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Cited by 26Lipid metabolism and disordersLipoproteins and Cardiovascular HealthDiabetes, Cardiovascular Risks, and Lipoproteins

New approaches to triglyceride reduction: is there any hope left?

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Filtz, Annalisa, Parihar, Siddhant, Greenberg, Garred S., Park, Christine M., Scotti, Andrea, Lorenzatti, Daniel, Badimon, Juan J, Soffer, Daniel E. +5 more·2024·American Journal of Preventive Cardiology
DOI 10.1016/j.ajpc.2024.100648PMC PMC10998004
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Abstract

Triglycerides play a crucial role in the efficient storage of energy in the body. Mild and moderate hypertriglyceridemia (HTG) is a heterogeneous disorder with significant association with atherosclerotic cardiovascular disease (ASCVD), including myocardial infarction, ischemic stroke, and peripheral artery disease and represents an important component of the residual ASCVD risk in statin treated patients despite optimal low-density lipoprotein cholesterol reduction. Individuals with severe HTG (>1,000 mg/dL) rarely develop atherosclerosis but have an incremental incidence of acute pancreatitis with significant morbidity and mortality. HTG can occur from a combination of genetic (both mono and polygenic) and environmental factors including poor diet, low physical activity, obesity, medications, and diseases like insulin resistance and other endocrine pathologies. HTG represents a potential target for ASCVD risk and pancreatitis risk reduction, however data on ASCVD reduction by treating HTG is still lacking and HTG-associated acute pancreatitis occurs too rarely to effectively demonstrate treatment benefit. In this review, we address the key aspects of HTG pathophysiology and examine the mechanisms and background of current and emerging therapies in the management of HTG.

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  • Current management strategies for hypertriglyceridemia and mixed dyslipidemia provide limited and inconsistent benefits in triglyceride lowering and cardiovascular outcomes.

    “Current management strategies for HTG and mixed dyslipidemia provide limited and inconsistent benefits in TG lowering and cardiovascular outcomes, underscoring the need for more effective and durable approaches targeting TRL and apoB-containing lipoproteins (Filtz et al., 2024; Berglund et al., 2012; Chapman et al., 2011).”

    From Efficacy and safety of small interfering RNA (siRNA) therapies for hypertriglyceridemia and mixed dyslipidemia: an updated systematic review and meta-analysis (2026) · cites this paper as Filtz et al., 2024

    The Fibrates section reports that ACCORD and PROMINENT found no cardiovascular-event benefit despite triglyceride reductions of 16% and 26%, and the Omega-3 Fatty Acids section describes mixed cardiovascular trial results (pages not provided). But the Current Treatments table reports substantial triglyceride reductions across several existing strategies. The source therefore supports inconsistent cardiovascular benefits, not a general claim that triglyceride lowering itself is limited or inconsistent. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • Conventional triglyceride-lowering therapies such as fibrates and omega-3 fatty acids often produce only modest reductions in triglyceride levels and have not been shown to reduce the risk of acute pancreatitis.

    “Conventional TG-lowering therapies, such as fibrates and omega-3 fatty acids, often produce only modest reductions in TG levels and have not been shown to reduce the risk of acute pancreatitis [6].”

    From Efficacy of Olezarsen in Severe Hypertriglyceridemia and Acute Pancreatitis Risk: A Systematic Review and Meta-Analysis of Randomized Controlled Trials (2026) · cites this paper as [6]

    The Fibrates section (page unavailable) reports triglyceride reductions of 16%, 26%, and 31% in cited trials, and the Omega-3 Fatty Acids section identifies triglyceride reduction as an effect. But the Acute Pancreatitis section discusses risk from elevated triglycerides, not whether fibrates or omega-3 fatty acids have been shown to prevent pancreatitis; the paper therefore does not support that part of the claim. (LLM, conf=0.82)

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References 158 · Cited by 26

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Authors
Filtz, A., Parihar, S., Greenberg, G. S., Park, C. M., Scotti, A., Lorenzatti, D., Badimon, J. J., Soffer, D. E., Toth, P. P., Lavie, C. J., Bittner, V., Virani, S. S., & Slipczuk, L.
Affiliations
  • Albert Einstein College of Medicine (US)
  • University of Pennsylvania (US)
  • Johns Hopkins University (US)
  • Ochsner Medical Center (US)
  • University of Alabama at Birmingham (US)
  • Aga Khan University (PK)
Corresponding author
Slipczuk, Leandro
ORCID
Venue
American Journal of Preventive Cardiology
Publisher
Elsevier BV
Published
2024-06
Volume
18
Pages
100648
ISSN
2666-6677 (ISSN-L)
DOI
10.1016/j.ajpc.2024.100648
PMC
PMC10998004
OpenAlex
W4393349088
Cited by
26
References
158
Citations by year
2026: 12 · 2025: 10 · 2024: 4
FWCI
7.82
Type
journal article
Language
en
Open access
Licence
Locations
  • American Journal of Preventive Cardiology (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • Digital Commons-TMC (Texas Medical Center) (submittedVersion)
  • eCommons - AKU (Aga Khan University) (submittedVersion, cc-by-nc-nd)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
  • Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
Keywords
hypertriglyceridemia, triglyceride lowering, atherosclerotic cardiovascular disease, acute pancreatitis, residual cardiovascular risk, statin-treated patients, hypertriglyceridemia treatment, genetic and environmental risk factors, insulin resistance

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