Detailed Description of Myocardial Infarctions and the Various Subtypes in the LEADER Trial

Type 2 diabetes (T2D) is associated with increased risk of myocardial infarction (MI). In the LEADER trial (NCT01179048), liraglutide reduced the risk of a composite cardiovascular (CV) outcome (time to the first occurrence of CV death, non-fatal MI, or non-fatal stroke) versus placebo, both in addition to standard care. This result was driven by all components, but detailed characterization of the MIs has not been performed. The aim of this post hoc analysis was to characterize MIs in the trial, and within each treatment arm. A total of 9340 subjects, with T2D and established CV disease or high CV risk, were randomized 1:1 to receive liraglutide or placebo (both in addition to standard care) and followed for 3.5–5 years. Subjects experiencing MI were included in this analysis. A total of 780 MIs (first and recurrent) were observed: 359 with liraglutide and 421 with placebo (p=0.02). Of the MIs observed, 17.8% were silent. Numerically fewer fatal MIs were observed in the liraglutide arm compared with the placebo arm (Table). More liraglutide-versus placebo-treated subjects with MI had a history of coronary artery bypass graft (30.8% vs. 21.5%; p=0.008) and percutaneous coronary intervention (47.6% vs. 40.4%; p=0.070), while fewer had a history of left ventricular diastolic dysfunction (13.4% vs. 18.9%; p=0.061), peripheral arterial disease in the lower extremities (9.9% vs. 17.7%; p=0.005) and >50% stenosis of coronary, carotid or other arteries (33.2% vs. 41.0%; p=0.044) at baseline. Overall, 641 symptomatic MIs (555 non-ST-segment elevation MI [non-STEMI; 86.6%]) were observed: 297 with liraglutide and 344 with placebo. Among subjects who had a symptomatic MI and troponin information, a numerically lower proportion had troponin levels >5 times the upper reference limit (URL) in the liraglutide arm than in the placebo arm (Table). Fewer MIs and fatal MIs were observed in liraglutide-treated subjects than placebo-treated subjects. Symptomatic MIs in both arms were mainly non-STEMI. In subjects who had a symptomatic MI, there was a trend toward a lower proportion of subjects with troponin levels >5 times the URL with liraglutide versus placebo. Our results are suggestive of reduced infarct severity with liraglutide, which could impact the clinical prognosis of subjects experiencing MI.