Effects of oral glucose-lowering drugs on long term outcomes in patients with diabetes mellitus following myocardial infarction not treated with emergent percutaneous coronary intervention - a retrospective nationwide cohort study

BACKGROUND The optimum oral pharmacological treatment of diabetes mellitus to reduce cardiovascular disease and mortality following myocardial infarction has not been established. We therefore set out to investigate the association between individual oral glucose-lowering drugs and cardiovascular outcomes following myocardial infarction in patients with diabetes mellitus not treated with emergent percutaneous coronary intervention. MATERIALS AND METHODS All patients aged 30 years or older receiving glucose-lowering drugs (GLDs) and admitted with myocardial infarction (MI) not treated with emergent percutaneous coronary intervention in Denmark during 1997-2006 were identified by individual-level linkage of nationwide registries of hospitalizations and drug dispensing from pharmacies. Multivariable Cox regression models adjusted for age, sex, calendar year, comorbidity, and concomitant pharmacotherapy were used to assess differences in the composite endpoint of non-fatal MI and cardiovascular mortality between individual GLDs, using metformin monotherapy as reference. RESULTS The study comprised 9876 users of GLDs admitted with MI. The mean age was 72.3 years and 56.5% of patients were men. A total of 3649 received sulfonylureas and 711 received metformin at admission. The average length of follow-up was 2.2 (SD 2.6) years. A total of 6,171 patients experienced the composite study endpoint. The sulfonylureas glibenclamide, glimepiride, glipizide, and tolbutamide were associated with increased risk of cardiovascular mortality and/or nonfatal MI with hazard ratios [HRs] of 1.31 (95% confidence interval [CI] 1.17-1.46), 1.19 (1.06-1.32), 1.25 (1.11-1.42), and 1.18 (1.03-1.34), respectively, compared with metformin. Gliclazide was the only sulfonylurea not associated with increased risk compared with metformin (HR 1.03 [0.88-1.22]). CONCLUSIONS In patients with diabetes mellitus admitted with MI not treated with emergent percutaneous coronary intervention, monotherapy treatment with the sulfonylureas glibenclamide, glimepiride, glipizide, and tolbutamide was associated with increased cardiovascular risk compared with metformin monotherapy.