Christie Ballantyne
Guidelines questionCardiologist, Baylor College of MedicineGuidelines should drop the high-risk vs. very-high-risk split and simplify to one secondary prevention category
Original post ↗What happened
Targeting LDL-C <55 mg/dL reduces 3-year cardiovascular events vs <70 mg/dL in ASCVD patients.
Guidelines should drop the high-risk vs. very-high-risk split and simplify to one secondary prevention category
Christie Ballantyne · Original post ↗
Ballantyne argues that Ez-PAVE showed benefit across secondary prevention patients who were not classified as very high risk, which undermines the case for maintaining two risk tiers. He suggests collapsing them into a single secondary prevention category would make guidance far simpler for primary care physicians.
Experts uniformly read Ez-PAVE as the first randomized proof that targeting LDL-C below 55 mg/dL beats the 70 mg/dL threshold in secondary prevention, and several say 55 should now be the standard goal.
The reaction is one-sided: every commenting clinician treats Ez-PAVE as confirmatory evidence that a lower LDL-C target improves outcomes in patients with established cardiovascular disease, and none raises major objections to the findings. Several voices call for simplifying guidelines around the 55 mg/dL target. The live question is whether these results, drawn from a Korean cohort using oral therapies, will prompt guideline bodies worldwide to collapse risk tiers and adopt a single, more intensive target for all secondary prevention patients.
Multiple experts agree that Ez-PAVE provides the randomized evidence needed to support 55 mg/dL as the LDL-C goal in secondary prevention, describing the result as both clinically meaningful and consistent with prior data.
Whether guideline committees will use these data to eliminate the distinction between high-risk and very-high-risk secondary prevention categories remains to be seen.
Experts also note the need for definitive trials testing intensive LDL-C targets in primary prevention populations and with other treatment combinations.
Christie Ballantyne
Guidelines questionCardiologist, Baylor College of MedicineGuidelines should drop the high-risk vs. very-high-risk split and simplify to one secondary prevention category
Original post ↗Christopher Cannon
Practice takeCardiologist, Brigham and Women's Hospital55 mg/dL is the new goal and clinicians need to work hard to get patients there
Original post ↗Karen Aspry
ContextPreventive cardiologist, Brown University HealthResults are consistent with what IMPROVE-IT and European observational data already showed
Original post ↗Jeffrey L. Probstfield
Results readoutProfessor of medicine, University of WashingtonEz-PAVE firms the guideline foundation and opens the door for trials in primary prevention
Original post ↗Byeong-Keuk Kim
Results readoutInterventional cardiologist, Severance Hospital, Yonsei UniversityBenefits of targeting below 55 mg/dL were consistent across subgroups with no safety concerns
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Why the trial, key points, 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?
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Expert reaction
NEJM · ACC Annual Scientific Session 2025
1 expert quoted, 0 with a clear stance so far. We show the split once 3 have one.
Expert labels are toward Intensive LDL-C Targeting in ASCVD's result, from named public quotes (n=0). As of Sep 5, 2026.
Experts uniformly read Ez-PAVE as the first randomized proof that targeting LDL-C below 55 mg/dL beats the 70 mg/dL threshold in secondary prevention, and several say 55 should now be the standard goal.
The reaction is one-sided: every commenting clinician treats Ez-PAVE as confirmatory evidence that a lower LDL-C target improves outcomes in patients with established cardiovascular disease, and none raises major objections to the findings. Several voices call for simplifying guidelines around the 55 mg/dL target. The live question is whether these results, drawn from a Korean cohort using oral therapies, will prompt guideline bodies worldwide to collapse risk tiers and adopt a single, more intensive target for all secondary prevention patients.
Multiple experts agree that Ez-PAVE provides the randomized evidence needed to support 55 mg/dL as the LDL-C goal in secondary prevention, describing the result as both clinically meaningful and consistent with prior data.
Whether guideline committees will use these data to eliminate the distinction between high-risk and very-high-risk secondary prevention categories remains to be seen. Experts also note the need for definitive trials testing intensive LDL-C targets in primary prevention populations and with other treatment combinations.
“This is really saying that 55 is our new goal and we need to really embrace that and work hard to get patients to that goal.”
Ballantyne argues that Ez-PAVE showed benefit across secondary prevention patients who were not classified as very high risk, which undermines the case for maintaining two risk tiers. He suggests collapsing them into a single secondary prevention category would make guidance far simpler for primary care physicians.
Cannon frames the result as settling the target debate, saying 55 mg/dL should now be embraced as the standard and that the clinical community must commit to reaching it in practice.
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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