Effect of SGLT2 Inhibitors on Stroke and Atrial Fibrillation in Diabetic Kidney Disease: Results From the CREDENCE Trial and Meta-Analysis.
| dc.contributor.author | Zhou, Zien | |
| dc.contributor.author | Jardine, Meg J | |
| dc.contributor.author | Li, Qiang | |
| dc.contributor.author | Neuen, Brendon L | |
| dc.contributor.author | Cannon, Christopher P | |
| dc.contributor.author | de Zeeuw, Dick | |
| dc.contributor.author | Edwards, Robert | |
| dc.contributor.author | Levin, Adeera | |
| dc.contributor.author | Mahaffey, Kenneth W | |
| dc.contributor.author | Perkovic, Vlado | |
| dc.contributor.author | Neal, Bruce | |
| dc.contributor.author | Lindley, Richard I | |
| dc.contributor.author | CREDENCE Trial Investigators* | |
| dc.date.accessioned | 2022-12-01T14:16:42Z | |
| dc.date.available | 2022-12-01T14:16:42Z | |
| dc.date.issued | 2021-05 | |
| dc.date.updated | 2022-12-01T14:16:40Z | |
| dc.description.abstract | Background and purposeChronic 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.MethodsCREDENCE 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.ResultsIn 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]).ConclusionsAlthough 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. | |
| dc.identifier.issn | 0039-2499 | |
| dc.identifier.issn | 1524-4628 | |
| dc.identifier.uri | ||
| dc.language | eng | |
| dc.publisher | Ovid Technologies (Wolters Kluwer Health) | |
| dc.relation.ispartof | Stroke | |
| dc.relation.isversionof | 10.1161/strokeaha.120.031623 | |
| dc.subject | CREDENCE Trial Investigators* | |
| dc.subject | Humans | |
| dc.subject | Diabetic Nephropathies | |
| dc.subject | Atrial Fibrillation | |
| dc.subject | Diabetes Mellitus, Type 2 | |
| dc.subject | Meta-Analysis as Topic | |
| dc.subject | Stroke | |
| dc.subject | Canagliflozin | |
| dc.subject | Sodium-Glucose Transporter 2 Inhibitors | |
| dc.title | Effect of SGLT2 Inhibitors on Stroke and Atrial Fibrillation in Diabetic Kidney Disease: Results From the CREDENCE Trial and Meta-Analysis. | |
| dc.type | Journal article | |
| pubs.begin-page | 1545 | |
| pubs.end-page | 1556 | |
| pubs.issue | 5 | |
| pubs.organisational-group | Duke | |
| pubs.organisational-group | School of Medicine | |
| pubs.organisational-group | Clinical Science Departments | |
| pubs.organisational-group | Medicine | |
| pubs.organisational-group | Medicine, Nephrology | |
| pubs.publication-status | Published | |
| pubs.volume | 52 |
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