Canagliflozin and atrial fibrillation in type 2 diabetes mellitus: A secondary analysis from the CANVAS Program and CREDENCE trial and meta-analysis.

Chao Li, Jie Yu, Carinna Hockham, Vlado Perkovic, Brendon L Neuen, Sunil V Badve, Lauren Houston, Vivian Y J Lee, Jennifer Y Barraclough, Robert A Fletcher, Kenneth W Mahaffey, Hiddo J L Heerspink, Christopher P Cannon, Bruce Neal, Clare Arnott

Journal: Diabetes, obesity & metabolism 2022;24(10):1927-1938

PMID: 35589614

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Abstract

AIM

To assess the effects of canagliflozin on the incidence of atrial fibrillation/atrial flutter (AF/AFL) and other key cardiorenal outcomes in a pooled analysis of the CANVAS and CREDENCE trials.

MATERIALS AND METHODS

Participants with type 2 diabetes 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 (ischaemic stroke/transient ischaemic attack/hospitalization for heart failure). Major adverse cardiovascular events 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 (hazard ratio [HR] 0.82, 95% confidence interval [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 P > 0.14). Meta-analysis of five sodium-glucose cotransporter-2 (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.

Address: Cardiovascular Centre, Beijing Tongren Hospital, Capital Medical University, Beijing, China.; The George Institute for Global Health, UNSW Sydney, Sydney, New South Wales, Australia.; Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia.; Department of Cardiology, Peking University Third Hospital, Beijing, China.; The George Institute for Global Health, School of Public Health, Imperial College London, London, UK.; The Royal North Shore Hospital, Sydney, New South Wales, Australia.; Department of Nephrology, St George Hospital, Sydney, Australia.; Stanford Center for Clinical Research, Department of Medicine, Stanford University School of Medicine, Stanford, California, USA.; Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.; Cardiovascular Division, Brigham & Women's Hospital and Baim Institute for Clinical Research, Boston, Massachusetts, USA.; Imperial College London, London, UK.; Department of Cardiology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia.; Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia.

DOI: 10.1111/dom.14772

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MeSH Terms: Atrial Fibrillation, Atrial Flutter, Brain Ischemia, Canagliflozin, Diabetes Mellitus, Type 2, Humans, Sodium-Glucose Transporter 2, Stroke