Cardiology Foundation

11/17/2019 | Press release | Distributed by Public on 11/17/2019 12:58

Dapagliflozin in Patients With Heart Failure and Reduced Ejection Fraction

Contribution To Literature:

The DAPA-HF trial showed that dapagliflozin was superior to placebo at preventing cardiovascular deaths and heart failure events.

Description:

The goal of the trial was to evaluate dapagliflozin (a sodium-glucose cotransporter 2 [SGLT2] inhibitor) compared with placebo among patients with heart failure with reduced ejection fraction (HFrEF).

Study Design

  • Randomized
  • Parallel
  • Placebo

Patients with HFrEF (irrespective of diabetes status) were randomized to dapagliflozin 10 mg daily (n = 2,373) versus placebo (n = 2,371).

  • Total number of enrollees: 4,744
  • Duration of follow-up: 18.2 months
  • Mean patient age: 66 years
  • Percentage female: 24%
  • Percentage with diabetes: 42%

Inclusion criteria:

  • Symptomatic heart failure
  • Left ventricular ejection fraction (LVEF) ≤40%
  • N-terminal pro-B-type natriuretic peptide ≥600 pg/ml (if hospitalized for heart failure within last 12 months ≥400 pg/ml; if atrial fibrillation/flutter ≥900 pg/ml)

Exclusion criteria:

  • Estimated glomerular filtration rate <30 ml/min/1.73 m2
  • Symptomatic hypotension or systolic blood pressure <95 mm Hg
  • Type 1 diabetes mellitus

Principal Findings:

The primary outcome of cardiovascular death, hospitalization for heart failure, or urgent heart failure visit occurred in 16.3% of the dapagliflozin group compared with 21.2% of the placebo group (p < 0.001). The primary outcome was the same in prespecified subgroups, including according to diabetes status.

Secondary outcomes:

  • Cardiovascular death: 9.6% with dapagliflozin vs. 11.5% with placebo
  • Hospitalization for heart failure: 9.7% with dapagliflozin vs. 13.4% with placebo
  • Worsening of renal function: 1.2% with dapagliflozin vs. 1.6% with placebo (p = 0.17)

Results according to age:

Dapagliflozin/placebo hazard ratios (HRs) of the primary outcome for various age groups:

  • 55-64 years: HR 0.71 (95% CI 0.55-0.93)
  • 65-74 years: HR 0.76 (95% CI 0.61-0.95)
  • ≥75 years: HR 0.68 (95% CI 0.53-0.88) (p for interaction = 0.76)

Dapagliflozin and health status:

Dapagliflozin/placebo HRs of the primary outcome according to Kansas City Cardiomyopathy Questionnaire (KCCQ) health status (tertiles):

  • Lowest tertile: HR 0.70 (95% CI 0.57-0.86)
  • Middle tertile: HR 0.77 (95% CI 0.61-0.98)
  • Highest tertile: HR 0.62 (95% CI 0.46-0.83) (p for heterogeneity = 0.52)

Dapagliflozin vs. placebo was associated with a 2.3-point increase in KCCQ overall summary score from baseline to 8 months (p < 0.0001).

Results according to diabetes status:

Dapagliflozin/placebo HRs of the primary outcome according to diabetes:

  • Diabetes: HR 0.75 (95% CI 0.63-0.90)
  • No diabetes: HR 0.73 (95% CI 0.60-0.88) (p for interaction = 0.80)

Interpretation:

Among patients with symptomatic HFrEF, dapagliflozin was beneficial. Dapagliflozin vs. placebo was associated with a reduction in cardiovascular deaths and heart failure events. Dapagliflozin was also associated with improvement in symptoms. Benefit was consistent across the age spectrum, in diabetics/nondiabetics, and across the range of baseline health status. There was no sign of adverse safety events. The baseline use of sacubitril-valsartan was low. Dapagliflozin may signal a new approach in the treatment of patients with HFrEF.

References:

Martinez FA, Serenelli M, Nicolau JC, et al. Efficacy and Safety of Dapagliflozin in Heart Failure With Reduced Ejection Fraction According to Age: Insights From DAPA-HF. Circulation 2019;Nov 17:[Epub ahead of print].

Kosiborod MN, Jhund P, Docherty KF, et al. Effects of Dapagliflozin on Symptoms, Function and Quality of Life in Patients with Heart Failure and Reduced Ejection Fraction: Results from the DAPA-HF Trial. Circulation 2019;Nov 17:[Epub ahead of print].

Presented by Dr. Filipe Martinez at the American Heart Association Annual Scientific Sessions (AHA 2019), Philadelphia, PA, November 17, 2019.

Presented by Dr. John J. McMurray at the American Heart Association Annual Scientific Sessions (AHA 2019), Philadelphia, PA, November 16 and 17, 2019.

McMurray JJ, Solomon SD, Inzucchi SE, et al., on behalf of the DAPA-HF Trial Committees and Investigators. Dapagliflozin in Patients With Heart Failure and Reduced Ejection Fraction. N Engl J Med 2019;Sep 19:[Epub ahead of print].

Editorial: Heart-Failure Therapy - New Drugs but Old Habits? N Engl J Med 2019;Sep 19:[Epub ahead of print].

Presented by Dr. John McMurray at the European Society of Cardiology Congress, Paris, France, September 1, 2019.


Clinical Topics:Anticoagulation Management, Dyslipidemia, Heart Failure and Cardiomyopathies, Lipid Metabolism, Acute Heart Failure, Heart Failure and Cardiac Biomarkers

Keywords:AHA Annual Scientific Sessions, AHA19, ESC Congress, ESC 19, Benzhydryl Compounds, Glomerular Filtration Rate, Glucosides, Heart Failure, Hospitalization, Hypotension, Natriuretic Peptide, Brain, Peptide Fragments, Renal Insufficiency, Sodium-Glucose Transporter 2, Stroke Volume, Diabetes Mellitus


< Back to Listings