Empagliflozin reduces mortality in analyses adjusted for control of blood pressure, low density lipoprotein cholesterol and HbA1c over time

 

Aim:

In the EMPA-REG OUTCOME trial, empagliflozin given in addition to standard of care significantly reduced the risk of cardiovascular (CV) (HR 0.62 [95% CI 0.49, 0.77]) and all-cause (0.68 [0.57, 0.82]) mortality vs. placebo in patients with type 2 diabetes and established CV disease. We investigated the effects of control of blood pressure (BP), low density lipoprotein cholesterol (LDL-C) and HbA1c on the treatment difference in mortality.

Methods:

Patients were randomised to empagliflozin 10 mg, empagliflozin 25 mg, or placebo. CV and all-cause mortality were assessed in the pooled empagliflozin group vs. placebo adjusting for control of BP, LDL-C and HbA1c at baseline and during the study as time-dependent covariates. Control was defined as systolic BP < 140 mmHg and diastolic BP < 90 mmHg, LDL-C < 100 mg/dL, and HbA1c < 7.5%.

Results:

Adjusting for control of BP, LDL-C, HbA1c and all these covariates at baseline and during the study, HRs for CV death with empagliflozin vs. placebo were 0.61 (0.49, 0.76), 0.59 (0.47, 0.75), 0.62 (0.49, 0.78) and 0.61 (0.48, 0.76), and for all-cause mortality were 0.67 (0.56, 0.81), 0.66 (0.55, 0.79), 0.67 (0.56, 0.81) and 0.67 (0.56, 0.81), respectively.

Conclusion:

Empagliflozin reduced CV and all-cause mortality to the same extent when analyses were adjusted for control of BP, LDL-C and HbA1c over time, suggesting that the mortality reductions were not driven by controlling or not controlling these CV risk factors during the study.