Intensive LDL Cholesterol Targeting in Atherosclerotic Cardiovascular Disease

Key Takeaways

• The lower LDL target was associated with fewer primary composite cardiovascular events during 3 years of follow-up.
• Median LDL cholesterol during the trial was 56 mg/dL with intensive targeting and 66 mg/dL with conventional targeting.
• Prespecified safety end points were generally similar, with less creatinine elevation in the intensive-targeting group.

In patients with established atherosclerotic cardiovascular disease, lower LDL cholesterol targeting in the NEJM trial was associated with fewer composite cardiovascular events over a median 3.0 years of follow-up. Patients assigned to targets below 55 mg/dL and below 70 mg/dL had Kaplan–Meier estimated cumulative incidences of the primary endpoint of 6.6% and 9.7%, respectively. In this randomized secondary-prevention comparison, the lower target was associated with fewer events over follow-up.

This open-label superiority trial was conducted in South Korea and enrolled patients with atherosclerotic cardiovascular disease in secondary prevention. Investigators randomly assigned 3,048 patients in a 1:1 ratio to LDL cholesterol targets below 55 mg/dL or below 70 mg/dL. Group sizes were 1,526 in the intensive-targeting arm and 1,522 in the conventional-targeting arm after randomization. The primary endpoint combined cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, any revascularization, and hospitalization for unstable angina assessed at 3 years.

Over follow-up, the hazard ratio for the primary composite end point was 0.67, with a 95% confidence interval of 0.52 to 0.86. The P value for the between-group difference was 0.002. During the trial, median LDL cholesterol was lower in the intensive-targeting group than in the conventional-targeting group, consistent with the assigned targets. The lower hazard estimate aligned with the lower cumulative event burden seen in the intensive-targeting group across the prespecified 3-year assessment.

Prespecified safety endpoints were similar between groups, except for a lower incidence of creatinine elevation with intensive targeting during follow-up.

The authors concluded that targeting LDL cholesterol below 55 mg/dL was associated with a lower cardiovascular event risk at 3 years than targeting below 70 mg/dL in this population. The comparison was confined to a South Korean secondary-prevention population with established atherosclerotic cardiovascular disease.