"Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction".

The New England Journal of Medicine. 2019.

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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

Clinical Question

Does dapagliflozin improve outcomes in patients with heart failure and a reduced ejection fraction regardless of the presence or absence of type 2 diabetes?

Bottom Line

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.

Major Points

Guidelines

Design

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

Population

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

Interventions

Patients were randomized to either dapagliflozin or placebo along with standard heart failure therapy.

Outcomes

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)

Secondary Outcomes:
- 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

Criticisms

- Specific inclusion and exclusion criteria may limit generalizability
- Underrepresentation of certain demographics (e.g., black patients, very elderly)
- Low baseline use of sacubitril–valsartan

Funding

Funded by AstraZeneca.

Further Reading

Additional literature relevant to this clinical trial can be found in the Supplementary Appendix provided at NEJM.org.