Effect of SGLT2 Inhibitors on Stroke and Atrial Fibrillation in Diabetic Kidney Disease

Figures

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  Figure 1.. Effects of canagliflozin on stroke in CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation). CANA indicates canagliflozin; eGFR, estimated glomerular filtration rate; HR, hazard ratio; PBO, placebo; and UACR, urinary albumin:creatinine ratio. *P value for interaction across subgroups.

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  Figure 2.. Effects of canagliflozin on the incidence of atrial fibrillation (AF) or atrial flutter (AFL) in CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation). CANA indicates canagliflozin; eGFR, estimated glomerular filtration rate; HR, hazard ratio; PBO, placebo; and UACR, urinary albumin:creatinine ratio. *P value for interaction across subgroups. †Events of AF or AFL were identified from site investigator–reported adverse events.

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  Figure 3.. Meta-analysis of the treatment effects of sodium glucose cotransporter 2 inhibitors (SGLT2i) on stroke and stroke subtypes. CANA indicates canagliflozin; CANVAS, Canagliflozin Cardiovascular Assessment Study; CREDENCE, Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation; DAPA, dapagliflozin; DECLARE-TIMI-58, Dapagliflozin Effect on Cardiovascular Events–Thrombolysis in Myocardial Infarction 58; EMPA, empagliflozin; EMPA-REG OUTCOME, EMPA Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients; HR, hazard ratio; NR, not reported; and PBO, placebo. *Data on ischemic stroke. †Hazard ratio was estimated by risk ratio.

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  Figure 4.. Effects of sodium glucose cotransporter 2 inhibitors (SGLT2i) on stroke according to baseline kidney function. CANA, canagliflozin; CANVAS, Canagliflozin Cardiovascular Assessment Study; CREDENCE, Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation; DAPA, dapagliflozin; DECLARE-TIMI-58, Dapagliflozin Effect on Cardiovascular Events–Thrombolysis in Myocardial Infarction 58; eGFR, estimated glomerular filtration rate; EMPA, empagliflozin; EMPA-REG OUTCOME, Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients; HR, hazard ratio; NR, not reported; and PBO, placebo; *Ischemic stroke only. †Based on screening (rather than baseline) eGFR. ‡The heterogeneity of meta-analysis is I2=36.5% (P=0.19) for all participants, I2=0.0% (P=0.44) for eGFR ≥90 mL/min/1.73 m2 I2=0.0% (P=0.65) for eGFR 60–<90 mL/min/1.73 m2 I2=24.7% (P=0.26) for eGFR 45–<60 mL/min/1.73 m2 and I2=0.0% (P=0.46) for eGFR <45 mL/(min·1.73 m2). §Tested by random-effects meta-regression with the hypothesis of no linear trend across ordered eGFR categories (eGFR ≥90, 60–<90, 45–<60, and <45 mL/min/1.73 m2).