Cardiovascular and renal outcomes with canagliflozin according to baseline kidney function: data from the CANVAS Program

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Title: Cardiovascular and renal outcomes with canagliflozin according to baseline kidney function: data from the CANVAS Program
Authors: Neal, BC
Neuen, BL
Ohkuma, T
Matthews, DR
De Zeeuw, D
Mahaffey, KW
Fulcher, G
Desai, M
Li, Q
Deng, H
Rosenthal, N
Jardine, MJ
Bakris, G
Perkovic, V
Item Type: Journal Article
Abstract: Background: Canagliflozin is approved for glucose lowering in type 2 diabetes and confers cardiovascular and renal benefits. We sought to assess whether it had benefits in people with chronic kidney disease (CKD), including those with an estimated glomerular filtration rate (eGFR) between 30 and 45 mL/min/1.73 m2 in whom the drug is not currently approved for use. Methods: The CANagliflozin cardioVascular Assessment Study Program (CANVAS) randomized 10,142 participants with type 2 diabetes and eGFR greater than 30 mL/min/1.73 m2 to canagliflozin or placebo. The primary outcome was a composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke, with other cardiovascular, renal, and safety outcomes. This secondary analysis describes outcomes in participants with and without CKD, defined as eGFR <60 and ≥60 mL/min/1.73 m2, and according to baseline kidney function (eGFR <45, 45-<60, 60-<90, and ≥90 mL/min/1.73 m2). Results: At baseline, 2039 (20.1%) participants had an eGFR <60 mL/min/1.73 m2, of whom 71.6% had a history of cardiovascular disease. The effect of canagliflozin on the primary outcome was similar in people with CKD (HR 0.70, 95% CI 0.55-0.90) and those with preserved kidney function (HR 0.92, 95% CI 0.79-1.07, P heterogeneity = 0.08). Relative effects on most cardiovascular and renal outcomes were similar across eGFR subgroups, with possible heterogeneity suggested only for the outcome of fatal/nonfatal stroke (P heterogeneity = 0.01), as were results for almost all safety outcomes. Conclusions: The effect of canagliflozin on cardiovascular and renal outcomes was not modified by baseline level of kidney function in people with type 2 diabetes and a history or high risk of cardiovascular disease down to eGFR levels of 30 mL/min/1.73 m2. Reassessing current limitations on the use of canagliflozin in CKD may allow additional individuals to benefit from this therapy.
Issue Date: 9-Oct-2018
Date of Acceptance: 12-Jun-2018
ISSN: 0009-7322
Publisher: American Heart Association
Start Page: 1537
End Page: 1550
Journal / Book Title: Circulation
Volume: 138
Issue: 15
Copyright Statement: © 2018 The Authors. Circulation is published on behalf of the American Heart Association, Inc., by Wolters Kluwer Health, Inc. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial-NoDerivs License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited, the use is noncommercial, and no modifications or adaptations are made.
Keywords: canagliflozin
cardiovascular diseases
diabetes mellitus, type 2
glomerular filtration rate
renal insufficiency, chronic
sodium glucose cotransporter 2
treatment outcome
Cardiovascular System & Hematology
1103 Clinical Sciences
1102 Cardiorespiratory Medicine and Haematology
1117 Public Health and Health Services
Publication Status: Published
Online Publication Date: 2018-07-24
Appears in Collections:Faculty of Medicine
Epidemiology, Public Health and Primary Care

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