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The Legacy Effect in Treating Hypercholesterolemia

John B Kostis1, Mrinali Shetty1, Yuvraj Singh Chowdhury1

  • 1Rutgers Robert Wood Johnson Medical School, Cardiovascular Institute, New Brunswick, NJ, USA.

Journal of Cardiovascular Pharmacology and Therapeutics
|February 29, 2020
PubMed

Insights

Early treatment for hypercholesterolemia, a lifelong condition, shows lasting benefits. The legacy effect in clinical trials demonstrates that interventions provide long-term advantages, reducing cardiovascular events.

Area of Science:

  • Cardiology
  • Clinical Pharmacology
  • Epidemiology

Background:

  • Hypercholesterolemia and atherosclerotic cardiovascular disease (ASCVD) risk factors are lifelong conditions.
  • Randomized controlled trials (RCTs) typically last 3-5 years, potentially underestimating long-term treatment effects.

Purpose of the Study:

  • To summarize evidence for the legacy effect in hypercholesterolemia treatment.
  • To describe potential mechanisms underlying the legacy effect.
  • To discuss the clinical relevance of the legacy effect for patient care.

Main Methods:

  • Systematic review of 13 published randomized clinical trials.
  • Analysis focused on lipid-lowering agents compared to placebo or usual care.
  • Evaluation of trial data for a legacy effect post-randomized phase.

Main Results:

  • A legacy effect was demonstrated in all reviewed studies.
  • Current guidelines recommend high-intensity statins for manifest ASCVD and individualized primary prevention.
  • The legacy effect implies significant long-term clinical benefits.

Conclusions:

  • The legacy effect leads to substantial long-term clinical benefits, including prevention of fatal and nonfatal cardiovascular events.
  • Initiating lipid-lowering therapy early is associated with reduced event rates.
  • Long-term follow-up in clinical trial design is crucial for evaluating legacy effects.
Abstract

Keywords:
PCSK9clinical trialshypercholesterolemialegacy effectniacinstatins

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