Ez-PAVE: Lower Cholesterol Target Outperforms Historic Target in ASCVD

The Ez-PAVE trial, presented at ACC 2026 and simultaneously published in the New England Journal of Medicine, fills a critical evidentiary gap in lipid management. Prior LDL targets were largely derived from the achieved cholesterol levels in drug-versus-placebo trials rather than from trials that directly compared specific treatment targets. Ez-PAVE changes that: it is the first randomized trial to directly pit an LDL target of below 55 mg/dL against one of below 70 mg/dL in patients with established ASCVD.

Patients in the intensive arm achieved a median LDL of 56 mg/dL versus 66 mg/dL in the conventional arm—a difference of roughly 10 mg/dL. That seemingly modest gap translated to a 3.1% absolute risk reduction and a 33% relative risk reduction in major cardiovascular events over just 3 years. The finding is particularly striking given how close the groups were in absolute LDL levels; both technically achieved sub-70 mg/dL results, yet the difference in outcomes was substantial.

This has direct implications for clinical practice. In the US, the GOLD registry has shown that two-thirds of patients with ASCVD have LDL levels above 70 mg/dL, and therapy is rarely intensified even when patients fall short of goals. Ez-PAVE challenges the "close enough" mentality: a baseline median LDL of 75 mg/dL—which might appear satisfactory to many clinicians—was insufficient for optimal risk reduction. The trial confirms that guideline-recommended targets below 55 mg/dL are not arbitrary; they correspond to clinically meaningful reductions in hard events. For primary care providers managing the bulk of secondary prevention patients, Ez-PAVE is a call to close the gap between where LDL is and where it needs to be.