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Event-Driven Intensification and Persistent Therapeutic Inertia in LDL-C Management Among 1,033,703 Patients With

Satoshi Shoji1, Peter Shrader2, Nikki L B Freeman2

  • 1Duke Clinical Research Institute, Durham, North Carolina, USA; Division of Cardiology and Department of Medicine, Duke University School of Medicine, Durham, North Carolina, USA; Department of Cardiology, Keio University School of Medicine, Tokyo, Japan.

JACC. Advances
|August 22, 2026
PubMed

Insights

Long-term control of low-density lipoprotein cholesterol (LDL-C) in atherosclerotic cardiovascular disease (ASCVD) patients shows an initial drop then plateau above target levels. Proactive monitoring and intervention are needed to reduce elevated LDL-C exposure.

Area of Science:

  • Cardiology
  • Public Health
  • Health Services Research

Background:

  • Long-term control of low-density lipoprotein cholesterol (LDL-C) is crucial for reducing atherosclerotic cardiovascular disease (ASCVD) risk.
  • Most large-scale evaluations of LDL-C management have been cross-sectional, limiting understanding of long-term trends.

Purpose of the Study:

  • To characterize long-term LDL-C trends in patients with established ASCVD.
  • To identify factors associated with achieving LDL-C goals (<70 mg/dL) and therapeutic intensification within one year.

Main Methods:

  • Utilized data from the cvMOBIUS-2 registry, pooling electronic health records from 17 U.S. health systems.
  • Included adults with ASCVD and baseline LDL-C ≥70 mg/dL, analyzing LDL-C trends using generalized estimating equations.
  • Employed multivariable logistic regression to identify factors associated with LDL-C goal attainment and therapeutic intensification.

Main Results:

  • Observed a "drop-and-plateau" pattern in LDL-C, stalling above 80 mg/dL despite follow-up.
  • Recurrent ASCVD events were strongly associated with achieving LDL-C goals and therapeutic intensification.
  • Peripheral artery disease was linked to lower odds of both LDL-C goal attainment and therapeutic intensification.

Conclusions:

  • LDL-C levels in ASCVD patients plateau significantly above guideline targets after an initial reduction.
  • Current lipid management is largely event-driven, highlighting a need for proactive, system-level strategies.
  • Timely interventions are essential to mitigate cumulative exposure to above-goal LDL-C levels.
Abstract

Keywords:
atherosclerotic cardiovascular diseaselipid-lowering therapylongitudinal trendlow-density lipoprotein cholesterolrecurrent eventtherapeutic inertia

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