Aiming lower for LDL cholesterol cut cardiovascular events in a Korean trial

For patients who already have atherosclerotic heart disease, the guiding principle of cholesterol treatment has for years been "lower is better." The open question is how much lower is worth chasing. The Ez-PAVE trial tested one version of that question directly — aiming for an LDL cholesterol level below 55 milligrams per decilitre versus below 70 — and found the more aggressive target reduced cardiovascular events over three years [s1]. The result is encouraging, but two features of the trial mean it should be read with the caveats attached rather than as a settled verdict.

What the trial did

Ez-PAVE was an open-label superiority trial conducted in South Korea [s1]. Patients with established atherosclerotic cardiovascular disease were randomly assigned in a 1:1 ratio to one of two treatment targets: an LDL cholesterol level of less than 55 mg per decilitre (1.4 mmol per litre), the intensive-targeting group, or less than 70 mg per decilitre (1.8 mmol per litre), the conventional group [s1].

The primary endpoint was a composite of death from cardiovascular causes, non-fatal heart attack, non-fatal stroke, any revascularisation procedure, or hospitalisation for unstable angina, measured at three years [s1]. In all, 3,048 patients were randomised — 1,526 to the intensive target and 1,522 to the conventional one — and the median follow-up was 3.0 years [s1].

Two things about the design deserve flagging up front. The trial was open-label, meaning patients and their doctors knew which target each person was assigned to, which can influence other care decisions and the reporting of softer outcomes such as elective revascularisation [s1]. And it was funded in part by Yuhan, a pharmaceutical company, and registered as a study of ezetimibe combination therapy — one of the drug approaches used to drive LDL down [s1][s2]. Neither fact invalidates the result, but both belong in view when weighing it.

What it found

The targeting worked, and so, on this trial's reading, did the harder target. The median LDL cholesterol level achieved during the trial was 56 mg per decilitre (1.4 mmol per litre) in the intensive group and 66 mg per decilitre (1.7 mmol per litre) in the conventional group — a real separation between the two arms, though the intensive group landed slightly above its own sub-55 aim [s1].

A primary-endpoint event occurred in 100 patients in the intensive group and 147 in the conventional group, corresponding to Kaplan-Meier cumulative incidences of 6.6% and 9.7% (hazard ratio 0.67; 95% confidence interval 0.52 to 0.86; P = 0.002) [s1]. That is a relative reduction of about a third and an absolute gap of roughly three percentage points over three years [s1].

On safety, the incidence of prespecified safety endpoints was similar between the two groups, with one exception that ran in the intensive group's favour: a lower incidence of creatinine elevation, a marker sometimes watched in patients on intensive lipid-lowering [s1]. The abstract reports no offsetting safety penalty for aiming lower [s1].

How to read it

The authors conclude that, among patients with atherosclerotic cardiovascular disease, targeting an LDL level below 55 mg per decilitre "resulted in a lower risk of cardiovascular events at 3 years than targeting a level of less than 70" [s1]. That aligns with the broad direction of cholesterol science and with existing guidelines that already endorse a sub-55 goal for the highest-risk patients.

The reasons for caution are specific rather than general. The composite endpoint includes revascularisation and unstable-angina hospitalisation — outcomes more open to the influence of an open-label design than death or heart attack are — so an unblinded trial carries a built-in risk of inflating exactly this kind of result [s1]. And the industry funding, while disclosed, means independent replication would strengthen confidence [s1]. The finding is best read as consistent with, and supportive of, a lower target rather than as decisive new proof.

For readers, the practical translation is modest: this trial adds weight to the case that, for people who already have heart disease, pushing LDL well below 70 can pay off — a decision for a patient and their doctor, not a number to chase alone. Related coverage has examined what cholesterol numbers actually mean, an oral PCSK9 inhibitor tested head-to-head, and inclisiran and bempedoic acid for lowering LDL.

What to watch

The questions ahead are whether an independent, blinded trial reproduces the benefit, whether it holds across populations beyond South Korea, and how the harder target performs on the hardest endpoints — death and heart attack — rather than the composite as a whole [s1].

This article describes trial results and is not medical advice. Decisions about cholesterol treatment should be made with a clinician.

Sources

• Intensive LDL Cholesterol Targeting in Atherosclerotic Cardiovascular Disease — New England Journal of Medicine, 28 March 2026
• Ez-PAVE trial record, NCT04626973 — ClinicalTrials.gov