The effect of metformin on patient outcome after acute myocardial infarction

Date of ISAC Approval: 
Lay Summary: 
Coronary heart disease, including heart attacks, remains the biggest cause of death worldwide. It is recognised that promptly opening the blocked coronary artery that causes a heart attack is the best available treatment. However, this therapeutic restoration of blood-flow, in combination with the preceding ischaemia, may contribute to the final heart attack size. As such, this provides an important target for protection against so-called 'ischaemia-reperfusion injury' (IRI). Several drugs have been targeted at IRI. Recently, several animal studies have suggested that metformin, a medication commonly prescribed for type 2 diabetes mellitus, may be valuable in this regard. However, randomised clinical trials of metformin administered in advance of a heart attack are not possible given the unpredictable nature of the disease. Furthermore, any beneficial effect remains to be tested in large observational studies. Examining data from adult patients within the CPRD who have suffered a heart attack, some of who will have been taking metformin at the time, will provide a unique insight into the potential favourable effects of metformin in the context of IRI. If the laboratory data is supported by observational data from the CPRD, it presents a new and exciting opportunity for reducing the burden of cardiovascular disease.
Technical Summary: 
The objective of the proposed research is to investigate the effect of preadmission and subsequent metformin on outcomes after acute myocardial infarction (AMI) in type 2 diabetics using CPRD data linked with the national audit of myocardial infarction (MINAP), Office for National Statistics (ONS) mortality data and hospital episode statistics (HES) data through the CALIBER dataset. This is a prospective cohort study of patients with type 2 diabetes experiencing their first AMI, comparing patients with a prescription of metformin (or metformin and other oral anti-diabetic agents) versus alternative oral anti-diabetic medication without metformin prior to, and after, index AMI. Patients will be compared with respect to primary outcomes of major adverse cardiac events (a composite of cardiovascular death, acute coronary syndrome requiring hospitalisation, and stroke), heart failure and all-cause mortality. The absolute incidence of AMI, demographic and baseline characteristics of the study population with or without metformin will be compared using the Pearson Chi Square test for categorical variables and Student t test for continuous variables. We will calculate Kaplan-Meier product limits for cumulative probability of reaching an end point and use the log rank test for evidence of a significant difference between groups. Cox regression analysis will be used to estimate hazard ratios for the effect of metformin in fully adjusted models.
Health Outcomes to be Measured: 
Major adverse cardiac events All-cause mortality Heart failure admissions

Professor Derek Yellon - Chief Investigator - University College London (UCL)
Dr Daniel Bromage - Corresponding Applicant - King's College London
Dr Emily Herrett - Researcher - London School of Hygiene & Tropical Medicine (LSHTM)
Professor Harry Hemingway - Researcher - University College London (UCL)
Dr Mar Pujades Rodriguez - Researcher - IQVIA - UK
Dr Xavier Rossello Lozano - Researcher - University College London (UCL)

HES Admitted;MINAP;ONS;Patient IMD;Patient Townsend;Practice IMD (Standard)