Clinical Outcomes of Ezetimibe Plus Statins in Patients With Lower Extremity Artery Disease

The beneficial outcomes of ezetimibe plus statin therapy are well-established in coronary artery disease, but these remain unknown in lower extremity artery disease (LEAD).

This study evaluated the efficacy of an intensified lipid-lowering strategy involving ezetimibe plus statins vs statin monotherapy for reducing major adverse limb events and mortality in patients with LEAD.

This retrospective analysis included patients aged ≥18 years diagnosed with LEAD from the TriNetX global health care database from 2013 to 2022, excluding those with recent acute coronary syndrome or stroke. The primary outcome was the 12-month cumulative incidence of major lower limb amputation and all-cause death as a composite endpoint. Propensity score matching was used to adjust for baseline characteristics and confounders, yielding 4,204 patients in each group.

The composite endpoint was lower with statins plus ezetimibe vs statin monotherapy (5.8% vs 10.2%; P < 0.001; HR: 0.54; 95% CI: 0.46-0.64). Taken individually, both major lower limb amputation (2.7% vs 4.6%; P < 0.001; HR: 0.57; 95% CI: 0.45-0.72) and all-cause death (3.4% vs 6.3%; P < 0.001; HR: 0.52; 95% CI: 0.42-0.65) were significantly lower with combination therapy. Subgroup analyses showed consistent effects across all subgroups.

Compared to statin monotherapy, an intensified lipid-lowering strategy (ie, ezetimibe plus statins), significantly reduced the incidence of major lower limb amputation and all-cause mortality in real-world patients with LEAD.