Zhou, Zien, Jardine, Meg J., Li, Qiang, Neuen, Brendon L., Cannon, Christopher P., De Zeeuw, Dick, Edwards, Robert, Levin, Adeera, Mahaffey, Kenneth W., Perkovic, Vlado, Neal, Bruce, Lindley, Richard I., Investigators including, CREDENCE Trial and Bellary, Srikanth (2021). Effect of SGLT2 inhibitors on stroke and atrial fibrillation in diabetic kidney disease: Results from the CREDENCE trial and meta-analysis. Stroke, 52 (5),
Abstract
BACKGROUND AND PURPOSE: Chronic kidney disease with reduced estimated glomerular filtration rate or elevated albuminuria increases risk for ischemic and hemorrhagic stroke. This study assessed the effects of sodium glucose cotransporter 2 inhibitors (SGLT2i) on stroke and atrial fibrillation/flutter (AF/AFL) from CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) and a meta-Analysis of large cardiovascular outcome trials (CVOTs) of SGLT2i in type 2 diabetes mellitus. METHODS: CREDENCE randomized 4401 participants with type 2 diabetes mellitus and chronic kidney disease to canagliflozin or placebo. Post hoc, we estimated effects on fatal or nonfatal stroke, stroke subtypes, and intermediate markers of stroke risk including AF/AFL. Stroke and AF/AFL data from 3 other completed large CVOTs and CREDENCE were pooled using random-effects meta-Analysis. RESULTS: In CREDENCE, 142 participants experienced a stroke during follow-up (10.9/1000 patient-years with canagliflozin, 14.2/1000 patient-years with placebo; hazard ratio [HR], 0.77 [95% CI, 0.55-1.08]). Effects by stroke subtypes were: ischemic (HR, 0.88 [95% CI, 0.61-1.28]; n=111), hemorrhagic (HR, 0.50 [95% CI, 0.19-1.32]; n=18), and undetermined (HR, 0.54 [95% CI, 0.20-1.46]; n=17). There was no clear effect on AF/AFL (HR, 0.76 [95% CI, 0.53-1.10]; n=115). The overall effects in the 4 CVOTs combined were: Total stroke (HRpooled, 0.96 [95% CI, 0.82-1.12]), ischemic stroke (HRpooled, 1.01 [95% CI, 0.89-1.14]), hemorrhagic stroke (HRpooled, 0.50 [95% CI, 0.30-0.83]), undetermined stroke (HRpooled, 0.86 [95% CI, 0.49-1.51]), and AF/AFL (HRpooled, 0.81 [95% CI, 0.71-0.93]). There was evidence that SGLT2i effects on total stroke varied by baseline estimated glomerular filtration rate (P=0.01), with protection in the lowest estimated glomerular filtration rate (45 mL/min/1.73 m2]) subgroup (HRpooled, 0.50 [95% CI, 0.31-0.79]). CONCLUSIONS: Although we found no clear effect of SGLT2i on total stroke in CREDENCE or across trials combined, there was some evidence of benefit in preventing hemorrhagic stroke and AF/AFL, as well as total stroke for those with lowest estimated glomerular filtration rate. Future research should focus on confirming these data and exploring potential mechanisms.
Publication DOI: | https://doi.org/10.1161/STROKEAHA.120.031623 |
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Divisions: | College of Health & Life Sciences > School of Biosciences College of Health & Life Sciences Aston University (General) |
Additional Information: | Copyright © 2021 The Authors. Stroke is published on behalf of the American Heart Association, Inc., by Wolters Kluwer Health, Inc. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial-NoDerivs License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited, the use is noncommercial, and no modifications or adaptations are made. |
Uncontrolled Keywords: | atrial fibrillation,canagliflozin,glomerular filtration rate,hemorrhagic stroke,ischemic stroke,Clinical Neurology,Cardiology and Cardiovascular Medicine,Advanced and Specialised Nursing |
Publication ISSN: | 1524-4628 |
Last Modified: | 28 Mar 2025 08:11 |
Date Deposited: | 17 Jan 2025 10:44 |
Full Text Link: | |
Related URLs: |
http://www.scop ... tnerID=8YFLogxK
(Scopus URL) https://www.aha ... EAHA.120.031623 (Publisher URL) |
PURE Output Type: | Article |
Published Date: | 2021-05 |
Published Online Date: | 2021-04-20 |
Accepted Date: | 2021-03-05 |
Authors: |
Zhou, Zien
Jardine, Meg J. Li, Qiang Neuen, Brendon L. Cannon, Christopher P. De Zeeuw, Dick Edwards, Robert Levin, Adeera Mahaffey, Kenneth W. Perkovic, Vlado Neal, Bruce Lindley, Richard I. Investigators including, CREDENCE Trial Bellary, Srikanth ( ![]() |
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