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.

Abstract

BACKGROUND\nSodium-glucose co-transporter 2 (SGLT2) inhibitors lower cardiovascular events in type 2 diabetes (T2DM) but whether they promote direct cardiac effects remains unknown. We sought to determine if empagliflozin causes a decrease in left ventricular (LV) mass in people with T2DM and coronary artery disease (CAD).\n\n\nMETHODS\nBetween November 2016 and April 2018, we recruited 97 individuals ≥40 and ≤80 years old with glycated hemoglobin 6.5 to 10.0%, known CAD and estimated glomerular filtration rate (eGFR) ≥60mL/min/1.73m2. The participants were randomized to empagliflozin (10 mg/day, n=49) or placebo (n=48) for 6 months, in addition to standard of care. The primary outcome was the 6-month change in LV mass indexed (LVMi) to body surface area (BSA) from baseline as measured by cardiac magnetic resonance imaging. Other measures included 6-month changes in LV end-diastolic and -systolic volumes indexed to BSA (LVEDVi and LVESVi), ejection fraction (LVEF), 24-h ambulatory blood pressure, hematocrit and N-terminal pro b-type natriuretic peptide (NT-proBNP).\n\n\nRESULTS\nAmong the 97 participants (90 men [93%], mean [SD] age 62.8 [9.0] years, T2DM duration 11.0 [8.2] years, eGFR 88.4 [16.9] mL/min/1.73m2, LVMi 60.7 [11.9] g/m2) 90 had evaluable imaging at follow-up. Mean LVMi regression over 6 months was 2.6 g/m2 and 0.01 g/m2 for those assigned empagliflozin and placebo, respectively (adjusted difference -3.35 g/m2, 95% CI -5.9 to -0.81g/m2, P=0.01). In the empagliflozin-allocated group, there was significant lowering of overall ambulatory systolic blood pressure (adjusted difference -6.8mmHg, 95% CI -11.2 to -2.3mmHg, P=0.003), diastolic blood pressure (adjusted difference -3.2mmHg, 95% CI -5.8 to -0.6mmHg, P=0.02) and elevation of hematocrit (P=0.0003).\n\n\nCONCLUSIONS\nAmong people with T2DM and CAD, SGLT2 inhibition with empagliflozin was associated with significant reduction in LVMi after 6 months, which may account in part for the beneficial cardiovascular outcomes observed in the EMPA-REG OUTCOME trial.\n\n\nCLINICAL TRIAL REGISTRATION\nURL: https://clinicaltrials.gov Unique Identifier: NCT02998970.