Effects of Empagliflozin on Cardiac Structure in Patients With Type 2 Diabetes - EMPA-HEART CardioLink-6

Contribution To Literature:

The EMPA-HEART CardioLink-6 trial showed that empagliflozin results in salutary effects on LV remodeling at 6 months among patients with DM2 and stable CAD but normal EF and without a clear history of HF.


The goal of the trial was to assess the efficacy of empagliflozin on left ventricular (LV) remodeling among patients with type 2 diabetes mellitus (DM2) with or without prior heart failure (HF).

Study Design

Eligible patients were randomized in a 1:1 fashion to either empagliflozin 10 mg daily (n = 49) or placebo (n = 48). 

  • Total screened: 423
  • Total number of enrollees: 97
  • Duration of follow-up: 6 months
  • Mean patient age: 63 years
  • Percentage female: 7%

Inclusion criteria:

  • ≥40 and ≤80 years of age
  • History of T2DM
  • Hemoglobin A1c ≥6.5% and ≤10 % within 3 months of the screening visit
  • Established coronary artery disease (CAD) (prior coronary revascularization or history of myocardial infarction)
  • Stable (≥2 months) background antihyperglycemic therapy

Exclusion criteria:

  • Using an sodium-glucose cotransporter-2 (SGLT2) inhibitor, glucagon-like peptide-1 receptor agonist (GLP-1 RA), or saxagliptin
  • >4 incidents of moderate hypoglycemia per month or any episode of severe hypoglycemia
  • Estimated glomerular filtration rate <60 ml/min/1.73 m2
  • LV ejection fraction (LVEF) <30%
  • New York Heart Association class IV or recent HHF

Other salient features/characteristics:

  • Duration of DM: 11 years
  • Known chronic HF: 6%
  • Medications: metformin: 94%, insulin 25%, statin 96%, ACEi/ARB 84%, beta-blocker 80%
  • Baseline hemoglobin A1c: 8%
  • Baseline N-terminal pro–B-type natriuretic peptide (NT-proBNP): 175 pg/ml
  • Baseline systolic blood pressure (BP): 135 mm Hg

Principal Findings:

The primary outcome of change in LV mass index on cardiac magnetic resonance (CMR) from baseline to 6 months, for empagliflozin vs. placebo, was  -2.6 vs. -0.01 g/m2, p = 0.01. The greatest improvement among patients with LV mass index was >60 g/m2 (p for interaction = 0.007).

Secondary outcomes, for empagliflozin vs. placebo:

  • Change in systolic BP: -7.9 vs. -0.7 mm Hg, p = 0.003
  • Change in diastolic BP: -3.1 vs. 0.8 mm Hg, p = 0.02
  • Change in hematocrit: 2.4 vs. 0.4%, p = 0.006
  • Change in LV end-systolic volume index : -1.0 vs. 0.04 ml/m2, p = 0.36
  • Change in LVEF: 0.72% vs. -1.0%, p = 0.08


The results of this trial indicate that empagliflozin results in salutary effects on LV remodeling at 6 months among patients with DM2 and stable CAD but normal EF and without a clear history of HF (only 6% had known HF in this trial). This effect was most prominent among those with LV mass index >60 g/m2 at baseline. Salutary effects were also noted for systolic BP and hematocrit, but not in NT-proBNP or troponin levels. This is an interesting mechanistic study that seeks to take a deeper dive into the cardiovascular benefits, particularly HF benefits, noted with empagliflozin in the EMPA-REG OUTCOME trial, and more recently in the DAPA-HF trial.


Verma S, Mazer CD, Yan AT, et al., on behalf of the EMPA-HEART CardioLink-6 Investigators. Effect of Empagliflozin on Left Ventricular Mass in Patients With Type 2 Diabetes and Coronary Artery Disease: The EMPA-HEART CardioLink-6 Randomized Clinical Trial. Circulation 2019;140:1693-1702.

Presented by Dr. Subodh Verma at the American Heart Association Annual Scientific Sessions (AHA 2018), Chicago, IL, November 11, 2018.

Clinical Topics: Anticoagulation Management, Heart Failure and Cardiomyopathies, Atherosclerotic Disease (CAD/PAD), Acute Heart Failure, Heart Failure and Cardiac Biomarkers

Keywords: AHA Annual Scientific Sessions, AHA18, Blood Pressure, Coronary Artery Disease, Diabetes Mellitus, Type 2, Glycated Hemoglobin A, Heart Failure, Hematocrit, Hypoglycemic Agents, Metformin, Natriuretic Peptide, Brain, Peptide Fragments, Troponin T, Ventricular Remodeling

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