Therapy targeting lower LDL-C levels improves cardiovascular outcomes

Targeting low-density lipoprotein cholesterol (LDL-C) levels <55 mg/dL is associated with improved cardiovascular outcomes compared with a target of <70 mg/dL in patients with atherosclerotic cardiovascular disease, without an increase in adverse events, according to a report by Prof. Byeong-Keuk Kim (Yonsei University College of Medicine, Republic of Korea) [1].

Ez-PAVE (NCT04626973) was a phase 3, randomised, investigator-led trial conducted entirely in Korea. Patients with atherosclerotic cardiovascular disease were assigned to either an intensive LDL-C target (<55 mg/dL) or a conventional target (<70 mg/dL). Within these groups, patients were further randomised to receive either a statin plus ezetimibe combination or a statin monotherapy. The primary endpoint was a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, any revascularisation, or hospitalisation for unstable angina. In total, 3,048 patients were randomised and included.

In Ez-PAVE, intensive LDL-C targeting resulted in significantly lower rates of the primary endpoint compared with conventional targeting, corresponding to a 33% reduction in relative risk. Analyses of individual components showed no significant differences in cardiovascular death or all-cause mortality, but significantly lower rates of non-fatal myocardial infarction, non-fatal stroke, and revascularisation with intensive targeting. Safety analyses demonstrated no significant differences between groups in new-onset diabetes, worsening of glycaemic control, statin-associated muscle symptoms, new cancer diagnoses, or elevations in aminotransferases or creatine kinase. Notably, intensive targeting was associated with significantly lower rates of creatinine elevation to >1.5 times baseline.

“Ez-PAVE is the first randomised trial comparing LDL-C targets of <55 mg/dL versus <70mg/dL in patients with atherosclerotic cardiovascular disease,” concluded Prof. Kim. “Intensive targeting was associated with a significantly lower 3-year risk of the composite endpoint than conventional targeting, without major safety concerns. These findings provide randomised evidence supporting more intensive lipid-lowering strategies for secondary prevention, consistent with guideline recommendations.”

Kim K, et al. Intensive low-density lipoprotein cholesterol targeting in patients with atherosclerotic cardiovascular disease. ACC 2026, 28–30 March, New Orleans, LA, USA.