Intensive LDL Cholesterol Targeting in Atherosclerotic Cardiovascular Disease
Clinical Snapshot
PICO Framework
| P — Population | Patients with established atherosclerotic cardiovascular disease in South Korea (n=3048) |
| I — Intervention | Intensive LDL cholesterol targeting (<55 mg/dL or <1.4 mmol/L) |
| C — Comparator | Conventional LDL cholesterol targeting (<70 mg/dL or <1.8 mmol/L) |
| O — Outcomes | Composite primary endpoint of cardiovascular death, nonfatal MI, nonfatal stroke, any revascularization, or hospitalization for unstable angina at 3 years |
Bottom Line
This large randomized trial provides robust evidence that targeting LDL cholesterol below 55 mg/dL (1.4 mmol/L) compared to below 70 mg/dL (1.8 mmol/L) significantly reduces cardiovascular events in patients with established atherosclerotic cardiovascular disease. The 33% relative risk reduction translates to preventing one major cardiovascular event for every 32 patients treated over 3 years, with similar safety profiles between groups. While the open-label design introduces some bias risk, the magnitude of benefit and statistical significance support intensive LDL targeting as standard care for secondary prevention. These findings reinforce current Australian guidelines recommending LDL targets below 1.4 mmol/L for very high-risk patients and support the use of intensive lipid-lowering therapy combinations when needed to achieve these targets.
Key Findings
P Value: P = 0.002
Effect Size: Hazard ratio 0.67 (33% relative risk reduction)
Primary Outcome: Composite cardiovascular events at 3 years: 6.6% (intensive) vs 9.7% (conventional)
Nnt Or Sensitivity: Number needed to treat = 32 (based on 3.1% absolute risk reduction)
Confidence Interval: 95% CI: 0.52 to 0.86
Clinical Application
Requires intensive lipid management and monitoring, achievable with current statin and adjunctive therapies Aligns with current Australian guidelines recommending LDL <1.4 mmol/L for very high-risk patients; PBS subsidizes appropriate lipid-lowering therapies including PCSK9 inhibitors for qualifying patients Patients with established atherosclerotic cardiovascular disease requiring secondary prevention
Abstract
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.).
References
- 1.Lee, Y. J., Lee, S. J., Kim, J. W., Lee, S. H., Kim, G. S., Park, J. H., Cho, J. M., Kang, W. C., Yoon, H. J., Kim, W. H., Lee, S. J., Lee, J. B., Jang, J. Y., Shin, S., Park, I. H., Kwon, S. U., Kim, S., Hong, S. J., Ahn, C. M., Kim, J. S., Ko, Y. G., Choi, D., Hong, M. K., Jang, Y., & Kim, B. K. (2026). Intensive LDL cholesterol targeting in atherosclerotic cardiovascular disease. New England Journal of Medicine. https://doi.org/10.1056/NEJMoa2600283
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