Cardiovascular and renal outcomes with canagliflozin in patients with peripheral arterial disease: Data from the CANVAS Program and CREDENCE trial
Author(s)
Type
Journal Article
Abstract
Aim
To define the proportional and absolute benefits of the sodium-glucose co-transporter-2 inhibitor canagliflozin in patients with type 2 diabetes (T2D) with and without peripheral arterial disease (PAD).
Materials and Methods
We pooled individual participant data from the CANVAS Program (n = 10 142) and CREDENCE trial (n = 4401). In this post hoc analysis, the main outcomes of interest were major adverse cardiovascular events (MACE: non-fatal myocardial infarction, non-fatal stroke or cardiovascular death), kidney outcomes, and extended major adverse limb events (MALE). Cox proportional hazards models were used to assess canagliflozin treatment effects in those with and without PAD. Absolute risk reductions per 1000 patients treated for 2.5 years were estimated using Poisson regression.
Results
Of 14 543 participants, 3159 (21.7%) had PAD at baseline. In patients with PAD, canagliflozin reduced MACE (hazard ratio, 0.76; 95% confidence interval, 0.62-0.92), with similar relative benefits for other cardiovascular and kidney outcomes in participants with or without PAD at baseline (all Pinteraction > .268). There was no increase in the relative risk of extended MALE with canagliflozin, irrespective of baseline PAD history (Pinteraction > .864). The absolute benefits of canagliflozin were greater in those with PAD.
Conclusions
Patients with T2D and PAD derived similar relative cardiorenal benefits from canagliflozin treatment but higher absolute benefits compared with those without PAD, with no increase in extended MALE.
To define the proportional and absolute benefits of the sodium-glucose co-transporter-2 inhibitor canagliflozin in patients with type 2 diabetes (T2D) with and without peripheral arterial disease (PAD).
Materials and Methods
We pooled individual participant data from the CANVAS Program (n = 10 142) and CREDENCE trial (n = 4401). In this post hoc analysis, the main outcomes of interest were major adverse cardiovascular events (MACE: non-fatal myocardial infarction, non-fatal stroke or cardiovascular death), kidney outcomes, and extended major adverse limb events (MALE). Cox proportional hazards models were used to assess canagliflozin treatment effects in those with and without PAD. Absolute risk reductions per 1000 patients treated for 2.5 years were estimated using Poisson regression.
Results
Of 14 543 participants, 3159 (21.7%) had PAD at baseline. In patients with PAD, canagliflozin reduced MACE (hazard ratio, 0.76; 95% confidence interval, 0.62-0.92), with similar relative benefits for other cardiovascular and kidney outcomes in participants with or without PAD at baseline (all Pinteraction > .268). There was no increase in the relative risk of extended MALE with canagliflozin, irrespective of baseline PAD history (Pinteraction > .864). The absolute benefits of canagliflozin were greater in those with PAD.
Conclusions
Patients with T2D and PAD derived similar relative cardiorenal benefits from canagliflozin treatment but higher absolute benefits compared with those without PAD, with no increase in extended MALE.
Date Issued
2022-06
Date Acceptance
2022-02-11
Citation
Diabetes, Obesity and Metabolism: a journal of pharmacology and therapeutics, 2022, 24 (6), pp.1072-1083
ISSN
1462-8902
Publisher
Wiley
Start Page
1072
End Page
1083
Journal / Book Title
Diabetes, Obesity and Metabolism: a journal of pharmacology and therapeutics
Volume
24
Issue
6
Copyright Statement
© 2022 John Wiley & Sons Ltd. This is the accepted version of the following article: Barraclough, JY, Yu, J, Figtree, GA, et al. Cardiovascular and renal outcomes with canagliflozin in patients with peripheral arterial disease: Data from the CANVAS Program and CREDENCE trial. Diabetes Obes Metab. 2022; 1- 12, which has been published in final form at https://doi.org/10.1111/dom.14671
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000765583500001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Life Sciences & Biomedicine
Endocrinology & Metabolism
antidiabetic drug
canagliflozin
cardiovascular disease
clinical trial
BASE-LINE CHARACTERISTICS
RISK-FACTORS
RATIONALE
DESIGN
EPIDEMIOLOGY
PREVALENCE
MORTALITY
INSIGHTS
Publication Status
Published
Date Publish Online
2022-02-15