201. Effect of SGLT2 inhibitors on stroke and atrial fibrillation in diabetic kidney disease: Results from the CREDENCE trial and meta-analysis
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Zhou, Z, Jardine, M, Li, Q, Neuen, B, Cannon, C, De Zeeuw, D, Edwards, R, Levin, A, Mahaffey, K, Perkovic, V, Neal, B, Lindley, R, Guerrero, R, Aizenberg, D, Albisu, J, Alvarisqueta, A, Bartolacci, I, Berli, M, Bordonava, A, Calella, P, Cantero, M, Cartasegna, L, Cercos, E, Coloma, G, Colombo, H, Commendatore, V, Cuadrado, J, Cuneo, C, Cusumano, A, Douthat, W, Dran, R, Farias, E, Fernandez, M, Finkelstein, H, Fragale, G, Fretes, J, Garcia, N, Gastaldi, A, Gelersztein, E, Glenny, J, Gonzalez, J, Del Carmen Gonzalez Colaso, P, Goycoa, C, Greloni, G, Guinsburg, A, Hermida, S, Juncos, L, Klyver, M, Kraft, F, Krynski, F, Lanchiotti, P, De La Fuente, R, Marchetta, N, Mele, P, Nicolai, S, Novoa, P, Orio, S, Otreras, F, Oviedo, A, Raffaele, P, Resk, J, Rista, L, Papini, N, Sala, J, Santos, J, Schiavi, L, Sessa, H, Casabella, T, Ulla, M, Valdez, M, Vallejos, A, Villarino, A, Visco, V, Wassermann, A, Zaidman, C, Cheung, N, Droste, C, Fraser, I, Johnson, D, Mah, P, Nicholls, K, Packham, D, 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- 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
- Published
- 2021