Cerebrovascular, Cognitive and Cardiac Benefits of SGLT2 Inhibitors Therapy in Patients with Atrial Fibrillation and Type 2 Diabetes Mellitus: Results from a Global Federated Health Network Analysis

Riccardo Proietti; José Miguel Rivera-Caravaca; Raquel López-Gálvez; Stephanie L Harrison; Francisco Marín; Paula Underhill; Eduard Shantsila; Garry McDowell; Manlio Vinciguerra; Rhys Davies; Clarissa Giebel; Deirdre A Lane; Gregory Y H Lip

doi:10.3390/jcm12082814

Cerebrovascular, Cognitive and Cardiac Benefits of SGLT2 Inhibitors Therapy in Patients with Atrial Fibrillation and Type 2 Diabetes Mellitus: Results from a Global Federated Health Network Analysis

J Clin Med. 2023 Apr 11;12(8):2814. doi: 10.3390/jcm12082814.

Authors

Riccardo Proietti^{1

2}, José Miguel Rivera-Caravaca^{1

3

4}, Raquel López-Gálvez³, Stephanie L Harrison^{1

2}, Francisco Marín³, Paula Underhill⁵, Eduard Shantsila^{1

6}, Garry McDowell¹, Manlio Vinciguerra¹, Rhys Davies⁷, Clarissa Giebel^{6

8}, Deirdre A Lane^{1

2}, Gregory Y H Lip^{1

2}

Affiliations

¹ Liverpool Centre for Cardiovascular Science at University of Liverpool, Liverpool John Moores University and Liverpool Heart & Chest Hospital, Liverpool L8 7TX, UK.
² Department of Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool L8 7TX, UK.
³ Department of Cardiology, Hospital Clínico Universitario Virgen de la Arrixaca, University of Murcia, Instituto Murciano de Investigación Biosanitaria (IMIB-Arrixaca), CIBERCV, 30120 Murcia, Spain.
⁴ School of Nursing, University of Murcia, 30120 Murcia, Spain.
⁵ TriNetX LLC, London EC3V 4AB, UK.
⁶ Department of Primary Care and Mental Health, University of Liverpool, Liverpool L8 7TX, UK.
⁷ The Walton Centre NHS Foundation Trust, Lower Lane, Liverpool L9 7LJ, UK.
⁸ NIHR Applied Research Collaboration North West Coast, Liverpool L8 7TX, UK.

Abstract

Background: Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are effective anti-diabetic drugs improving cardiovascular outcomes in type 2 diabetes mellitus (T2DM) patients. This study investigated cardiovascular, cerebrovascular and cognitive outcomes of SGLT2i therapy in patients with atrial fibrillation (AF) and T2DM.

Methods: Observational study using TriNetX, a global health research network of anonymised electronic medical records from real-world patients between January 2018 and December 2019. The network includes healthcare organisations globally but predominately in the United States. AF patients (ICD-10-CM code: I48) with T2DM were divided according to SGLT2i use or not, and balanced using propensity score matching (PSM). Patients were followed-up for 3-years. The primary endpoints were ischaemic stroke/transient ischemic attack (TIA), intracranial haemorrhage (ICH), and incident dementia. Secondary endpoints were incident heart failure and mortality.

Results: We identified 89,356 AF patients with T2DM of which 5061 (5.7%) were taking a SGLT2i. After PSM, 5049 patients (mean age 66.7 ± 10.6 years; 28.9% female) were included in each group. At 3-years follow-up, the risk of ischaemic stroke/TIA was higher in patients not receiving SGLT2i (HR 1.12, 95% CI 1.01-1.24) and for ICH (HR 1.57, 95% CI 1.25-1.99) and incident dementia (HR 1.66, 95% CI 1.30-2.12). Incident heart failure (HR 1.50, 95% CI 1.34-1.68) and mortality (HR 1.77, 95% CI 1.58-1.99) risks were increased in AF patients not receiving SGLT2i.

Conclusions: In our large 'real world' analysis of patients with concomitant AF and T2DM, SGLT2i reduced the risk of cerebrovascular events, incident dementia, heart failure and death.

Keywords: SGLT2; atrial fibrillation; dementia; stroke.

Grants and funding

This is independent research funded by the National Institute for Health Research Applied Research Collaboration North West Coast (ARC NWC). The views expressed in this publication are those of the author(s) and not necessarily those of the National Institute for Health Research or the Department of Health and Social Care.