| Contributors: |
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; Proietto, J; Roberts, A; Roger, S; Tsang, V; Raduan, R; Da Costa, F; Amodeo, C; Turatti, L; Bregman, R; Sanches, F; Canani, L; Chacra, A; Borges, J; Vencio, S; Da Silva Franco, R; D'Avila, D; De Souza Portes, E; De Souza, P |
| Description: |
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 ... |