Clinical Trial Design for Triglyceride-Rich Lipoprotein-Lowering Therapies: JACC Focus Seminar 3/3

J Am Coll Cardiol. 2023 Apr 25;81(16):1646-1658. doi: 10.1016/j.jacc.2023.02.034.

Abstract

Triglyceride-rich lipoproteins (TRLs) are a source of residual risk in patients with atherosclerotic cardiovascular disease, and are indirectly correlated with triglyceride (TG) levels. Previous clinical trials studying TG-lowering therapies have either failed to reduce major adverse cardiovascular events or shown no linkage of TG reduction with event reduction, particularly when these agents were tested on a background of statin therapy. Limitations in trial design may explain this lack of efficacy. With the advent of new RNA-silencing therapies in the TG metabolism pathway, there is renewed focus on reducing TRLs for major adverse cardiovascular event reduction. In this context, the pathophysiology of TRLs, pharmacological effects of TRL-lowering therapies, and optimal design of cardiovascular outcomes trials are major considerations.

Keywords: ANGPTL3; APOC3; VLDL; apolipoprotein-B; remnant cholesterol; triglycerides.

Publication types

  • Review
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Atherosclerosis* / drug therapy
  • Cardiovascular Diseases* / prevention & control
  • Clinical Trials as Topic
  • Humans
  • Lipoproteins / metabolism
  • Triglycerides / metabolism

Substances

  • Lipoproteins
  • Triglycerides