BACKGROUND: In the EMPA-REG OUTCOME trial in patients with type 2 diabetes and established cardiovascular (CV) disease, empagliflozin added to standard of care reduced CV death vs placebo by 38% (HR 0.62 [95% CI 0.49, 0.77]), all-cause death by 32% (HR 0.68 [95% CI 0.57, 0.82]) and hospitalisation for heart failure (HHF) by 35% (HR 0.65 [95% CI 0.50, 0.85]). We investigated whether residual CV risk at baseline influenced the effect of empagliflozin on these outcomes.
METHODS: We investigated CV death, all-cause death, HHF and the composite of HHF or CV death with empagliflozin vs placebo in subgroups by degree of CV risk at baseline based on the 10-point TIMI Risk Score for Secondary Prevention (TRS 2°P). P-values for treatment-by-subgroup interaction were obtained from tests of homogeneity of treatment group differences among subgroups with no adjustment for multiple testing.
RESULTS: Based on the TRS 2°P risk score, of 7020 patients who received study drug in the EMPA-REG OUTCOME trial, 12%, 40%, 30% and 18% were at low, intermediate, high and highest residual CV risk, respectively, at baseline. In the placebo group, from low to highest predicted risk, the proportion of patients with CV death increased from 2.2% to 11.2% and the proportion of patients with HHF increased from 1.1% to 10.0%. Effects of empagliflozin on CV death, all-cause death, HHF and HHF or CV death were consistent across subgroups by baseline CV risk score.
CONCLUSIONS: The benefits of empagliflozin on key clinical outcomes in the EMPA-REG OUTCOME trial occurred irrespective of residual CV risk at baseline.