Abstract
BackgroundThe 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.MethodsThis 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.Results4,030 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).ConclusionsOur 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.
Highlights
The use of metformin after acute myocardial infarction (AMI) has been associated with reduced mortal‐ ity in people with type 2 diabetes mellitus (T2DM)
A mortality benefit of pre-treatment with metformin has not been demonstrated in patients with AMI and, using linked electronic health records from the CALIBER resource, which prospectively records medication status, we investigated whether metformin administration is associated with cardioprotection to these patients
Metformin use and patient baseline characteristics Out of 4,703,682 patients in CALIBER, we identified 4030 eligible patients with T2DM and no history of heart failure (HF) or AMI, who had an incident AMI during the study period (Fig. 1)
Summary
The use of metformin after acute myocardial infarction (AMI) has been associated with reduced mortal‐ ity in people with type 2 diabetes mellitus (T2DM). It is not known if it is acutely cardioprotective in patients taking metformin at the time of AMI. (UKPDS) was a large randomised, multicentre trial of glycaemic therapies in patients with newly diagnosed type 2 diabetes mellitus (T2DM) [8]. It showed lower risk of AMI in metformin users than in participants on diet therapy alone. The role of metformin in reducing cardiovascular disease remains controversial, with no cardiovascular outcomes achieving statistical significance in a recent meta-analysis [10]
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