Dapagliflozin in Patients With Heart Failure and Reduced Ejection Fraction - DAPA-HF
Contribution To Literature:
The DAPA-HF trial showed that dapagliflozin was superior to placebo at preventing cardiovascular deaths and heart failure events.
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).
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%
- 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)
- Estimated glomerular filtration rate <30 ml/min/1.73 m2
- Symptomatic hypotension or systolic blood pressure <95 mm Hg
- Type 1 diabetes mellitus
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.
- 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 years: HR 0.87 (95% confidence interval [CI] 0.60-1.28)
- 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)
Dapagliflozin and baseline medication use:
- Angiotensin-converting enzyme (ACE) inhibitor/angiotensin-receptor blocker (ARB) target dose <50%: HR 0.78
- ACE inhibitor/ARB target dose ≥50%: HR 0.64 (p for interaction = 0.21)
- Beta-blocker target dose <50%: HR 0.71
- Beta-blocker target dose ≥50%: HR 0.44 (p for interaction = 0.76)
- Mineralocorticoid receptor antagonist (MRA) target dose <50%: HR 0.71
- MRA target dose ≥50%: HR 0.74 (p for interaction = 0.82)
Dapagliflozin and recurrent events (instead of time-to-first events):
- Dapagliflozin vs. placebo, time-to-first event: HR 0.75 (p < 0.0001)
- Dapagliflozin vs. placebo, time-to-recurrent events: HR 0.75 (p < 0.0001)
Among patients with symptomatic HFrEF, dapagliflozin was beneficial. Dapagliflozin vs. placebo was associated with a reduction in cardiovascular deaths and heart failure events. Dapagliflozin vs. placebo was associated with a reduction in recurrent heart failure events and also associated with improvement in symptoms. Benefit was consistent across the age spectrum, in diabetics/nondiabetics, across the range of baseline health status, and baseline medication use. 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.
Presented by Dr. Piotr Ponikowski at the American College of Cardiology Virtual Annual Scientific Session Together With World Congress of Cardiology (ACC 2020/WCC), March 30, 2020.
Docherty KF, Jhund PS, Inzucchi SE, et al. Effects of Dapagliflozin in DAPA-HF According to Background Heart Failure Therapy. Eur Heart J 2020;Mar 28:[Epub ahead of print].
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 2020;141:100-11.
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 2020;141:90-9.
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;381:1995-2008.
Editorial: Heart-Failure Therapy — New Drugs but Old Habits? N Engl J Med 2019;381:2032-42.
Presented by Dr. John McMurray at the European Society of Cardiology Congress, Paris, France, September 1, 2019.
Keywords: acc20, ACC Annual Scientific Session, 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
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