Canagliflozin and Atrial Fibrillation in Type 2 Diabetes Mellitus: A secondary analysis from the CANVAS Program and CREDENCE trials and meta-analysis

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Diabetes Obes Metab. 2022 May 19. doi: 10.1111/dom.14772. Online ahead of print.


AIMS: The effect of sodium-glucose co-transporter 2 inhibitors on atrial fibrillation/flutter (AF/AFL) is unclear. We assessed the effects of canagliflozin on the incidence of AF/AFL and other key cardiorenal outcomes in a pooled analysis of the CANVAS and CREDENCE trials.

MATERIALS AND METHODS: Participants with T2D and high risk of cardiovascular disease or chronic kidney disease were included and randomly assigned to canagliflozin or placebo. We explored the effects of canagliflozin on the incidence of first AF/AFL events and AF/AFL related complications (ischemic stroke/transient ischemic attack/hospitalisation for heart failure). Major adverse cardiovascular events (MACE), and a renal-specific outcome by baseline AF/AFL status were analysed using Cox regression models.

RESULTS: Overall 354 participants experienced a first AF/AFL event. Canagliflozin had no detectable effect on AF/AFL (HR 0.82; 95% CI, 0.67, 1.02) compared with placebo. Subgroup analysis, however, suggested a possible reduction in AF/AFL in those with no AF/AFL history (HR 0.78; 95% CI, 0.62, 0.99). Canagliflozin was also associated with a reduction in AF/AFL related complications (HR 0.74; 95% CI, 0.65, 0.86). There was no evidence of treatment heterogeneity by baseline AF/AFL history for other key cardiorenal outcomes (all Pinteraction >0.14). Meta-analysis of five SGLT2 inhibitor trials demonstrated a 19% reduction in AF/AFL events with active treatment (HR 0.81; 95% CI 0.72, 0.92).

CONCLUSIONS: Overall, a significant effect of canagliflozin on the incidence of AF/AFL events could not be shown, however, a possible reduction in AF/AFL events in those with no prior history requires further investigation. Meta-analysis suggests SGLT2 inhibition reduces AF/AFL incidence. This article is protected by copyright. All rights reserved.

PMID:35589614 | DOI:10.1111/dom.14772