EvidenceAlerts

Lee YJ, Lee SJ, Kim JW, et al. Intensive LDL Cholesterol Targeting in Atherosclerotic Cardiovascular Disease. N Engl J Med. 2026 Mar 28. doi: 10.1056/NEJMoa2600283. (Original study)
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.).

Ratings
Discipline Area Score
Family Medicine (FM)/General Practice (GP) 6 / 7
General Internal Medicine-Primary Care(US) 6 / 7
Internal Medicine 6 / 7
Cardiology Coming Soon...
Comments from MORE raters

General Internal Medicine-Primary Care(US) rater

Lower LDL is better.

General Internal Medicine-Primary Care(US) rater

I am sure this study will accelerate the race to the bottom, "how low can you go?" The only worry I have is that something with proven benefit in a higher risk population will become favored by people of normal risk in their attempt to avoid becoming someone at higher risk. This is what happened in low-dose aspirin therapy. What I fear is a bunch of average-risk people out there getting PCSK/9 drugs because they think this will improve their heart outcomes.

Internal Medicine rater

Cholesterol management is extremely important for Internal Medicine providers. This study providers good data indicating therapeutic goals may need to change.
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