Daniel I Bromage1,2, Tom R Godec3, Mar Pujades-Rodriguez4, Arturo Gonzalez-Izquierdo5,6,7, S Denaxas5,6,7, Harry Hemingway5,6,7, Derek M Yellon8. 1. The Hatter Cardiovascular Institute, University College London, 67 Chenies Mews, London, WC1E 6HX, UK. 2. School of Cardiovascular Medicine and Sciences, King's College London British Heart Foundation Centre of Excellence, James Black Centre, 125 Coldharbour Lane, London, SE5 9NU, UK. 3. The London School of Hygiene & Tropical Medicine, Keppel St, London, WC1E 7HT, UK. 4. Leeds Institute of Health Sciences, University of Leeds, Clarendon Way, Leeds, LS2 9JL, UK. 5. Institute of Health Informatics, University College London, 222 Euston Road, London, NW1 2DA, UK. 6. Health Data Research UK London, University College London, 222 Euston Road, London, NW1 2DA, UK. 7. The National Institute for Health Research University College London Hospitals Biomedical Research Centre, University College London, 222 Euston Road, London, NW1 2DA, UK. 8. The Hatter Cardiovascular Institute, University College London, 67 Chenies Mews, London, WC1E 6HX, UK. d.yellon@ucl.ac.uk.
Abstract
BACKGROUND: The use of metformin after acute myocardial infarction (AMI) has been associated with reduced mortality in people with type 2 diabetes mellitus (T2DM). However, it is not known if it is acutely cardioprotective in patients taking metformin at the time of AMI. We compared patient outcomes according to metformin status at the time of admission for fatal and non-fatal AMI in a large cohort of patients in England. METHODS: This study used linked data from primary care, hospital admissions and death registry from 4.7 million inhabitants in England, as part of the CALIBER resource. The primary endpoint was a composite of acute myocardial infarction requiring hospitalisation, stroke and cardiovascular death. The secondary endpoints were heart failure (HF) hospitalisation and all-cause mortality. RESULTS: 4,030 patients with T2DM and incident AMI recorded between January 1998 and October 2010 were included. At AMI admission, 63.9% of patients were receiving metformin and 36.1% another oral hypoglycaemic drug. Median follow-up was 343 (IQR: 1-1436) days. Adjusted analyses showed an increased hazard of the composite endpoint in metformin users compared to non-users (HR 1.09 [1.01-1.19]), but not of the secondary endpoints. The higher risk of the composite endpoint in metformin users was only observed in people taking metformin at AMI admission, whereas metformin use post-AMI was associated with a reduction in risk of all-cause mortality (0.76 [0.62-0.93], P = 0.009). CONCLUSIONS: Our study suggests that metformin use at the time of first AMI is associated with increased risk of cardiovascular disease and death in patients with T2DM, while its use post-AMI might be beneficial. Further investigation in well-designed randomised controlled trials is indicated, especially in view of emerging evidence of cardioprotection from sodium-glucose co-transporter-2 (SGLT2) inhibitors.
BACKGROUND: The use of metformin after acute myocardial infarction (AMI) has been associated with reduced mortality in people with type 2 diabetes mellitus (T2DM). However, it is not known if it is acutely cardioprotective in patients taking metformin at the time of AMI. We compared patient outcomes according to metformin status at the time of admission for fatal and non-fatal AMI in a large cohort of patients in England. METHODS: This study used linked data from primary care, hospital admissions and death registry from 4.7 million inhabitants in England, as part of the CALIBER resource. The primary endpoint was a composite of acute myocardial infarction requiring hospitalisation, stroke and cardiovascular death. The secondary endpoints were heart failure (HF) hospitalisation and all-cause mortality. RESULTS: 4,030 patients with T2DM and incident AMI recorded between January 1998 and October 2010 were included. At AMI admission, 63.9% of patients were receiving metformin and 36.1% another oral hypoglycaemic drug. Median follow-up was 343 (IQR: 1-1436) days. Adjusted analyses showed an increased hazard of the composite endpoint in metformin users compared to non-users (HR 1.09 [1.01-1.19]), but not of the secondary endpoints. The higher risk of the composite endpoint in metformin users was only observed in people taking metformin at AMI admission, whereas metformin use post-AMI was associated with a reduction in risk of all-cause mortality (0.76 [0.62-0.93], P = 0.009). CONCLUSIONS: Our study suggests that metformin use at the time of first AMI is associated with increased risk of cardiovascular disease and death in patients with T2DM, while its use post-AMI might be beneficial. Further investigation in well-designed randomised controlled trials is indicated, especially in view of emerging evidence of cardioprotection from sodium-glucose co-transporter-2 (SGLT2) inhibitors.
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Authors: Anoop Dinesh Shah; Claudia Langenberg; Eleni Rapsomaniki; Spiros Denaxas; Mar Pujades-Rodriguez; Chris P Gale; John Deanfield; Liam Smeeth; Adam Timmis; Harry Hemingway Journal: Lancet Date: 2015-02-26 Impact factor: 79.321
Authors: Thomas R Godec; Daniel I Bromage; Mar Pujades-Rodriguez; Antonio Cannatà; Arturo Gonzalez-Izquierdo; Spiros Denaxas; Harry Hemingway; Ajay M Shah; Derek M Yellon; Theresa A McDonagh Journal: ESC Heart Fail Date: 2022-03-23