Reduction in Left Ventricular Mass With Empagliflozin Not Mediated Through Effect on Diastolic Function

The reduction in left ventricular mass observed in patients with stable coronary artery disease and type 2 diabetes treated with empagliflozin may not result from an effect of this drug on diastolic function, according to results published in a letter to the editor in the Journal of the American Society of Echocardiography.

Sodium-glucose cotransporter 2 inhibitors such as empagliflozin have been shown to reduce heart failure hospitalization and cardiovascular death in clinical trials. In this prespecified substudy of the EMPA-HEART (Effects of Empagliflozin on Cardiac Structure in Patients With Type 2 Diabetes; Clinicaltrials.gov Identifier: NCT02998970) CardioLink-6 Trial, investigators sought to identify the mechanisms underlying the effects of empagliflozin on left ventricular reverse modeling and diastolic function.

In the EMPA-HEART trial, patients with type 2 diabetes and stable coronary artery disease were randomly assigned to receive empagliflozin (10 mg once daily; n=49) or placebo (n=48). Transthoracic echocardiography was performed at baseline and at 6 months. The study’s primary outcome was the change from baseline to 6 months in the E/e’ ratio.

The changes in average, medial, or lateral E/e’ ratio from baseline to 6 months were comparable in patients treated with empagliflozin vs placebo (average ratio: adjusted difference, -0.23; 95%. CI, -1.29 to 0.82; P =.66).

In addition, empagliflozin vs placebo treatment did not affect the E/e’ ratio in patients with a baseline E/e’ ratio ≥13, with a left ventricular mass index ≥60 g/m², or with a baseline left ventricular ejection fraction >50% vs ≤50%.

Study limitations include a possible underpowering of the identification of changes in diastolic function, and the fact that participants had moderate diastolic dysfunction.

“[T]his prespecified echocardiographic study revealed no significant change in key [left ventricular] diastolic parameters with empagliflozin treatment for 6 months,” the study authors concluded. “These findings suggest that in the EMPA-HEART CardioLink-6 population, changes in loading conditions (ie, preload) did not mediate the observed reduction in [left ventricular] mass.”

Disclosure: Funding for this study was provided by Boehringer Ingelheim. Several authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of disclosures.

Reference

Bami K, Gandhi S, Leong-Poi H, et al. Effects of empagliflozin on left ventricular remodeling in patients with type 2 diabetes and coronary artery disease: Echocardiographic substudy of the EMPA-HEART CardioLink-6 randomized clinical trial [published online March 18, 2020]. J Am Soc Echocardiogr. doi:10.1016/j.echo.2020.02.005

This article originally appeared on The Cardiology Advisor