TY - JOUR
T1 - Cardiovascular and renal outcomes with canagliflozin according to baseline kidney function data from the CANVAS program
AU - Neuen, Brendon L.
AU - Ohkuma, Toshiaki
AU - Neal, Bruce
AU - Matthews, David R.
AU - De Zeeuw, Dick
AU - Mahaffey, Kenneth W.
AU - Fulcher, Greg
AU - Desai, Mehul
AU - Li, Qiang
AU - Deng, Hsiaowei
AU - Rosenthal, Norm
AU - Jardine, Meg J.
AU - Bakris, George
AU - Perkovic, Vlado
N1 - Funding Information:
This work was supported by Janssen Research & Development, LLC. The sponsor was involved in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and the decision to submit the manuscript for publication. Medical writing support was provided by Kimberly Dittmar, PhD, of MedErgy, and was funded by Janssen Global Services, LLC. Canagliflozin has been developed by Janssen Research & Development, LLC, in collaboration with Mitsubishi Tanabe Pharma Corp.
Funding Information:
The paper is presented on behalf of the CANVAS Program collaborative group. The authors thank all investigators, study teams, and patients for participating in these studies. The authors thank the following individuals for their contributions to the statistical monitoring/analyses and the protocol development, safety monitoring, and operational implementation over the duration of both studies: Lyndal Hones, Sharon Dunkley, Tao Sun, Gordon Law, George Capua-no, Severine Bompoint, Laurent Billot, Mary Lee, Joan Lind, Roger Simpson, Mary Kavalam, Ed Connell, Jacqueline Yee, Dainius Balis, Frank Vercruysse, Elisa Fabbrini, Richard Oh, Nicole Meyers, Wayne Shaw, and Gary Meininger. B.L.N., T.O., H.D., and Q.L. contributed to the analysis and interpretation of data. B.N., D.R.M., D.d.Z., K.W.M., G.F., M.D., N.R., M.J.J., G.B., and V.P. contributed to the design and conduct of the study and the interpretation of the data. B.L.N. and V.P. wrote the first draft of the manuscript, and all authors contributed to subsequent drafts and approved the final version for submission. V.P. and M.D. are the guarantors of this work and, as such, had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. This work was supported by Janssen Research & Development, LLC. The sponsor was involved in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and the decision to submit the manuscript for publication. Medical writing support was provided by Kimberly Dittmar, PhD, of MedErgy, and was funded by Janssen Global Services, LLC. Canagliflozin has been developed by Janssen Research & Development, LLC, in collaboration with Mitsubishi Tanabe Pharma Corp.
Funding Information:
Dr Neuen is supported by the John Chalmers PhD Scholarship from The George Institute for Global Health and a University Postgraduate Award from University of New South Wales Sydney. Dr Ohkuma is supported by the John Chalmers Clinical Research Fellowship of the George Institute. Q. Li reports being full-time employees of The George Institute for Global Health. Dr Neal has received research support from the Australian National Health and Medical Research Council Principal Research Fellowship and from Janssen, Roche, Servier, and Merck Schering-Plough; and has served on advisory boards and/or has been involved in continuing medical education programs for Abbott, Janssen, Novartis, Pfizer, Roche, and Servier, with any consultancy, honoraria, or travel support paid to his institution. Dr Matthews has received research support from Janssen; served on advisory boards and as a consultant for Novo Nordisk, Novartis, Sanofi-Aventis, Janssen, and Servier; and has given lectures for Novo Nordisk, Servier, Sanofi-Aventis, Novartis, Janssen, Mitsubishi Tanabe, and Aché Laboratories. Dr de Zeeuw has served on advisory boards and/or as a speaker for AbbVie, Astellas, Fresenius, Janssen, Boehringer Ingelheim, Bayer, and Mitsubishi Tanabe, with all consultancy honoraria paid to his institution. Dr Mahaffey’s disclosures can be viewed at http://med.stanford.edu/profiles/kenneth-mahaffey. Dr Fulcher has received research support from Novo Nordisk, and served on advisory boards and as a consultant for