Empagliflozin and Cardiovascular Outcomes in Patients With Type 2 Diabetes and Left Ventricular Hypertrophy: A Subanalysis of the EMPA-REG OUTCOME Trial

Molecular and cellular changes in the diabetic heart lead to aberrant myocardial remodeling, characterized by left ventricular hypertrophy (LVH) and eventual diastolic and/or systolic dysfunction (1,2). Although the differential effects of antihypertensive therapy on cardiovascular outcomes in patients with type 2 diabetes and LVH have been studied, those of antihyperglycemic therapy have not (3). In this post hoc analysis of the Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG OUTCOME) trial, we report the effects of empagliflozin on cardiovascular outcomes in subjects with type 2 diabetes, established cardiovascular disease, and electrocardiogram (ECG) evidence of LVH. EMPA-REG OUTCOME (NCT01131676, ClinicalTrials.gov) enrolled patients with type 2 diabetes, inadequate glycemic control, and established cardiovascular disease who had an estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2 at baseline. In total, 7,020 subjects were treated with empagliflozin 10 mg/day, empagliflozin 25 mg/day, or placebo in addition to standard of care (4). In subgroups with/without LVH at baseline (defined on ECG as RV5/V6 + SV1/V2 >3.5 mV or RaVL ≥1.3 mV plus ≥1 of the following: left atrial abnormality, left axis deviation, and ST- and/or T-wave changes consistent with LVH), we assessed the risks of cardiovascular death, all-cause mortality, and 3-point major adverse cardiovascular events (MACE) with pooled empagliflozin doses versus placebo. We excluded 134 participants without a baseline ECG, 7 who had a baseline ECG that was uninterpretable or did not have QT interval data, and 906 who took the study drug prior to ECG. Therefore, 5,973 participants had a usable baseline ECG (manually analyzed; 2,008 in the placebo group and 3,965 in the empagliflozin groups), of whom 140 had LVH (45 in the placebo group and 95 in the empagliflozin groups). We used a Cox proportional hazards model with factors for age, sex, region, treatment, …