Intensive LDL-C Targeting in ASCVD
Intensive vs Conventional LDL-C Targeting in Patients With Atherosclerotic Cardiovascular Disease (Ez-PAVE)
Presented by Byeoung-Keuk Kim — Severance Cardiovascular Hospital, Yonsei University
Subspecialty: Lipid / Prevention
Published in NEJM
Key Result
Targeting LDL-C <55 mg/dL vs <70 mg/dL reduced major CV events by 33% at 3 years (6.6% vs 9.7%) in ASCVD patients. CV death/MI/stroke was also significantly lower (2.3% vs 3.6%). First randomized head-to-head comparison of LDL-C targets.
What did this trial find?
The Ez-PAVE trial, the first randomized head-to-head comparison of two LDL-C targets in ASCVD patients, found that targeting LDL-C <55 mg/dL vs <70 mg/dL reduced major cardiovascular events by 33% at 3 years (6.6% vs 9.7%), with a similar safety profile. Published simultaneously in NEJM and presented at ACC.26, the trial provides direct randomized evidence supporting the more aggressive LDL-C target already recommended in updated guidelines. Reaction has been largely supportive, with prominent lipidologists calling for simplification of guidelines and noting the results complement IMPROVE-IT and reinforce the "lower is better" paradigm, though some note limitations including the all-East-Asian population and the 39% who did not reach the intensive target.
Why does this trial matter?
Mostly straightforward and supportive coverage. The trial results align with existing guideline recommendations and prior observational/trial evidence (IMPROVE-IT). The main points of debate are practical—whether guidelines should simplify to a single secondary prevention LDL target rather than maintaining high-risk/very-high-risk tiers, the generalizability beyond an East Asian population, and the 39% who did not achieve the intensive target. There is no fundamental controversy about the findings themselves.
Study Design
Randomized, open-label, controlled trial across 17 sites in South Korea
Clinical Implications
Provides the first direct randomized evidence that targeting LDL-C to <55 mg/dL leads to significantly fewer major cardiovascular events than the conventional <70 mg/dL target in ASCVD patients, without compromising safety. Firms the foundation of current lipid guidelines in secondary prevention.
Abstract
The Ez-PAVE trial was the first randomized, head-to-head comparison of two LDL-C targets in patients with atherosclerotic cardiovascular disease (ASCVD). Conducted from January 2021 through July 2022 at 17 sites in South Korea, the trial enrolled 3,048 patients: 1,526 assigned to an intensive target of <55 mg/dL and 1,522 to a conventional target of <70 mg/dL. The mean age was 64 years and 21% were women. At 3 years, median LDL-C was 56 mg/dL in the intensive group vs 66 mg/dL in the conventional group. Treatment decisions were at clinician discretion using high-intensity statins, ezetimibe, and PCSK9 inhibitors as needed. The primary composite endpoint (CV death, nonfatal MI, nonfatal stroke, any revascularization, or hospitalization for unstable angina) occurred in 6.6% of the intensive group vs 9.7% of the conventional group — a 33% risk reduction. The composite of CV death, MI, or stroke was also significantly lower (2.3% vs 3.6%). The safety profile was similar across groups. 39% of intensive group patients did not reach the <55 mg/dL target.