Cardiometabolic outcomes with dapagliflozin after myocardial infarction by baseline ejection fraction: DAPA-MI

ESC Heart Fail. 2025 Dec;12(6):4184-4193. doi: 10.1002/ehf2.15420. Epub 2025 Sep 16.

Abstract

Aims: In the randomized DAPA-MI clinical trial, 10 mg of dapagliflozin once daily improved cardiometabolic outcomes versus placebo after acute myocardial infarction (MI) in patients without established diabetes or heart failure (HF). We assessed associations between baseline left ventricular ejection fraction (LVEF) and cardiometabolic outcomes in DAPA-MI.

Methods: The primary outcome, assessed using the win ratio method, was the hierarchical composite of death, hospitalization for HF, non-fatal MI, atrial fibrillation/flutter, Type 2 diabetes, New York Heart Association classification at last visit and body weight decrease of ≥5% from baseline to last visit. For the present analysis, patients were categorized using LVEF at randomization (<50% or ≥50%).

Results: Of the DAPA-MI participants with available LVEF data who received ≥1 dose of study drug (n = 3751), 2913 (77.7%) had LVEF <50% and 838 (22.3%) had LVEF ≥50%. The primary hierarchical composite outcome resulted in a win ratio favouring dapagliflozin of 1.38 (95% CI: 1.21, 1.57; P < 0.001) in patients with LVEF <50% and 1.32 (1.00, 1.73; P = 0.048) in patients with LVEF ≥ 50% (P interaction = 0.76). In a sensitivity analysis excluding patients with LVEF <30%, the primary hierarchical composite outcome resulted in a win ratio favouring dapagliflozin of 1.40 (95% CI: 1.22, 1.61; P < 0.001). There were no significant interactions between baseline LVEF and any secondary outcomes.

Conclusions: Regardless of baseline LVEF, dapagliflozin resulted in significant cardiometabolic benefits versus placebo, although there was no impact on the composite of cardiovascular death or hospitalization for HF.

Keywords: dapagliflozin; heart failure; left ventricular ejection fraction; myocardial infarction; sodium–glucose cotransporter‐2 inhibitors.

Publication types

  • Randomized Controlled Trial
  • Multicenter Study

MeSH terms

  • Aged
  • Benzhydryl Compounds* / administration & dosage
  • Benzhydryl Compounds* / therapeutic use
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Glucosides* / administration & dosage
  • Glucosides* / therapeutic use
  • Humans
  • Male
  • Middle Aged
  • Myocardial Infarction* / complications
  • Myocardial Infarction* / drug therapy
  • Myocardial Infarction* / physiopathology
  • Sodium-Glucose Transporter 2 Inhibitors / administration & dosage
  • Sodium-Glucose Transporter 2 Inhibitors / therapeutic use
  • Stroke Volume* / physiology
  • Treatment Outcome
  • Ventricular Function, Left* / physiology

Substances

  • Benzhydryl Compounds
  • dapagliflozin
  • Glucosides
  • Sodium-Glucose Transporter 2 Inhibitors

Grants and funding