Mechanistic Study Delves Into Heart Failure Benefits Noted With Empagliflozin EMPA-HEART Cardiolink-6 - EMPA-HEART

Sudarshana Datta, M.D.
By Sudarshana Datta, M.D. on

The EMPA-HEART trial showed that empagliflozin resulted in beneficial effects on left ventricular remodeling at 6 months among patients with type 2 diabetes mellitus and stable coronary artery disease (CAD) but normal ejection fraction and without a clear heart failure history. The findings were presented by Dr. Subodh Verma at the American Heart Association Annual Scientific Sessions (AHA 2018) in Chicago, Illinois.

The investigators aimed 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). A total of 423 eligible patients were randomized in a 1:1 ratio to either empagliflozin 10 mg daily (n = 49) or placebo (n = 48). The study included patients who were ≥40 and ≤80 years of age with a history of type 2 diabetes mellitus, 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) and with a stable (≥2 months) background of antihyperglycemic therapy. Side by side, patients using a sodium-glucose cotransporter-2 (SGLT2) inhibitor, glucagon-like peptide-1 receptor agonist (GLP-1 RA), or saxagliptin were excluded. The investigators found that 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. Moreover, the greatest improvement among patients with LV mass index was >60 g/m2 (p for interaction = 0.007). A look at the secondary outcomes, for empagliflozin vs. placebo showed that change in systolic BP was -7.9 vs. -0.7 mm Hg (p = 0.003), change in diastolic BP was 2.0 vs. 0.8 mm Hg (p = 0.22), change in haematocrit was 2.4 vs. 0.4% (p = 0.006), change in LV end-systolic volume index was 1.0 vs. 0.04 ml/m2 (p = 0.36), change in LVEF was 2.2% vs. -0.01% (p = 0.07).

“I plan to increase my use of SGLT2 inhibitors in my patients with type 2 diabetes, especially if they have a history of heart failure and especially if they have a history of coronary heart disease. I would encourage you to do the same and I would also recommend that we urge our colleagues in general medicine, in endocrinology, and in nephrology to consider this information as well.”- Dr. Eliott Antman, M.D.

The results of this trial indicated that empagliflozin resulted in favorable 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). The investigators found that the effect was most prominent among those with Left Ventricular mass index >60 g/m2 at baseline. Beneficial effects were also noted for systolic BP and hematocrit, but not in NT-proBNP or troponin levels. Thus, this was an interesting mechanistic study that sought to delve into the cardiovascular benefits, particularly the heart failure benefits, noted with empagliflozin in the EMPA-REG OUTCOME trial. “I plan to increase my use of SGLT2 inhibitors in my patients with type 2 diabetes, especially if they have a history of heart failure and especially if they have a history of coronary heart disease,”  commented discussant Dr. Elliott Antman, Brigham and Women’s Hospital, Boston,  during the session at AHA. “I would encourage you to do the same and I would also recommend that we urge our colleagues in general medicine, in endocrinology, and in nephrology to consider this information as well,” Dr. Antman remarked.

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