BACKGROUND: The relationships among low-density lipid cholesterol (LDL-C) levels, statin use and cardiovascular (CV) outcomes are well established. In the LEADER trial, the human glucagon-like peptide 1 analogue liraglutide reduced CV events in patients with type 2 diabetes (T2D) at high CV risk.
PURPOSE: This post hoc analysis evaluated liraglutide effects on CV outcomes by baseline LDL-C and statin use.
METHODS: LEADER (NCT01179048) studied liraglutide (1.8 mg or maximum tolerated dose) vs placebo, both in addition to standard care, in 9340 patients with T2D and high CV risk (median follow-up 3.8 years). Primary outcome: composite of CV death, non-fatal myocardial infarction, or non-fatal stroke (major adverse CV events, MACE). The key secondary expanded outcome (expanded MACE) also included hospitalisation for unstable angina or heart failure, or revascularisation. Cox regression evaluated the liraglutide effect on CV outcomes by baseline LDL-C <1.3 mmol/L, 1.3–1.8 mmol/L and >1.8 mmol/L, and statin use at baseline.
RESULTS: In LEADER, 9187 patients had LDL-C measured: 926 (10.1%), 2021 (22.0%) and 6240 (67.9%) had baseline LDL-C <1.3 mmol/L, 1.3–1.8 mmol/L or >1.8 mmol/L, respectively. Baseline characteristics: see Table. Within the groups by LDL-C level, baseline characteristics were well-balanced across treatment groups. Liraglutide consistently reduced MACE vs placebo irrespective of baseline LDL-C (hazard ratio [HR] 0.75, 95% CI 0.51–1.11 vs HR 0.81, 95% CI 0.64–1.02 vs HR 0.90, 95% CI 0.79–1.03, p interaction=0.57). Results were similar for expanded MACE and individual MACE components (Figure). Liraglutide reduced MACE vs placebo in statin users (72%) (HR 0.83, 95% 0.73–0.94). Non-statin users (28%): HR 0.97, 95% CI 0.79–1.20 (interaction between statin and non-statin users p=0.19). Results were similar in a model adjusted for baseline characteristics.
CONCLUSIONS: In LEADER, liraglutide was associated with lower risk of major CV events in patients with T2D across the entire spectrum of LDL-C and statin use, with event reduction even in patients with the lowest LDL-C levels.