Empagliflozin reduces mortality in patients with type 2 diabetes and a history of left ventricular hypertrophy: a sub-analysis of the EMPA-REG OUTCOME trial

Abstract

BACKGROUND: In patients with type 2 diabetes, left ventricular hypertrophy (LVH) is an established predictor of cardiovascular (CV) risk; whether glucose-lowering therapy reduces CV events in this high-risk group remains unknown. In the EMPA-REG OUTCOME trial, empagliflozin reduced the risk of 3-point MACE (composite of CV death, MI, or stroke) (primary outcome) by 14%, CV death by 38% and all-cause mortality by 35% vs placebo in patients with type 2 diabetes and established CV disease. In this post hoc analysis, we investigated the effects of empagliflozin on CV events and mortality in patients with ECG LVH.

METHODS: A total of 7020 patients with type 2 diabetes and established CV disease received study drug. Patients without a baseline ECG, an uninterpretable ECG, or who took study drug prior to baseline ECG were excluded from the analysis.

RESULTS: Of 5973 patients included in this analysis, 140 had ECG LVH at baseline. The incidence rate for CV death (per 1000 patient-years) was 78.9 vs 19.1 in placebo-treated patients with vs without LVH and 32.1 vs 11.6 in empagliflozin-treated patients with vs without LVH. The incidence rates for 3-point MACE and all-cause mortality were also approximately 4 times higher in those with than without LVH. Empagliflozin reduced CV events to a greater extent in patients with LVH at baseline. The hazard ratios (95% CI) for 3-point-MACE were 0.39 (0.19, 0.81) in patients with LVH vs 0.89 (0.76, 1.05) in those without LVH (p-value for interaction = 0.0295). The hazard ratios for CV death were 0.40 (0.16, 1.01) in patients with LVH vs 0.60 (0.47, 0.78) in patients without LVH (p-value for interaction = 0.4034). The hazard ratios for all-cause death were 0.32 (0.13, 0.78) in patients with LVH vs 0.67 (0.55, 0.83) in patients without LVH (p-value for interaction = 0.1126). The absolute risk reductions with empagliflozin vs placebo were greater because both the event rates and the relative risk reductions were higher in patients with vs without LVH.

CONCLUSIONS: In patients with type 2 diabetes and CV disease, LVH is associated with significantly higher rates of CV events and mortality. In the EMPA-REG OUTCOME trial, the magnitude of CV benefit with empagliflozin appeared large in the subgroup with LVH.

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