Does empagliflozin modulate the autonomic nervous system among individuals with type 2 diabetes and coronary artery disease? The EMPA-HEART CardioLink-6 Holter analysis

Abstract Context We examined if empagliflozin was associated with modulation of cardiac autonomic tone among subjects with type 2 diabetes and stable coronary artery disease (CAD) relative to placebo. Methods Using ambulatory 24-hour Holter electrocardiographic data prospectively collected from a randomized trial, we compared changes in heart rate variability (HRV) parameters between empagliflozin and placebo-assigned subjects over a follow-up period of 6 months. Measured HRV domains included: standard deviation (SD) of NN intervals (SDNN), SD of average NN intervals per 5-minutes (SDANN), root mean square of successive RR interval differences (RMSSD), % successive NN intervals differing >50 milliseconds (ms) (pNN50), low frequency (LF), high frequency (HF) and the LF/HF ratio (LF:HF). Differences in HRV parameters between the 2 groups were compared with analysis of covariance (ANCOVA). Statistical measures of significance were reported as adjusted differences between the 2 groups and 95% confidence intervals. Results Sixty-six subjects completed 24-hour Holter monitoring at baseline and 6-months. Over 6 months, the change in HRV was similar between subjects treated with empagliflozin vs. placebo for the following parameters: RMSSD -1.2 ms (-6.0 to -3.6 ms); pNN50 0.5% (-2.6 to 3.6%); VLF -907.8 ms2 (-2388.8 to 573.1 ms2); LF -341 ms2 (-878.7 to 196.7 ms2); HF -33.8 ms2 (-111.1 to 43.5 ms2); LF:HF -0.1 (-0.4 to -0.2). Subjects who received placebo experienced an increase in SDNN 18.6 ms (2.8 to 34.3 ms) and SDANN 20.2 ms (3.2 to 37.3 ms) relative to those treated with empagliflozin. Conclusion Compared to placebo, empagliflozin did not result in changes in autonomic tone among individuals with type 2 diabetes and stable coronary artery disease.