Cited by 145Atherosclerosis and Cardiovascular DiseasesLipoproteins and Cardiovascular HealthInflammasome and immune disorders

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Novel Antiatherosclerotic Therapies

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Libby, Peter, Everett, Brendan M.·2019·Arteriosclerosis, Thrombosis, and Vascular Biology

DOI 10.1161/atvbaha.118.310958PMC PMC6436984

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Abstract

Many measures can control lipid risk factors for atherosclerosis. Yet, even with excellent control of dyslipidemia, other sources of risk remain. Hence, we must look beyond lipids to address residual risk. Lifestyle measures should form the foundation of cardiovascular risk control. Many pharmacological interventions targeting oxidation have proven disappointing. A large program tested inhibition of a LpPLA 2 (lipoprotein-associated phospholipase A 2 ), culminating in 2 large-scale clinical trials that did not meet their primary end points. A variety of antioxidants have not shown benefit in clinical trials. Numerous laboratory and clinical studies have inculpated inflammatory pathways in the pathogenesis of atherosclerotic events. The p38 MAPK (mitogen-activated protein kinase) inhibitor losmapimod and an inhibitor of a leukocyte adhesion molecule, P-selectin, did not alter adverse events in trials. Low-dose methotrexate, despite the promising observational studies, did not lower biomarkers of inflammation or alter cardiovascular outcomes in the CIRT (cardiovascular inflammation reduction trial). Four large-scale investigations underway will determine colchicine’s ability to reduce recurrent events in secondary prevention. The CANTOS (Canakinumab Anti-inflammatory Thrombosis Outcomes Study) showed that an antibody that neutralizes IL (interleukin)-1β can reduce recurrent cardiovascular events in secondary prevention. The success of CANTOS points to the pathway that leads from the NLRP3 (NOD-like receptor family, pyrin domain-containing protein 3) inflammasome through IL-1β to IL-6 as an attractive target for further study and clinical development beyond lipid therapies to address the unacceptable burden of risk that remains despite our best current care in secondary prevention.

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Authors: Libby, P., & Everett, B. M.
Affiliations: Brigham and Women's Hospital (US)
Corresponding author: Libby, Peter
ORCID: Libby, Peter
Everett, Brendan M.
Venue: Arteriosclerosis, Thrombosis, and Vascular Biology
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2019-04
Volume: 39
Issue: 4
Pages: 538-545
ISSN: 1079-5642 (ISSN-L)
1524-4636
DOI: 10.1161/atvbaha.118.310958
PMC: PMC6436984
OpenAlex: W2917926925
Cited by: 145
References: 83
Citations by year: 2026: 11 · 2025: 18 · 2024: 11 · 2023: 18 · 2022: 27 · 2021: 29 · 2020: 20 · 2019: 11
FWCI: 1.88
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Arteriosclerosis Thrombosis and Vascular Biology (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: American Heart Association (18CSA34080399)
National Heart, Lung, and Blood Institute (R01HL080472)
Topics: Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
Keywords: atherosclerosis, antiatherosclerotic therapy, residual cardiovascular risk, dyslipidemia, antioxidants, inflammation, p38 MAPK inhibition, P-selectin, methotrexate, colchicine, IL-1β, NLRP3 inflammasome, interleukin-6, secondary prevention, CANTOS trial
MeSH terms: Anti-Inflammatory Agents, Antioxidants, Clinical Trials as Topic, Clone Cells, Hematopoiesis, Humans, Inflammation, Life Style, Risk Factors, Vaccination, Therapies, Investigational, Atherosclerosis, Molecular Targeted Therapy, Antibodies, Monoclonal, Humanized

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