Janssen, Novo Nordisk, Boehringer Ingelheim, and Merck Sharp & Dohme. Drs Desai and Rosenthal and H. Deng are full-time employees of Janssen Research & Development, LLC, and hold stock in Johnson & Johnson. Dr Jardine is supported by a Medical Research Future Fund Next Generation Clinical Researchers Program Career Development Fellowship; is responsible for research projects that have received unrestricted funding from Gambro, Baxter, CSL, Amgen, Eli Lilly, and Merck; has served on advisory boards sponsored by Akebia, Baxter, and Boehringer Ingelheim; and has spoken at scientific meetings sponsored by Jans-sen, Amgen, and Roche with any consultancy, honoraria, or travel support paid to her institution. Dr Bakris has received research funding paid to the University of Chicago for Bayer, Janssen, and Vascular Dynamics; has served as a consultant for Merck and Relypsa; and has served as Editor-in-Chief for American Journal of Nephrology, as the Nephrology and Hypertension Section Editor for UpToDate, as Section Editor of Hypertension, and as associate editor of Diabetes Care and Hypertension Research. Dr Perkovic has received research support from the Australian National Health and Medical Research Council (Senior Research Fellowship and Program Grant); served on Steering Committees for AbbVie, Boehringer Ingelheim, GlaxoSmithKline, Janssen, and Pfizer; and served on advisory boards and/or spoken at scientific meetings for AbbVie, Astellas, AstraZeneca, Bayer, Baxter, Bristol-Myers Squibb, Boehringer Ingelheim, Durect, Eli Lilly, Gilead, Glaxo-SmithKline, Janssen, Merck, Novartis, Novo Nordisk, Pfizer, Pharmalink, Relypsa, Roche, Sanofi, Servier, and Vitae, with all honoraria paid to his employer.
Publisher Copyright:
© 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.
PY - 2018
Y1 - 2018
N2 - 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, 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 CANVAS Program randomized 10 142 participants with type 2 diabetes and eGFR >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 chronic kidney disease, defined as eGFR <60 and ≥60 mL/min/1.73 m2, and according to baseline kidney function (eGFR <45, 45 to <60, 60 to <90, and ≥90 mL/min/1.73 m2). RESULTS: At baseline, 2039 (20.1%) participants had an eGFR <60 mL/min/1.73 m2, 71.6% of whom had a history of cardiovascular disease. The effect of canagliflozin on the primary outcome was similar in people with chronic kidney disease (hazard ratio, 0.70; 95% CI, 0.55-0.90) and those with preserved kidney function (hazard ratio, 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 effects of canagliflozin on cardiovascular and renal outcomes were 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 chronic kidney disease may allow additional individuals to benefit from this therapy.
AB - 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, 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 CANVAS Program randomized 10 142 participants with type 2 diabetes and eGFR >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 chronic kidney disease, defined as eGFR <60 and ≥60 mL/min/1.73 m2, and according to baseline kidney function (eGFR <45, 45 to <60, 60 to <90, and ≥90 mL/min/1.73 m2). RESULTS: At baseline, 2039 (20.1%) participants had an eGFR <60 mL/min/1.73 m2, 71.6% of whom had a history of cardiovascular disease. The effect of canagliflozin on the primary outcome was similar in people with chronic kidney disease (hazard ratio, 0.70; 95% CI, 0.55-0.90) and those with preserved kidney function (hazard ratio, 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 effects of canagliflozin on cardiovascular and renal outcomes were 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 chronic kidney disease may allow additional individuals to benefit from this therapy.
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U2 - 10.1161/CIRCULATIONAHA.118.035901
DO - 10.1161/CIRCULATIONAHA.118.035901
M3 - Article
C2 - 29941478
AN - SCOPUS:85053770094
SN - 0009-7322
VL - 138
SP - 1537
EP - 1550
JO - Circulation
JF - Circulation
IS - 15
ER -
