What happened
Targeting LDL-C <55 mg/dL reduces 3-year cardiovascular events vs <70 mg/dL in ASCVD patients.
“These findings provide the randomized evidence for more intensively lowering LDL strategy for secondary prevention consistent with the current guideline recommendations.”
Byeong-Keuk Kim, MD ↗Christie Ballantyne
Guidelines questionCardiologist, Baylor College of Medicine“Why do we have to have two categories: high risk and very high risk? This study just took secondary prevention—they weren't very high risk—and you got the benefits there. It seems to me we would make it a lot simpler [for] primary care physicians [if we] just have one category—secondary prevention.”
Ballantyne points out that the trial enrolled secondary prevention patients who were not very high risk, and they still benefited. He argues one secondary prevention category would make things much simpler for primary care physicians.
Karen Aspry
ContextPreventive cardiologist, Brown University Health“The results of Ez-PAVE are not that surprising given that we know from IMPROVE-IT and also some observational data from Europe showing that dual oral therapy post-ACS targeting LDL down to 55 achieves better outcomes.”
Aspry says the results fit what IMPROVE-IT and observational data from Europe already showed: dual oral therapy after ACS that targets LDL down to 55 achieves better outcomes.
“The Ez-PAVE trial firms the foundation of lipid guidelines in secondary prevention and potentially paves the way for more definitive trials to evaluate targeted LDL-C levels in other populations, with other treatment combinations, and with other LDL-C goals for primary prevention.”
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Why the trial, tables, limitations, PICO, abstract, media & sources
Why the trial?
The trial was conducted to compare the cardiovascular event risk between targeting an LDL cholesterol level of less than 55 mg/dL versus less than 70 mg/dL in patients with atherosclerotic cardiovascular disease.
Does targeting an LDL cholesterol level of less than 55 mg/dL reduce cardiovascular events in patients with atherosclerotic cardiovascular disease compared to targeting less than 70 mg/dL?
RCT (n=3,048)
Open-label
1:1
Does targeting an LDL cholesterol level of less than 55 mg/dL reduce cardiovascular events in patients with atherosclerotic cardiovascular disease compared to targeting less than 70 mg/dL?
Experts read this trial as solid confirmation that patients with established cardiovascular disease do better with a lower cholesterol goal, a finding that fits prior evidence rather than overturning it.
The few voices so far accept the result and see the benefit of the stricter target as applying broadly to patients already living with cardiovascular disease. One expert calls it unsurprising given earlier trial and observational data. The live question is whether guidelines should drop the split between high-risk and very-high-risk patients and use one simpler secondary prevention target.
Two clinicians agree the benefit of the lower target is not limited to a narrow, highest-risk subset. They read it as applying broadly to secondary prevention patients.
Ballantyne asks whether the high-risk and very-high-risk categories are still needed when an unselected secondary prevention population benefited. It is not yet clear whether guidelines will collapse them into one category.
In patients with atherosclerotic cardiovascular disease, an intensive LDL cholesterol target of <55 mg/dL significantly reduced the composite risk of cardiovascular events over 3 years compared to a conventional target of <70 mg/dL.
BACKGROUND: Despite guideline recommendations, evidence from randomized trials evaluating the appropriate low-density lipoprotein (LDL) cholesterol target for secondary prevention in patients with atherosclerotic cardiovascular disease remains limited. METHODS: In this open-label superiority trial conducted in South Korea, we randomly assigned patients with atherosclerotic cardiovascular disease in a 1:1 ratio to a target LDL cholesterol level of less than 55 mg per deciliter (1.4 mmol per liter) (intensive-targeting group) or less than 70 mg per deciliter (1.8 mmol per liter) (conventional-targeting group). The primary end point was a composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, any revascularization, or hospitalization for unstable angina at 3 years. Safety was also assessed. RESULTS: Of 3048 patients who underwent randomization, 1526 were assigned to the intensive-targeting group and 1522 to the conventional-targeting group. The median follow-up was 3.0 years. The median LDL cholesterol level during the trial was 56 mg per deciliter (1.4 mmol per liter) in the intensive-targeting group and 66 mg per deciliter (1.7 mmol per liter) in the conventional-targeting group. A primary end-point event occurred in 100 patients (Kaplan-Meier estimate of cumulative incidence, 6.6%) in the intensive-targeting group and in 147 patients (Kaplan-Meier estimate of cumulative incidence, 9.7%) in the conventional-targeting group (hazard ratio, 0.67; 95% confidence interval, 0.52 to 0.86; P = 0.002). The incidence of prespecified safety end points was similar in the two trial groups, except for a lower incidence of creatinine elevation in the intensive-targeting group. CONCLUSIONS: Among patients with atherosclerotic cardiovascular disease, targeting an LDL cholesterol level of less than 55 mg per deciliter resulted in a lower risk of cardiovascular events at 3 years than targeting a level of less than 70 mg per deciliter. (Funded by the Cardiovascular Research Center and Yuhan; Ez-PAVE ClinicalTrials.gov number, NCT04626973.).
Lee et al. (2026) conducted an RCT in Atherosclerotic cardiovascular disease (n=3,048). Intensive LDL cholesterol targeting vs. Conventional targeting (Target <70 mg/dL [1.8 mmol/L]) was evaluated on Composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, any revascularization, or hospitalization for unstable angina at 3 years (HR 0.67, 95% CI 0.52-0.86, p=0.002). Intensive LDL cholesterol targeting (<55 mg/dL) reduced the risk of cardiovascular events compared to conventional targeting (<70 mg/dL) (HR 0.67; 95% CI 0.52-0.86; P=0.002).
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