"Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction".
Links to original sources: Wiki Journal Post Full Journal Article
The New England Journal of Medicine. 2019.
PubMed • Full text • PDF
Contents
1 Clinical Question 2 Bottom Line 3 Major Points 4 Guidelines 5 Design 6 Population 6.1 Inclusion Criteria 6.2 Exclusion Criteria 6.3 Baseline Characteristics 7 Interventions 8 Outcomes 8.1 Primary Outcomes 8.2 Secondary Outcomes 8.3 Additional Analyses 9 Criticisms 10 Funding 11 Further Reading
Does dapagliflozin improve outcomes in patients with heart failure and a reduced ejection fraction regardless of the presence or absence of type 2 diabetes?
Among patients with heart failure and reduced ejection fraction, the SGLT2 inhibitor dapagliflozin decreased the risk of worsening heart failure or death from cardiovascular causes and improved symptom scores, irrespective of diabetes status.
Previous trials demonstrated that SGLT2 inhibitors can reduce hospitalization for heart failure in type 2 diabetes patients. This trial, the DAPA-HF study, showed a significant benefit of dapagliflozin in heart failure patients with reduced ejection fraction with or without type 2 diabetes.
As of the knowledge cutoff date, there have been no updates to guidelines based on this study's findings. Heart failure guidelines may be updated in the future to include SGLT2 inhibitors based on the DAPA-HF results.
Phase 3, multicenter, double-blind, placebo-controlled randomized trial N=4744 patients with heart failure and reduced ejection fraction Intervention: Dapagliflozin (10 mg daily) (n=2373) Control: Placebo (n=2371) Median follow-up: 18.2 months
Inclusion Criteria: - ≥18 years old - NYHA class II, III, IV heart failure - Ejection fraction ≤40% - Elevated NT-proBNP levels
Exclusion Criteria: - Recently treated with or intolerant to SGLT2 inhibitors - Type 1 diabetes - Symptoms of hypotension, systolic BP <95 mm Hg - eGFR <30 ml/min/1.73 m²
Baseline Characteristics - Well balanced between groups - 42% with type 2 diabetes at baseline
Patients were randomized to either dapagliflozin or placebo along with standard heart failure therapy.
Primary Outcomes: - Composite of worsening heart failure (hospitalization or urgent visit resulting in IV therapy) or cardiovascular death significantly lower in the dapagliflozin group (16.3% vs. placebo 21.2%; HR, 0.74; P<0.001)
- Improved symptoms based on the Kansas City Cardiomyopathy Questionnaire - No difference in the composite renal outcome between groups
Additional Analyses - Benefit observed early after randomization - Similar benefits in patients without diabetes - Few patients discontinued due to adverse effects
- Specific inclusion and exclusion criteria may limit generalizability - Underrepresentation of certain demographics (e.g., black patients, very elderly) - Low baseline use of sacubitril–valsartan
Funded by AstraZeneca.
Additional literature relevant to this clinical trial can be found in the Supplementary Appendix provided at NEJM.org.