The DOI matches its Crossref record; 83 of the 83 references it cites were found in a registry or an index.
Novel Antiatherosclerotic Therapies
Open accessAbstract
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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“These trials highlighted the potential, but also the limitations of current anti-inflammatory approaches, including immune suppression and the associated risk of sepsis.4”
From Senescence-induced inflammation: an important player and key therapeutic target in atherosclerosis (2020) · cites this paper as [4]
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Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease
Ridker, P. M., Everett, B. M., Thuren, T., MacFadyen, J. G., Chang, W. H., Ballantyne, C., Fonseca, F., Nicolau, J., Koenig, W., Anker, S. D., et al. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1707914 · Cited by 9,482
Self-citationAge-related clonal hematopoiesis associated with adverse outcomes
Jaiswal, S., Fontanillas, P., Flannick, J., Manning, A., Grauman, P. V., Mar, B. G., Lindsley, R. C., Mermel, C. H., Burtt, N., Chavez, A., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1408617 · Cited by 4,841
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Inflammation in Atherosclerosis
Libby, P. (2012) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.108.179705 · Cited by 3,796
Self-citationCardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia
Bhatt, D. L., Steg, P. G., Miller, M., Brinton, E. A., Jacobson, T. A., Ketchum, S. B., Doyle, R. T., Juliano, R. A., Jiao, L., Granowitz, C., et al. (2019) · New England Journal of Medicine · doi:10.1056/nejmoa1812792 · Cited by 3,317
Activation and regulation of the inflammasomes
Latz, E., Xiao, T. S., & Stutz, A. (2013) · Nature Reviews Immunology · doi:10.1038/nri3452 · Cited by 2,884
A small-molecule inhibitor of the NLRP3 inflammasome for the treatment of inflammatory diseases
Coll, R. C., Robertson, A. A. B., Chae, J. J., Higgins, S. C., Muñoz-Planillo, R., Inserra, M. C., Vetter, I., Dungan, L. S., Monks, B. G., Stutz, A., et al. (2015) · Nature Medicine · doi:10.1038/nm.3806 · Cited by 2,849
Clonal hematopoiesis and risk of atherosclerotic cardiovascular disease
Jaiswal, S., Natarajan, P., Silver, A. J., Gibson, C. J., Bick, A. G., Shvartz, E., McConkey, M., Gupta, N., Gabriel, S., Ardissino, D., et al. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1701719 · Cited by 2,683
Self-citationA novel heterodimeric cysteine protease is required for interleukin-1βprocessing in monocytes
Thornberry, N. A., Bull, H. G., Calaycay, J. R., Chapman, K. T., Howard, A. D., Kostura, M. J., Miller, D. K., Molineaux, S. M., Weidner, J. R., Aunins, J. G., et al. (1992) · Nature · doi:10.1038/356768a0 · Cited by 2,613
Inflammation in Atherosclerosis
Libby, P., Ridker, P. M., & Hansson, G. K. (2009) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2009.09.009 · Cited by 2,228
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Research works printed but not linked: 1
- Pascal, B. Pascal’s Pensées. New York, NY: E.P. Dutton; 1958; section 233.
Cited by
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The changing landscape of atherosclerosis
Libby, P. (2021) · Nature · doi:10.1038/s41586-021-03392-8 · Cited by 2,873
Self-citationNAFLD and cardiovascular diseases: a clinical review
Kasper, P., Martin, A., Lang, S., Kütting, F., Goeser, T., Demir, M., & Steffen, H. (2020) · Clinical Research in Cardiology · doi:10.1007/s00392-020-01709-7 · Cited by 691
Targeting cardiovascular inflammation: next steps in clinical translation
Lawler, P. R., Bhatt, D. L., Godoy, L. C., Lüscher, T. F., Bonow, R. O., Verma, S., & Ridker, P. M. (2020) · European Heart Journal · doi:10.1093/eurheartj/ehaa099 · Cited by 463
Immune Pathways in Etiology, Acute Phase, and Chronic Sequelae of Ischemic Stroke
Endres, M., Moro, M. Á., Nolte, C. H., Dames, C., Buckwalter, M. S., & Meisel, A. (2022) · Circulation Research · doi:10.1161/circresaha.121.319994 · Cited by 359
Inflammation in Atherosclerosis—No Longer a Theory
Libby, P. (2020) · Clinical Chemistry · doi:10.1093/clinchem/hvaa275 · Cited by 333
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Metadata
- Authors
- Libby, P., & Everett, B. M.
- Affiliations
- Brigham and Women's Hospital (US)
- Corresponding author
- Libby, Peter
- Venue
- Arteriosclerosis, Thrombosis, and Vascular Biology
- Published
- 2019-04
- Volume
- 39
- Issue
- 4
- Pages
- 538-545
- ISSN
- 1079-5642 (ISSN-L)
- 1524-4636
- 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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