Skip to content
Evevident
Original paper
2019NEJMCardiology

DAPA-HF

Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction

RCTHeart Failure

On this page

Overview

Dapagliflozin reduced worsening heart failure and cardiovascular death in HFrEF, with or without diabetes.

Clinical takeaway

DAPA-HF showed that the SGLT2 inhibitor dapagliflozin reduces the composite of worsening heart failure and cardiovascular death in patients with HFrEF on top of standard therapy, and crucially the benefit was independent of diabetes status.

Key result

Primary composite: HR 0.74 (95% CI 0.65-0.85), p<0.001.

Practice impact

Helped make SGLT2 inhibitors a foundational pillar of guideline-directed HFrEF therapy.

Evidence

Study design

Randomized, double-blind, placebo-controlled trial

Enrollment

4,744

Follow-up

Median 18.2 months

Geography

Multinational

Clinical question

In patients with heart failure and reduced ejection fraction, does adding dapagliflozin to standard therapy reduce worsening heart failure or cardiovascular death?

Population

  • HFrEF with LVEF <= 40%
  • NYHA class II-IV with elevated NT-proBNP
  • On standard heart-failure therapy
  • Included patients with and without type 2 diabetes

Intervention

Dapagliflozin 10 mg once daily

Comparator

Placebo

Primary outcome

Composite of worsening heart failure (hospitalization or urgent visit) or cardiovascular death

Dapagliflozin reduced worsening heart failure or cardiovascular death versus placebo.

HR / 0.74 / CI 0.65-0.85 / p=<0.001

Key results

  • Primary composite: HR 0.74 (95% CI 0.65-0.85), p<0.001
  • Worsening heart failure events and cardiovascular death each reduced
  • Benefit consistent regardless of diabetes status
  • Improvement in heart-failure-related symptoms

Harms

  • Adverse events related to volume depletion, renal dysfunction, and hypoglycemia did not differ significantly from placebo.
  • SGLT2 inhibitors carry class risks of genital mycotic infection and, rarely, euglycemic diabetic ketoacidosis.

Clinical Use

When to cite

  • When explaining why SGLT2 inhibitors are part of foundational HFrEF therapy
  • When asked whether SGLT2 benefit in HFrEF requires diabetes

Practice impact

  • Made SGLT2 inhibitors a foundational HFrEF therapy
  • Extended SGLT2 inhibitor benefit to non-diabetic patients
  • Incorporated into heart-failure guidelines as class I therapy

Applicability

  • Most useful for symptomatic HFrEF patients already receiving standard background therapy
  • Applies whether or not the patient has type 2 diabetes

Limitations

  • Excluded type 1 diabetes
  • Excluded eGFR < 30 mL/min/1.73m2
  • Excluded symptomatic hypotension or SBP < 95 mmHg

Common misinterpretations

  • Do not frame dapagliflozin only as diabetes therapy in HFrEF.

Related evidence

EMPEROR-Reduced - Same Drug ClassPARADIGM-HF - Same DiseaseDELIVER - Later TrialEMPEROR-Preserved - Later Trial

Citation

McMurray JJV, Solomon SD, Inzucchi SE, et al. Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction. N Engl J Med. 2019;381(21):1995-2008. doi:10.1056/NEJMoa1911303