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Zhou Z, Jardine MJ, Li Q, et al. Effect of SGLT2 Inhibitors on Stroke and Atrial Fibrillation in Diabetic Kidney Disease: Results From the CREDENCE Trial and Meta-Analysis. Stroke. 2021;52(5):1545-1556doi: 10.1161/STROKEAHA.120.031623.
Zhou, Z., Jardine, M. J., Li, Q., Neuen, B. L., Cannon, C. P., de Zeeuw, D., Edwards, R., Levin, A., Mahaffey, K. W., Perkovic, V., Neal, B., Lindley, R. I. (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), 1545-1556. https://doi.org/10.1161/STROKEAHA.120.031623
Zhou, Zien, et al. "Effect of SGLT2 Inhibitors on Stroke and Atrial Fibrillation in Diabetic Kidney Disease: Results From the CREDENCE Trial and Meta-Analysis." Stroke vol. 52,5 (2021): 1545-1556. doi: https://doi.org/10.1161/STROKEAHA.120.031623
Zhou Z, Jardine MJ, Li Q, Neuen BL, Cannon CP, de Zeeuw D, Edwards R, Levin A, Mahaffey KW, Perkovic V, Neal B, Lindley RI. Effect of SGLT2 Inhibitors on Stroke and Atrial Fibrillation in Diabetic Kidney Disease: Results From the CREDENCE Trial and Meta-Analysis. Stroke. 2021 May;52(5):1545-1556. doi: 10.1161/STROKEAHA.120.031623. Epub 2021 Apr 20. PMID: 33874750; PMCID: PMC8078131.
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Stroke. 2021 May;52(5):1545-1556. doi: 10.1161/STROKEAHA.120.031623. Epub 2021 Apr 20.

Effect of SGLT2 Inhibitors on Stroke and Atrial Fibrillation in Diabetic Kidney Disease: Results From the CREDENCE Trial and Meta-Analysis.

Stroke

Zien Zhou, Meg J Jardine, Qiang Li, Brendon L Neuen, Christopher P Cannon, Dick de Zeeuw, Robert Edwards, Adeera Levin, Kenneth W Mahaffey, Vlado Perkovic, Bruce Neal, Richard I Lindley,

Affiliations

  1. The George Institute for Global Health, UNSW Sydney, Australia (Z.Z., M.J.J., Q.L., B.L.N., V.P., B.N.).
  2. Department of Radiology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, China (Z.Z.).
  3. Concord Repatriation General Hospital, Sydney, Australia (M.J.J.).
  4. Cardiovascular Division, Brigham and Women's Hospital and Baim Institute for Clinical Research, Boston, MA (C.P.C.).
  5. Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, the Netherlands (D.d.Z.).
  6. Janssen Research & Development, LLC, Raritan, NJ (R.E.).
  7. Division of Nephrology, University of British Columbia, Vancouver, BC, Canada (A.L.).
  8. Stanford Center for Clinical Research, Department of Medicine, Stanford University School of Medicine, CA (K.W.M.).
  9. Royal North Shore Hospital, Sydney, Australia (V.P.).
  10. Charles Perkins Centre, University of Sydney, Australia (B.N.).
  11. Imperial College London, London, United Kingdom (B.N.).
  12. Westmead Applied Research Centre, University of Sydney, Sydney, Australia (R.I.L.).
  13. The George Institute for Global Health, Sydney, Australia (R.I.L.).

PMID: 33874750 PMCID: PMC8078131 DOI: 10.1161/STROKEAHA.120.031623

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 (HR

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. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02065791.

Keywords: atrial fibrillation; canagliflozin; glomerular filtration rate; hemorrhagic stroke; ischemic stroke

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