Effect of empagliflozin on cardiac remodelling in South Asian and non-South Asian individuals: insights from the EMPA-HEART CardioLink-6 randomised clinical trial

William Barbour; Erika Wolff; Pankaj Puar; Makoto Hibino; Ehab Bakbak; Aishwarya Krishnaraj; Raj Verma; Meena Verma; Adrian Quan; Andrew T Yan; Kim A Connelly; Hwee Teoh; C David Mazer; Subodh Verma

doi:10.1186/s12872-023-03549-5

Effect of empagliflozin on cardiac remodelling in South Asian and non-South Asian individuals: insights from the EMPA-HEART CardioLink-6 randomised clinical trial

BMC Cardiovasc Disord. 2023 Nov 15;23(1):557. doi: 10.1186/s12872-023-03549-5.

Authors

William Barbour^#^{1

2}, Erika Wolff^#^{1

3}, Pankaj Puar^#^{1

4

5}, Makoto Hibino⁶, Ehab Bakbak^{1

4}, Aishwarya Krishnaraj^{1

4}, Raj Verma^{1

7}, Meena Verma¹, Adrian Quan¹, Andrew T Yan^{8

9}, Kim A Connelly^{8

9

10}, Hwee Teoh^{1

11}, C David Mazer^{4

10

12

13}, Subodh Verma^{14

15

16}

Affiliations

¹ Division of Cardiac Surgery, St. Michael's Hospital of Unity Health Toronto, 30 Bond Street, Toronto, ON, M5B 1W8, Canada.
² Department of Physiology and Pharmacology, Western University, London, ON, N6A 5C1, Canada.
³ School of Medicine, University College Cork, Cork, T12 K8AF, Ireland.
⁴ Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, M5S 1A8, Canada.
⁵ Faculty of Medicine, University of British Columbia, Vancouver, BC, V6T 1Z3, Canada.
⁶ Division of Cardiothoracic Surgery, Emory University School of Medicine, Atlanta, GA, 30322, USA.
⁷ School of Medicine, Royal College of Surgeons in Ireland, Dublin, D02 YN77, Ireland.
⁸ Division of Cardiology, St. Michael's Hospital of Unity Health Toronto, Toronto, ON, M5B 1W8, Canada.
⁹ Department of Medicine, University of Toronto, Toronto, ON, M5S 1A8, Canada.
¹⁰ Department of Physiology, University of Toronto, Toronto, ON, M5S 1A8, Canada.
¹¹ Division of Endocrinology and Metabolism, St. Michael's Hospital of Unity Health Toronto, 30 Bond Street, Toronto, ON, M5B 1W8, Canada.
¹² Department of Anesthesia, St. Michael's Hospital of Unity Health Toronto, Toronto, ON, M5B 1W8, Canada.
¹³ Department of Anesthesiology and Pain Medicine, University of Toronto, Toronto, ON, M5G 1E2, Canada.
¹⁴ Division of Cardiac Surgery, St. Michael's Hospital of Unity Health Toronto, 30 Bond Street, Toronto, ON, M5B 1W8, Canada. subodh.verma@unityhealth.to.
¹⁵ Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, M5S 1A8, Canada. subodh.verma@unityhealth.to.
¹⁶ Department of Surgery, University of Toronto, Toronto, ON, M5T 1P5, Canada. subodh.verma@unityhealth.to.

^# Contributed equally.

Abstract

Background: This exploratory sub-analysis of the EMPA-HEART CardioLink-6 trial examined whether the previously reported benefit of the sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin on left ventricular (LV) mass (LVM) regression differs between individuals of South Asian and non-South Asian ethnicity.

Methods: EMPA-HEART CardioLink-6 was a double-blind, placebo-controlled clinical trial that randomised 97 individuals with type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD) to either empagliflozin 10 mg daily or placebo for 6 months. LV parameters and function were assessed using cardiac magnetic resonance imaging. The 6-month changes in LVM and LV volumes, all indexed to baseline body surface area, for South Asian participants were compared to those for non-South Asian individuals.

Results: Compared to the non-South Asian group, the South Asian sub-cohort comprised more males, was younger and had a lower median body mass index. The adjusted difference for LVMi change over 6 months was -4.3 g/m² (95% confidence interval [CI], -7.5, -1.0; P = 0.042) for the South Asian group and -2.3 g/m² (95% CI, -6.4, 1.9; P = 0.28) for the non-South Asian group (P_interaction = 0.45). There was no between-group difference for the adjusted differences in baseline body surface area-indexed LV volumes and LV ejection fraction.

Conclusions: There was no meaningful difference in empagliflozin-associated LVM regression between South Asian and non-South Asian individuals living with T2DM and CAD in the EMPA-HEART CardioLink-6 trial.

Trial registration: ClinicalTrials.gov Identifier: NCT02998970 (First posted on 21/12/ 2016).

Keywords: Coronary artery disease; Left ventricular mass regression; SGLT2 inhibition; South Asian ethnicity; Type 2 diabetes mellitus.

Publication types

Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Coronary Artery Disease* / drug therapy
Diabetes Mellitus, Type 2* / diagnosis
Diabetes Mellitus, Type 2* / drug therapy
Double-Blind Method
Humans
Male
Sodium-Glucose Transporter 2 Inhibitors* / adverse effects
Treatment Outcome
Ventricular Remodeling

Substances

empagliflozin
Sodium-Glucose Transporter 2 Inhibitors

Associated data

ClinicalTrials.gov/NCT02998970