| Contributors: |
Andres Ahuad Guerrero, Rodolfo; Aizenberg, Diego; Pablo Albisu, Juan; Alvarisqueta, Andre; Bartolacci, Ine; Alberto Berli, Mario; Bordonava, Anselmo; Calella, Pedro; Cecilia Cantero, Maria; Rodolfo Cartasegna, Lui; Cercos, Esteban; Cecilia Coloma, Gabriela; Colombo, Hugo; Commendatore, Victor; Cuadrado, Jesu; Alberto Cuneo, Carlo; Maria Cusumano, Ana; Guillermo Douthat, Walter; Dario Dran, Ricardo; Farias, Eduardo; Florencia Fernandez, Maria; Finkelstein, Hernan; Fragale, Guillermo; Osvaldo Fretes, Jose; Horacio Garcia, Nestor; Gastaldi, Anibal; Gelersztein, Elizabeth; Archibaldo Glenny, Jorge; Pablo Gonzalez, Joaquin; Del Carmen Gonzalez Colaso, Patricia; Goycoa, Claudia; Cristian Greloni, Gustavo; Guinsburg, Adrian; Hermida, Sonia; Isaias Juncos, Lui; Isabel Klyver, Maria; Kraft, Florencia; Krynski, Fernando; Virginia Lanchiotti, Paulina; Alfonso Leon De La Fuente, Ricardo; Marchetta, Nora; Mele, Pablo; Nicolai, Silvia; Antonio Novoa, Pablo; Ines Orio, Silvia; Otreras, Fabian; Oviedo, Alejandra; Raffaele, Pablo; Hector Resk, Jorge; Rista, Luca; Rodriguez Papini, Nelson; Sala, Jorgelina; Carlos Santos, Juan; Beatriz Schiavi, Lilia; Sessa, Horacio; Smith Casabella, Toma; Rosa Ulla, Maria; Valdez, Maria; Vallejos, Augusto; Villarino, Adriana; Esther Visco, Virginia; Wassermann, Alfredo; Javier Zaidman, Cesar; Ngai Wah Cheung, Australia; Droste, Carolyn; Fraser, Ian; Johnson, David; Mann Mah, Peak; Nicholls, Kathy; Packham, David; Proietto, Joseph; Roberts, Anthony; Roger, Simon; Tsang, Venessa; Roberto Abrão Raduan, Brazil; Augusto Alves Da Costa, Fernando; Amodeo, Celso; Alberto Andreotti Turatti, Luiz; Bregman, Rachel; Cristina Camelo Sanches, Fernanda; Henrique Canani, Lui; Roberto Chacra, Antônio; Lindolfo Cunha Borges, João; Alberto Cunha Vêncio, Sérgio; Jorge Da Silva Franco, Roberto; D'Avila, Domingo; De Souza Portes, Evandro; De Souza, Pedro; Mônica Deboni, Luciane; Fraige Filho, Fadlo; Geloneze Neto, Bruno; Gomes, Marcu; Keiko Kohara, Suely; Keitel, Elizete; Francisco Kerr Saraiva, Jose; Roberto Kurtz Lisboa, Hugo; Loss De Carvalho Contieri, Fabiana; Milagres, Rosângela; Montenegro Junior, Renan; Moreira De Brito, Claudia |
| 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 ( |