TY - JOUR
T1 - Effect of Canagliflozin on Total Cardiovascular Burden in Patients With Diabetes and Chronic Kidney Disease
T2 - A Post Hoc Analysis From the CREDENCE Trial
AU - Li, Jing Wei
AU - Arnott, Clare
AU - Heerspink, Hiddo J.L.
AU - Mbiostat, Qiang Li
AU - Cannon, Christopher P.
AU - Wheeler, David C.
AU - Charytan, David M.
AU - Barraclough, Jennifer
AU - Figtree, Gemma A.
AU - Agarwal, Rajiv
AU - Bakris, George
AU - de Zeeuw, Dick
AU - Greene, Tom
AU - Levin, Adeera
AU - Pollock, Carol
AU - Zhang, Hong
AU - Zinman, Bernard
AU - Mahaffey, Kenneth W.
AU - Perkovic, Vlado
AU - Neal, Bruce
AU - Jardine, Meg J.
N1 - Funding Information:
Dr Arnott is supported by an National Health and Medical Research Council/ Medical Research Future Fund Priority Investigator Grant and a New South Wales Health Early-Mid Career Research Grant. She is an employee of the George Institute for Global Health. She has received honoraria from Amgen. Dr Cannon has received research grants from Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Merck, Janssen, and Takeda; and has received consulting fees from Aegerion, Alnylam, Amarin, Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Corvidia, GlaxoSmithKline, Innovent, Eisai, Eli Lilly, Kowa, Merck, Pfizer, Regeneron, and Sanofi. Dr Zeeuw reports serving on advisory boards and as a speaker for Bayer, Boehringer Ingelheim, Fresenius, Mundipharma, and Mitsubishi Tanabe; serving on Steering Committees and as a speaker for AbbVie and Janssen; and serving on Data Safety and Monitoring Committees for Bayer. Dr Heerspink has served as a consultant for Abbvie, Astellas, AstraZeneca, Boehringer Ingelheim, Fresenius, Gilead, Janssen, Merck, and Mitsubishi-Tanabe and has received grant support from Abbvie, AstraZeneca, Boehringer Ingelheim, and Janssen. Dr Charytan has served on clinical events committees or data safety and monitoring boards for PLC Medical, AstraZeneca, Allena Pharmaceuticals, and Merck; served on steering committees for Zoll Medical and Janssen Pharmaceuticals; and reported consulting fees or travel fees from Daichi Sankyo, Fresenius, and Medtronic/ Coviden. He was on the steering committee for the kidney outcome trial of an SGLT2 inhibitor (canagliflozin; CREDENCE, 43 NCT02065791). Dr Barraclough is supported by a New South Wales Health Early-Mid Career Research Grant and is an employee of the George Institute for Global Health. Dr Figtree reports receiving research support from the cofunded National Health and Medical Research Council and Heart Foundation (Australia) Practitioner Fellowship and the Heart Research Australia, and compensation from Janssen for serving on the Adjudication 1 Panel of the CANVAS program. Dr Bakris works for the University of Chicago Medicine. He is a consultant for Merck, Bayer, Vascular Dynamics, KBP Biosciences, Ionis, Alnylam, and Astra Zeneca. He has research support and is on the steering committee of trials for Bayer and Vascular Dynamics. He is the editor of the American Journal of Nephrology.
Funding Information:
CREDENCE was sponsored by Janssen Research & Development, LLC.
Publisher Copyright:
© 2022 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.
PY - 2022/8/16
Y1 - 2022/8/16
N2 - BACKGROUND: The sodium-glucose cotransporter 2 inhibitor canagliflozin reduced the risk of first cardiovascular composite events in the CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) trial. In this post hoc analysis, we evaluated the effect of canagliflozin on total (first and recurrent) cardiovascular events.METHODS AND RESULTS: The CREDENCE trial compared canagliflozin or matching placebo in 4401 patients with type 2 diabetes, albuminuria, and estimated glomerular filtration rate of 30 to <90 mL/min per 1.73 m2, over a median of 2.6 years. The primary outcome was analyzed as a composite of any cardiovascular event including myocardial infarction, stroke, hospitalization for heart failure, hospitalization for unstable angina, and cardiovascular death. Negative binomial regression models were used to assess the effect of canagliflozin on the net burden of cardiovascular events. During the trial, 634 patients had 883 cardiovascular events, of whom 472 (74%) had just 1 cardiovascular event and 162 (26%) had multiple cardiovascular events. Canagliflozin reduced first cardiovascular events by 26% (hazard ratio, 0.74 [95% CI, 0.63– 0.86]; P<0.001) and total cardiovascular events by 29% (incidence rate ratio, 0.71 [95% CI, 0.59– 0.86]; P<0.001). The absolute risk difference per 1000 patients treated over 2.5 years was −44 (95% CI, −67 to −21) first cardiovascular events and −73 (95% CI, −114 to −33) total events.CONCLUSIONS: Canagliflozin reduced cardiovascular events, with a larger absolute benefit for total cardiovascular than first cardiovascular events. These findings provide further support for the benefit of continuing canagliflozin therapy after an initial event to prevent recurrent cardiovascular events.
AB - BACKGROUND: The sodium-glucose cotransporter 2 inhibitor canagliflozin reduced the risk of first cardiovascular composite events in the CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) trial. In this post hoc analysis, we evaluated the effect of canagliflozin on total (first and recurrent) cardiovascular events.METHODS AND RESULTS: The CREDENCE trial compared canagliflozin or matching placebo in 4401 patients with type 2 diabetes, albuminuria, and estimated glomerular filtration rate of 30 to <90 mL/min per 1.73 m2, over a median of 2.6 years. The primary outcome was analyzed as a composite of any cardiovascular event including myocardial infarction, stroke, hospitalization for heart failure, hospitalization for unstable angina, and cardiovascular death. Negative binomial regression models were used to assess the effect of canagliflozin on the net burden of cardiovascular events. During the trial, 634 patients had 883 cardiovascular events, of whom 472 (74%) had just 1 cardiovascular event and 162 (26%) had multiple cardiovascular events. Canagliflozin reduced first cardiovascular events by 26% (hazard ratio, 0.74 [95% CI, 0.63– 0.86]; P<0.001) and total cardiovascular events by 29% (incidence rate ratio, 0.71 [95% CI, 0.59– 0.86]; P<0.001). The absolute risk difference per 1000 patients treated over 2.5 years was −44 (95% CI, −67 to −21) first cardiovascular events and −73 (95% CI, −114 to −33) total events.CONCLUSIONS: Canagliflozin reduced cardiovascular events, with a larger absolute benefit for total cardiovascular than first cardiovascular events. These findings provide further support for the benefit of continuing canagliflozin therapy after an initial event to prevent recurrent cardiovascular events.
KW - canagliflozin
KW - chronic kidney disease
KW - diabetes
KW - recurrent cardiovascular event
U2 - 10.1161/JAHA.121.025045
DO - 10.1161/JAHA.121.025045
M3 - Article
C2 - 35929472
AN - SCOPUS:85136111290
SN - 2047-9980
VL - 11
JO - Journal of the American Heart Association
JF - Journal of the American Heart Association
IS - 16
M1 - e025045
ER -