Cardoza, Kathryn; Kang, Amy; Smyth, Brendan; Yi, Tae Won; Pollock, Carol; Agarwal, Rajiv; Bakris, George; ... Mahaffey, Kenneth W; + view all Cardoza, Kathryn; Kang, Amy; Smyth, Brendan; Yi, Tae Won; Pollock, Carol; Agarwal, Rajiv; Bakris, George; Charytan, David M; de Zeeuw, Dick; Wheeler, David C; Zhang, Hong; Cannon, Christopher P; Perkovic, Vlado; Arnott, Clare; Levin, Adeera; Mahaffey, Kenneth W; - view fewer (2024) Geographic and racial variability in kidney, cardiovascular and safety outcomes with canagliflozin: A secondary analysis of the CREDENCE randomized trial. Diabetes, Obesity and Metabolism: a journal of pharmacology and therapeutics , 26 (9) pp. 3530-3540. 10.1111/dom.15685.

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Abstract

Aim: To explore the effect of canagliflozin on kidney and cardiovascular events and safety outcomes in individuals with type 2 diabetes and chronic kidney disease across geographic regions and racial groups. Materials and Methods: A stratified Cox proportional hazards model was used to assess efficacy and safety outcomes by geographic region and racial group. The primary composite outcome was a composite of end-stage kidney disease (ESKD), doubling of the serum creatinine (SCr) level, or death from kidney or cardiovascular causes. Secondary outcomes included: (i) cardiovascular death or heart failure (HF) hospitalization; (ii) cardiovascular death, myocardial infarction (MI) or stroke; (iii) HF hospitalization; (iv) doubling of the SCr level, ESKD or kidney death; (v) cardiovascular death; (vi) all-cause death; and (vii) cardiovascular death, MI, stroke, or hospitalization for HF or for unstable angina. Results: The 4401 patients were divided into six geographic region subgroups: North America (n = 1182, 27%), Central and South America (n = 941, 21%), Eastern Europe (n = 947, 21%), Western Europe (n = 421, 10%), Asia (n = 749, 17%) and Other (n = 161, 4%). The analyses included four racial groups: White (n = 2931, 67%), Black or African American (n = 224, 5%), Asian (n = 877, 20%) and Other (n = 369, 8%). Canagliflozin reduced the relative risk of the primary composite outcome in the overall trial by 30% (hazard ratio 0.70, 95% confidence interval 0.59-0.82; P = 0.00001). Across geographic regions and racial groups, canagliflozin consistently reduced the primary composite endpoint without evidence of heterogeneity (interaction P values of 0.39 and 0.91, respectively) or significant safety outcome differences. Conclusions: Canagliflozin reduces the risk of kidney and cardiovascular events similarly across geographic regions and racial groups.

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