Effects of canagliflozin on myocardial infarction: a post hoc analysis of the CANVAS programme and CREDENCE trial

Author:

Yu Jie12ORCID,Li Jingwei1,Leaver Phillip J3ORCID,Arnott Clare1456ORCID,Huffman Mark D17ORCID,Udell Jacob A8ORCID,Perkovic Vlado16,Mahaffey Kenneth W9,de Zeeuw Dick10,Fulcher Greg5ORCID,Matthews David R11ORCID,Shaw Wayne12,Rosenthal Norman12ORCID,Neal Bruce11314ORCID,Figtree Gemma A135

Affiliation:

1. The George Institute for Global Health, UNSW Sydney, Level 5, 1 King Street, Newtown, 2042 Sydney, Australia

2. Department of Cardiology, Peking University Third Hospital, Level 5, 1 King Street, Newtown, 2042 Beijing, China

3. Kolling Institute, Royal North Shore Hospital and University of Sydney, Pacific Highway St Leonards, 2065 Sydney, Australia

4. Department of Cardiology, Royal Prince Alfred Hospital, 50 Missenden Road, Camperdown 2050 Sydney, Australia

5. Sydney Medical School, University of Sydney, Camperdown, 2050 Sydney, Australia

6. Faculty of Medicine, University of New South Wales, 18 High Street, Kensington 2052 Sydney, Australia

7. Department of Preventive Medicine and Centre for Global Cardiovascular Health, Northwestern University Feinberg School of Medicine, Chicago, IL, USA

8. Department of Medicine, Cardiovascular Division, Peter Munk Cardiac Centre, Toronto General Hospital and Women’s College Hospital, University of Toronto, Toronto, ON, Canada

9. Stanford Center for Clinical Research, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA

10. Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands

11. Oxford Centre for Diabetes, Endocrinology and Metabolism and Harris Manchester College, University of Oxford, Mansfield Road, Oxford OX1 3TD, UK

12. Janssen Research & Development, LLC, 920 US-202, Raritan, NJ 08869, USA

13. The Charles Perkins Centre, University of Sydney, John Hopkins Drive, 2006 Sydney, Australia

14. Faculty of Clinical Epidemiology, Imperial College London, Level 2, Faculty Building South Kensington Campus, SW7 2AZ London, UK

Abstract

Abstract Aims Given the benefits of sodium glucose co-transporter 2 inhibition (SGLT2i) in protecting against heart failure in diabetic patients, we sought to explore the potential impact of SGLT2i on the clinical features of patients presenting with myocardial infarction (MI) through a post hoc analysis of CANVAS Programme and CREDENCE trial. Methods and results Individuals with type 2 diabetes and history or high risk of cardiovascular disease (CANVAS Programme) or type 2 diabetes and chronic kidney disease (CREDENCE) were included. The intervention was canagliflozin 100 or 300 mg (combined in the analysis) or placebo. MI events were adjudicated as ST-elevation myocardial infarction (STEMI), non-STEMI, and type 1 MI or type 2 MI. A total of 421 first MI events in the CANVAS Programme and 178 first MI events in the CREDENCE trial were recorded (83 fatal, 128 STEMI, 431 non-STEMI, and 40 unknown). No benefit of canagliflozin compared with placebo on time to first MI event was observed [hazard ratio (HR) 0.89; 95% confidence interval (CI) 0.75, 1.05]. Canagliflozin was associated with lower risk for non-STEMI (HR 0.78; 95% CI 0.65, 0.95) but suggested a possible increase in STEMI (HR 1.55; 95% CI 1.06, 2.27), with no difference in risk of type 1 or type 2 MI. There was no change in fatal MI (HR 1.22, 95% CI 0.78, 1.93). Conclusion Canagliflozin was not associated with a reduction in overall MI in the pooled CANVAS Programme and CREDENCE trial population. The possible differential effect on STEMI and Non-STEMI observed in the CANVAS cohort warrants further investigation. Trial registration ClinicalTrials.gov identifiers: NCT01032629, NCT01989754, and NCT02065791.

Funder

Janssen Research & Development, LLC

National Health and Medical Research Council Practitioner Fellowship

Publisher

Oxford University Press (OUP)

Subject

Physiology (medical),Cardiology and Cardiovascular Medicine,Physiology

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