Cardiovascular and renal outcomes with canagliflozin in patients with peripheral arterial disease: Data from the CANVAS Program and CREDENCE trial

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 P interaction > .268). There was no increase in the relative risk of extended MALE with canagliflozin, irrespective of baseline PAD history ( P interaction > .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.