Clinical significance of low-density lipoprotein cholesterol percentage reduction and attained levels after percutaneous coronary intervention.

Background: Differences exist between European and American guideline recommendations regarding targets for low-density lipoprotein cholesterol (LDL-C) levels after percutaneous coronary intervention (PCI), with European guidance advocating for more aggressive reduction to less than 1.4 mmol/L compared with the American guideline, which recommends an LDL-C level of 1.8 mmol/L or greater as the threshold for treatment intensification. We aimed to evaluate clinical outcomes according to percentage reduction of LDL-C levels and to compare the outcomes according to the attained LDL-C levels after PCI.

Methods: This nationwide cohort study included adults in South Korea who underwent PCI and health screening within 3 years before and after PCI. Participants were divided into groups with a reduction of LDL-C levels of less than 50% and of 50% or greater. The group with LDL-C reduction of 50% or greater was stratified into categories of LDL-C level after PCI: less than 1.4 mmol/L, 1.4 to less than 1.8 mmol/L, and 1.8 mmol/L or greater. The primary end point was major adverse cardiac and cerebrovascular events (MACCE), defined as a composite of cardiovascular death, spontaneous myocardial infarction (MI), repeat revascularization, and ischemic stroke.

Results: We included 135 877 adult participants. A total of 40.1% achieved a reduction of LDL-C levels of 50% or greater ( = 54 551). During a median follow-up of 7.4 years, the group with a reduction of 50% or greater had a multivariable-adjusted hazard ratio (HR) for MACCE of 0.78 (95% confidence interval [CI] 0.76-0.80). Among patients who achieved a reduction of LDL-C levels of 50% or greater, the multivariable-adjusted HR for MACCE was 1.07 (95% CI 1.02-1.13) for the group with LDL-C levels of 1.4 to less than 1.8 mmol/L after PCI and 1.12 (95% CI 1.04-1.21) for the group with levels of greater than 1.8 mmol/L. The risk of spontaneous MI was also higher in the group with LDL-C levels of 1.8 mmol/L or greater than in the group with levels of less than 1.4 mmol/L (HR 1.36, 95% CI 1.14-1.62).

Interpretation: Among patients who underwent PCI, those who achieved a reduction in LDL-C levels of 50% or greater had a reduced risk of MACCE, regardless of baseline LDL-C levels. Among patients with a reduction in LDL-C levels of 50% or greater, compared with patients with an LDL-C level less than 1.4 mmol/L after PCI, those with an LDL-C level of greater than 1.8 mmol/L and a level of 1.4 to less than 1.8 mmol/L had an increased risk of MACCE. These findings suggest that while achieving an LDL-C reduction of 50% or greater remains a critical therapeutic goal, targeting LDL-C levels of less than 1.4 mmol/L after PCI may provide additional clinical benefit.

Trial Registration: ClinicalTrials.gov, NCT06338956.