Cardiovascular outcomes in patients who experienced a myocardial infarction while treated with liraglutide versus placebo in the LEADER trial

Abstract

Objective: Animal studies demonstrated that glucagon-like peptide-1 receptor agonists reduce myocardial necrosis following regional ischaemia induction. This effect may improve cardiovascular outcomes after myocardial infarction. Risk of cardiovascular death or hospitalisation for heart failure after myocardial infarction was evaluated in patients with type 2 diabetes at high cardiovascular risk in the LEADER trial.

Methods: Data from patients randomised to liraglutide or placebo, in addition to standard of care, in Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) (NCT01179048) were analysed post hoc. Cox regression, with myocardial infarction as a time-dependent covariate, was used to analyse time from randomisation to a composite of cardiovascular death or hospitalisation for heart failure.

Results: Patients who experienced myocardial infarction had a sevenfold higher risk of the composite endpoint (with myocardial infarction: n = 148, 25.0%; without myocardial infarction: n = 716, 8.2%; hazard ratio: 7.0; 95% confidence interval: 5.8, 8.4). The risk of the composite endpoint after myocardial infarction was not significantly lower in the liraglutide group ( n = 63, 23.0%) compared with placebo ( n = 85, 26.7%; hazard ratio: 0.91; 95% confidence interval: 0.66, 1.26).

Conclusion: The data demonstrated that having myocardial infarction significantly increased the risk of subsequent cardiovascular death or hospitalisation for heart failure. However, we did not find evidence for a reduced risk in these cardiovascular outcomes following myocardial infarction in patients treated with liraglutide versus placebo.

Keywords: Glucagon-like peptide-1 receptor agonists; cardiovascular death; cardiovascular outcomes; heart failure; myocardial infarction.

Conflict of interest statement

Declaration of conflicting interests: M.A.N. is on advisory boards or consulted for AstraZeneca, Boehringer Ingelheim, Eli Lilly & Co., Fractyl, GlaxoSmithKline, Menarini/Berlin-Chemie, Merck, Sharp & Dohme and Novo Nordisk; received grant support from Boehringer Ingelheim, Eli Lilly & Co., GlaxoSmithKline, Merck, Sharp & Dohme, Novartis Pharma and Novo Nordisk; served on the speakers’ bureau of AstraZeneca, Boehringer Ingelheim, Eli Lilly & Co., Menarini/Berlin-Chemie, Merck, Sharp & Dohme and Novo Nordisk. K.T., S.R. and M.B.T. are employees of and stockholders in Novo Nordisk. S.P.M. received consulting fees from Novo Nordisk and St Jude Medical and research support from Novo Nordisk, Terumo, The Medicines Company, AstraZeneca and Bristol Myers-Squibb.

Figures

Figure 1.

Risk of CV events (composite endpoint of CV death and hospitalisation for heart failure) among patients treated with liraglutide or placebo analysed by MI as a time-dependent dichotomous variable. *Although 292 patients in the liraglutide group and 339 patients in the placebo group experienced an MI during the trial, 274 and 319 patients, respectively, were included in this time-dependent analysis. This was because 18 and 20 patients were hospitalised for HF before the occurrence of MI in the liraglutide and placebo group, respectively. HR for first occurrence of hospitalisation for HF/CV death (FAS): 0.82 (95% CI: 0.72, 0.94; p = 0.005). †HR for CV death in the total population (FAS): 0.78 (95% CI: 0.66, 0.93; p = 0.007). ‡HR for hospitalisation for HF in the total population (FAS): 0.87 (95% CI: 0.73, 1.05; p = 0.14). CI: confidence interval; CV: cardiovascular; FAS: full analysis set; HF: heart failure; HR: hazard ratio of liraglutide/placebo; Lira: liraglutide; MI: myocardial infarction; Pbo: placebo.