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

Published on Jan 23, 2019in Diabetes Care16.019
· DOI :10.2337/DC18-1959
Subodh Verma95
Estimated H-index: 95
(U of T: University of Toronto),
C. David Mazer42
Estimated H-index: 42
(U of T: University of Toronto)
+ 9 AuthorsDavid Fitchett39
Estimated H-index: 39
(St. Michael's Hospital)
Sources
Abstract
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, …
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#2John J.V. McMurray (BHF: British Heart Foundation)H-Index: 197
Last. David Z. I. Cherney (TGH: Toronto General Hospital)H-Index: 7
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Clinical trials often yield surprising results, and in the contemporary era, undoubtedly, the Empagliflozin Removal of Excess of Glucose Outcome (EMPA-REG OUTCOME) trial stands out as one such example.1,2 No one could have predicted that a sodium-dependent glucose cotransporter 2 (SGLT2) inhibitor, which works to promote urinary glucose excretion as a treatment approach to hyperglycemia, would cut all-cause mortality by about one-third in patients with type 2 diabetes. Just as surprising were th...
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BACKGROUND The effects of empagliflozin, an inhibitor of sodium–glucose cotransporter 2, in addition to standard care, on cardiovascular morbidity and mortality in patients with type 2 diabetes at high cardiovascular risk are not known. METHODS We randomly assigned patients to receive 10 mg or 25 mg of empagliflozin or placebo once daily. The primary composite outcome was death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, as analyzed in the pooled empagliflozin...
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