BACKGROUND: In people with type 2 diabetes (T2D) and macrovascular disease, the impact of coexistent microvascular disease on cardiovascular (CV) outcomes is unclear. We evaluated the relationship between baseline (BL) history of microvascular disease and CV outcomes in the EMPA-REG OUTCOME study.
METHODS: Patients with T2D and macrovascular disease (n=7020) were treated with empagliflozin 10 mg, 25 mg or placebo for a median of 3.1 years. We explored the association between investigator-reported history of retinopathy, neuropathy and nephropathy at BL and hospitalization for heart failure (HHF), CV death, CV death or HHF, 3-point major adverse CV event (3P-MACE), incident or worsening nephropathy, and all-cause mortality by Cox regression, adjusting for BL risk factors.
RESULTS: In total, 48.7% of patients had a history of BL microvascular disease (22.0% retinopathy, 31.3% neuropathy, 19.5% nephropathy). Patients with microvascular disease had a longer T2D duration, were more likely to be on insulin, had a lower estimated glomerular filtration rate, and a higher BL prevalence of heart failure and diuretic use. The hazard ratios for the explored outcomes in those with vs. without any microvascular disease in the placebo group were: HHF (1.63 [95% confidence interval 1.06, 2.49]; p=0.025); CV death (1.18 [0.84, 1.66]; p=0.348); CV death or HHF (1.30 [0.97, 1.73]; p=0.075), 3P-MACE (1.16 [0.92, 1.48]; p=0.214); incident or worsening nephropathy (1.72 [1.40, 2.12]; p<0.0001); and all-cause mortality (1.25 [0.93, 1.66]; p=0.135). An increased risk for 3P-MACE, HHF, CV death, HHF or CV death, all-cause mortality and new or worsening nephropathy was seen for patients with all three microvascular complications vs. without any microvascular complications [hazard ratios: 1.7-3.9] in the placebo group. Empagliflozin consistently reduced the risk of all outcomes in those with and without a history of microvascular disease.
CONCLUSIONS: Presence of microvascular disease overlaid on macrovascular disease appears to be associated with a higher risk of HF and cardiorenal outcomes in T2D. Empagliflozin consistently reduced the risk of these outcomes in patients with and without microvascular disease.