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Review
. 2023 Jun 6;12(11):e028892.
doi: 10.1161/JAHA.122.028892. Epub 2023 Jun 1.

Evolving Management of Low-Density Lipoprotein Cholesterol: A Personalized Approach to Preventing Atherosclerotic Cardiovascular Disease Across the Risk Continuum

Michael J Wilkinson  1 , Norman E Lepor  2   3 , Erin D Michos  4
Affiliations
Review

Evolving Management of Low-Density Lipoprotein Cholesterol: A Personalized Approach to Preventing Atherosclerotic Cardiovascular Disease Across the Risk Continuum

Michael J Wilkinson et al. J Am Heart Assoc. .

Abstract

Management of elevated low-density lipoprotein cholesterol (LDL-C) is central to preventing atherosclerotic cardiovascular disease (ASCVD) and key to reducing the risk of ASCVD events. Current guidelines on the management of blood cholesterol recommend statins as first-line therapy for LDL-C reduction according to an individual's ASCVD risk and baseline LDL-C levels. The addition of nonstatin lipid-lowering therapy to statins to achieve intensive LDL-C lowering is recommended for patients at very high risk of ASCVD events, including patients with familial hypercholesterolemia who have not achieved adequate LDL-C lowering with statins alone. Despite guideline recommendations and clinical trial evidence to support the use of lipid-lowering therapies for ASCVD risk reduction, most patients at high or very high risk do not meet LDL-C thresholds. This review explores the challenges associated with LDL-C lowering in contemporary clinical practice and proposes a framework for rethinking the binary definition of ASCVD, shifting from "primary" versus "secondary" prevention to a "continuum of risk." The approach considers the role of plaque burden and progression in subclinical disease and emphasizes the importance of early risk assessment and treatment for preventing first cardiovascular events. Patients at high risk of ASCVD events who require significant LDL-C lowering should be considered for combination therapies comprising statin and nonstatin agents. Practical guidance for the pharmacological management of elevated LDL-C, both now and in the future, is provided.

Keywords: atherosclerosis; atherosclerotic cardiovascular disease; lipids; low‐density lipoprotein cholesterol; prevention.

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Figures

Figure 1
Figure 1. Challenges to low‐density lipoprotein cholesterol (LDL‐C) management in patients with, and at risk for, atherosclerotic cardiovascular disease (ASCVD).
Figure 2
Figure 2. Risk factors and progression along the continuum of atherosclerotic cardiovascular disease (ASCVD)., , ,
ABI indicates ankle‐brachial index; apoB, apolipoprotein B; CKD, chronic kidney disease; hs‐CRP, high‐sensitivity C‐reactive protein; Lp(a), lipoprotein(a); MI, myocardial infarction; and PAD, peripheral arterial disease.
Figure 3
Figure 3. Practical points: bempedoic acid and inclisiran., , , , , , ,
ASCVD indicates atherosclerotic cardiovascular disease; CLEAR, Cholesterol Lowering via Bempedoic Acid, an ACL [ATP‐Citrate Lyase]‐Inhibiting Regimen; DDI, drug––drug interaction; HCP, health care professional; hs‐CRP, high‐sensitivity C‐reactive protein; Lp(a), lipoprotein(a); MACE, major adverse cardiovascular events; and SC, subcutaneous.
Figure 4
Figure 4. The continuum of atherosclerotic cardiovascular disease (ASCVD) risk.
Management of low‐density lipoprotein cholesterol (LDL‐C) levels across the continuum of ASCVD risk to prevent first and subsequent cardiovascular events. PCSK9 indicates proprotein convertase subtilisin/kexin type 9.
See this image and copyright information in PMC

References

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