Empagliflozin reduces cardiovascular events, mortality and renal events in participants with type 2 diabetes after coronary artery bypass graft surgery: subanalysis of the EMPA-REG OUTCOME® randomised trial

Diabetologia. 2018 Aug;61(8):1712-1723. doi: 10.1007/s00125-018-4644-9. Epub 2018 May 19.


Aims/hypothesis: After coronary artery bypass graft (CABG) surgery in individuals with type 2 diabetes, there remains a considerable residual cardiovascular risk. In the EMPA-REG OUTCOME® trial in participants with type 2 diabetes and established cardiovascular disease, empagliflozin reduced the risk of cardiovascular death by 38%, all-cause mortality by 32%, hospitalisation for heart failure by 35% and incident or worsening nephropathy by 39% vs placebo when given in addition to standard of care. The aim of this post hoc analysis of the EMPA-REG OUTCOME® trial was to determine the effects of the sodium glucose cotransporter 2 inhibitor empagliflozin on cardiovascular events and mortality in participants with type 2 diabetes and a self-reported history of CABG surgery.

Methods: The EMPA-REG OUTCOME® trial was a randomised, double-blind, placebo-controlled trial. Participants with type 2 diabetes and established cardiovascular disease were randomised 1:1:1 to receive placebo, empagliflozin 10 mg or empagliflozin 25 mg, once daily, in addition to standard of care. In subgroups by self-reported history of CABG (yes/no) at baseline, we assessed: cardiovascular death; all-cause mortality; hospitalisation for heart failure; and incident or worsening nephropathy (progression to macroalbuminuria, doubling of serum creatinine, initiation of renal replacement therapy or death due to renal disease). Differences in risk between empagliflozin and placebo were assessed using a Cox proportional hazards model.

Results: At baseline, 25% (1175/4687) of participants who received empagliflozin and 24% (563/2333) of participants who received placebo had a history of CABG surgery. In participants with a history of CABG surgery, HRs (95% CI) with empagliflozin vs placebo were 0.52 (0.32, 0.84) for cardiovascular mortality, 0.57 (0.39, 0.83) for all-cause mortality, 0.50 (0.32, 0.77) for hospitalisation for heart failure and 0.65 (0.50, 0.84) for incident or worsening nephropathy. Results were consistent between participants with and without a history of CABG surgery (p > 0.05 for treatment by subgroup interactions).

Conclusions/interpretation: In participants with type 2 diabetes and a self-reported history of CABG surgery, treatment with empagliflozin was associated with profound reductions in cardiovascular and all-cause mortality, hospitalisation for heart failure, and incident or worsening nephropathy. These data have important implications for the secondary prevention of cardiovascular events after CABG in individuals with type 2 diabetes.

Trial registration: ClinicalTrials.gov NCT01131676.

Keywords: Cardiovascular disease; Coronary artery bypass graft; Coronary revascularisation; Diabetes mellitus; Empagliflozin; Sodium glucose cotransporter 2 inhibition; Type 2 diabetes.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Benzhydryl Compounds / therapeutic use*
  • Cardiovascular Diseases / drug therapy*
  • Coronary Artery Bypass*
  • Creatinine / blood
  • Diabetes Mellitus, Type 2 / therapy
  • Diabetic Nephropathies / complications
  • Diabetic Nephropathies / pathology
  • Double-Blind Method
  • Female
  • Glomerular Filtration Rate
  • Glucosides / therapeutic use*
  • Heart Failure / complications
  • Heart Failure / surgery*
  • Hospitalization
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Kidney Diseases / drug therapy*
  • Male
  • Middle Aged
  • Proportional Hazards Models
  • Risk
  • Treatment Outcome


  • Benzhydryl Compounds
  • Glucosides
  • Hypoglycemic Agents
  • Creatinine
  • empagliflozin

Associated data

  • ClinicalTrials.gov/NCT01131676