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Canagliflozin and Cardiovascular and Renal Outcomes in Type 2 Diabetes and Chronic Kidney Disease in Primary and Secondary Cardiovascular Prevention Groups: Results From the Randomized CREDENCE Trial

Mahaffey, KW; Jardine, M; Bompoint, S; Cannon, C; Bruce, N; Herspink, LHJ; Charytan, D; ... Perkovic, V; + view all (2019) Canagliflozin and Cardiovascular and Renal Outcomes in Type 2 Diabetes and Chronic Kidney Disease in Primary and Secondary Cardiovascular Prevention Groups: Results From the Randomized CREDENCE Trial. Circulation , 140 (9) pp. 739-750. 10.1161/CIRCULATIONAHA.119.042007. Green open access

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Abstract

Background Canagliflozin reduces the risk of kidney failure in patients with type 2 diabetes and chronic kidney disease, but effects on specific cardiovascular outcomes are uncertain, as are effects in people without prior cardiovascular disease (primary prevention). Methods In CREDENCE, 4401 participants with type 2 diabetes and chronic kidney disease were randomly assigned to canagliflozin or placebo on a background of optimized standard of care. Results Primary prevention participants (N=2181; 49.6%) were younger (61 vs 65 years), more often female (37% vs 31%), and had shorter diabetes duration (15 vs 16 years) compared to secondary prevention participants (N=2220; 50.4%). Canagliflozin reduced the risk of major cardiovascular events overall (hazard ratio [HR], 0.80; 95% confidence interval [CI] 0.67–0.95; P=0.01), with consistent reductions in both the primary (HR, 0.68; 95% CI, 0.49–0.94) and secondary (HR, 0.85; 95% CI, 0.69–1.06) prevention groups (P-interaction 0.25). Effects were also similar for the components of the composite including cardiovascular death (HR, 0.78; 95% CI, 0.61–1.00), nonfatal myocardial infarction (HR, 0.81; 95% CI, 0.59–1.10), and nonfatal stroke (HR, 0.80; 95% CI, 0.56–1.15). The risk of the primary composite renal outcome and the composite of cardiovascular death or hospitalization for heart failure were also consistently reduced in both the primary and secondary prevention groups (P-interaction >0.5 for each outcome). Conclusions Canagliflozin significantly reduced major cardiovascular events, as well as kidney failure, in patients with type 2 diabetes and chronic kidney disease, including in participants who did not have prior cardiovascular disease.

Type: Article
Title: Canagliflozin and Cardiovascular and Renal Outcomes in Type 2 Diabetes and Chronic Kidney Disease in Primary and Secondary Cardiovascular Prevention Groups: Results From the Randomized CREDENCE Trial
Open access status: An open access version is available from UCL Discovery
DOI: 10.1161/CIRCULATIONAHA.119.042007
Publisher version: https://doi.org/10.1161/CIRCULATIONAHA.119.042007
Language: English
Additional information: © 2019 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, primary prevention, secondary prevention, cardiovascular outcomes, clinical trial, diabetes mellitus, chronic kidney disease
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Renal Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/10076979
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