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

Waqas A. Malick; Ori Waksman; Ron Do; Wolfgang Koenig; Aruna D. Pradhan; Erik S. G. Stroes; Robert S. Rosenson

doi:https://doi.org/10.1016/j.jacc.2023.02.034

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

Waqas A. Malick, Ori Waksman, Ron Do, Wolfgang Koenig, Aruna D. Pradhan, Erik S. G. Stroes, Robert S. Rosenson

Research output: Contribution to journal › Review article › Academic › peer-review

8 Citations (Scopus)

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.

Original language	English
Pages (from-to)	1646-1658
Number of pages	13
Journal	Journal of the American College of Cardiology
Volume	81
Issue number	16
DOIs	https://doi.org/10.1016/j.jacc.2023.02.034
Publication status	Published - 25 Apr 2023

Keywords

ANGPTL3
APOC3
VLDL
apolipoprotein-B
remnant cholesterol
triglycerides

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https://doi.org/10.1016/j.jacc.2023.02.034

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

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",

author = "Malick, {Waqas A.} and Ori Waksman and Ron Do and Wolfgang Koenig and Pradhan, {Aruna D.} and Stroes, {Erik S. G.} and Rosenson, {Robert S.}",

note = "Funding Information: The authors recognize the efforts of all of the physicians and faculty who participated in the Cardiovascular Clinical Trials Forum Atherosclerosis Sessions 2021 and made this paper possible. Publisher Copyright: {\textcopyright} 2023 American College of Cardiology Foundation",

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doi = "https://doi.org/10.1016/j.jacc.2023.02.034",

language = "English",

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AU - Malick, Waqas A.

AU - Waksman, Ori

AU - Do, Ron

AU - Koenig, Wolfgang

AU - Pradhan, Aruna D.

AU - Stroes, Erik S. G.

AU - Rosenson, Robert S.

N1 - Funding Information: The authors recognize the efforts of all of the physicians and faculty who participated in the Cardiovascular Clinical Trials Forum Atherosclerosis Sessions 2021 and made this paper possible. Publisher Copyright: © 2023 American College of Cardiology Foundation

PY - 2023/4/25

Y1 - 2023/4/25

N2 - 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.

AB - 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.

KW - ANGPTL3

KW - APOC3

KW - VLDL

KW - apolipoprotein-B

KW - remnant cholesterol

KW - triglycerides

UR - http://www.scopus.com/inward/record.url?scp=85152095495&partnerID=8YFLogxK

U2 - https://doi.org/10.1016/j.jacc.2023.02.034

DO - https://doi.org/10.1016/j.jacc.2023.02.034

M3 - Review article

C2 - 37076219

SN - 0735-1097

VL - 81

SP - 1646

EP - 1658

JO - Journal of the American College of Cardiology

JF - Journal of the American College of Cardiology

IS - 16

ER -

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

Abstract

Keywords

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