GLP-1 analog reduces major CV outcomes in patients with atherosclerotic poly-vascular disease
Effect of Liraglutide on Cardiovascular Events in Patients With Type 2 Diabetes Mellitus and Polyvascular Disease. Results of the LEADER Trial
Introduction and methods
In the LEADER (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results) trial, the GLP-1 analog liraglutide reduced CV events in patients with type 2 diabetes mellitus (T2DM) at high CV risk .
In this post hoc analysis of LEADER, the effects of liraglutide were assessed in patients with or without atherosclerotic poly-vascular disease in more than 1 vascular bed (coronary, cerebrovascular, and peripheral).
LEADER was a randomized trial of liraglutide (1.8 mg or maximum tolerated dose) versus placebo in 9,340 patients with T2DM and high CV risk (median follow-up: 3.8 years). The primary outcome was MACE, a composite of CV death, nonfatal myocardial infarction, or nonfatal stroke. The key secondary outcome (expanded MACE) also included hospitalization for unstable angina, coronary revascularization, or hospitalization for heart failure.
- Patients with poly-vascular disease had a higher risk of CV outcomes compared with those with single vascular disease (HR for MACE: 1.52; 95%CI: 1.33–1.73; HR for expanded MACE: 1.45; 95%CI: 1.31–1.62; HR for CV death: 1.41; 95%CI: 1.13–1.75).
- Liraglutide reduced MACE consistently in patients with poly-vascular disease (HR: 0.82; 95%CI: 0.66-1.02) and with single vascular disease (HR: 0.82; 95%CI: 0.71–0.95). Results were similar for expanded MACE and CV death.
- The risk reduction in MACE and expanded MACE in patients with single and poly-vascular disease was similar to that of the total trial population in LEADER.
- In patients without atherosclerotic CVD at baseline, the HR for liraglutide versus placebo for MACE was 1.08 (95%CI: 0.84–1.38), with similar results for expanded MACE and CV death.
- No significant interaction was found among risk groups, except for expanded MACE (P=0.03), This latter finding might be driven by the group of patients without atherosclerotic CVD.
In patients with T2DM and documented atherosclerotic CVD, the presence of poly-vascular disease was associated with a higher CV risk compared with single vascular disease patients. Liraglutide consistently reduced major CV outcomes in both groups.