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Relative and Absolute Risk Reductions in Cardiovascular and Kidney Outcomes With Canagliflozin Across KDIGO Risk Categories: Findings From the CANVAS Program. American journal of kidney diseases : the official journal of the National Kidney Foundation Neuen, B. L., Ohkuma, T. n., Neal, B. n., Matthews, D. R., de Zeeuw, D. n., Mahaffey, K. W., Fulcher, G. n., Blais, J. n., Li MBiostat, Q. n., Jardine, M. J., Perkovic, V. n., Wheeler, D. C. 2020

Abstract

Canagliflozin reduces the risk of cardiovascular and kidney outcomes in type 2 diabetes. This study aimed to assess the relative and absolute effects of canagliflozin on clinical outcomes across different Kidney Disease: Improving Global Outcomes (KDIGO) risk categories based on estimated glomerular filtration rate (eGFR) and urinary albumin:creatinine ratio (UACR.Post-hoc analysis of the Canagliflozin Cardiovascular Assessment Study (CANVAS) Program.& Participants: The CANVAS Program randomized 10,142 participants with type 2 diabetes at high cardiovascular risk and an eGFR of =30 mL/min/1.73 m2 to canagliflozin or placebo.Canagliflozin or matching placebo.The primary outcome was a composite of nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death, with a set of other cardiovascular and kidney pre-specified outcomes.Of 10,142 participants, 10,031 (98.9%) had available baseline eGFR and UACR data. The proportions of participants in low-, moderate-, high-, and very high-risk categories were 58.6%, 25.8%, 10.6%, and 5.0%, respectively. The relative effect of canagliflozin on the primary outcome (HR 0.86, 95% CI 0.75-0.97) was consistent across KDIGO risk categories (P-trend=0.21), with similar results for other cardiovascular and kidney outcomes. Absolute reductions in the primary outcome were greater within higher KDIGO risk categories (P-trend=0.03) with a similar pattern of effect for the composite of cardiovascular death or hospitalization for heart failure (P-trend=0.06) and for chronic eGFR slope (P-trend=0.04).Predominantly a low kidney risk population, relatively few participants in higher KDIGO risk categories, and exclusion of individuals with eGFR <30 mL/min/1.73 m2.While the relative effects of canagliflozin are similar across KDIGO risk categories, absolute risk reductions are likely greater for individuals at higher KDIGO risk. The KDIGO classification system may be able to identify individuals who might derive greater benefits for end-organ protection from treatment with canagliflozin.

View details for DOI 10.1053/j.ajkd.2020.06.018

View details for PubMedID 32971190