The DOI matches its Crossref record; 126 of the 129 references it cites were found in a registry or an index.
The Evolving Future of PCSK9 Inhibitors
Open accessAbstract
Variants in proprotein convertase subtilisin/kexin type 9 (PCSK9) provide insights into mechanisms regulating low-density lipoprotein (LDL) levels. Human monoclonal antibodies that target PCSK9 lower LDL cholesterol (LDL-C) levels by 55% to 72% in different high-risk patient groups. Clinical trials with PCSK9 inhibitors have demonstrated reductions in atherosclerotic cardiovascular disease events, particularly in patients with recent acute coronary syndrome, multivessel coronary artery disease, or peripheral arterial disease. Commonly observed profound reductions in LDL-C to levels <25 mg/dl have been accompanied by even lower rates of atherosclerotic cardiovascular disease events, thus supporting the concept that there may be no lower limit for LDL-C. Aggressive LDL-C lowering with fully human PCSK9 monoclonal antibodies has been accompanied by a safety profile that has been very favorable. On the basis of clinical trial evidence, LDL lowering with PCSK9 inhibitors is recommended for high-risk patients with LDL-C levels ≥70 mg/dl on maximally tolerated oral therapies including statins and/or ezetimibe.
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“Patients with receptor-negative HoFH derive minimal benefit from PCSK9-targeted therapy, whereas receptor-defective HoFH and heterozygous FH (HeFH) patients exhibit clinically meaningful LDL-C reductions [84].”
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“This concept is likely to be relevant to humans because dramatic reductions in plasma LDL-cholesterol levels lead to the regression of even advanced atherosclerotic lesions, and plaque regression is accompanied by lower rates of atherosclerotic cardiovascular disease events210,211.”
From Inflammation and its resolution in atherosclerosis: mediators and therapeutic opportunities (2019) · cites this paper as [211]
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Stone, N. J., Robinson, J. G., Lichtenstein, A. H., Bairey Merz, C. N., Blum, C. B., Eckel, R. H., Goldberg, A. C., Gordon, D., Levy, D., Lloyd-Jones, D. M., et al. (2014) · Circulation · doi:10.1161/01.cir.0000437738.63853.7a · Cited by 7,081
Grundy, S. M., Cleeman, J. I., Merz, C. N. B., Brewer, H. B., Clark, L. T., Hunninghake, D. B., Pasternak, R. C., Smith, S. C., & Stone, N. J. (2004) · Circulation · doi:10.1161/01.cir.0000133317.49796.0e · Cited by 6,902
Cholesterol Treatment Trialists' (CTT) Collaboration (2010) · The Lancet · doi:10.1016/s0140-6736(10)61350-5 · Cited by 6,550
Intensive versus Moderate Lipid Lowering with Statins after Acute Coronary Syndromes
Cannon, C. P., Braunwald, E., McCabe, C. H., Rader, D. J., Rouleau, J. L., Belder, R., Joyal, S. V., Hill, K. A., Pfeffer, M. A., & Skene, A. M. (2004) · New England Journal of Medicine · doi:10.1056/nejmoa040583 · Cited by 4,938
Self-citationEzetimibe Added to Statin Therapy after Acute Coronary Syndromes
Cannon, C. P., Blazing, M. A., Giugliano, R. P., McCagg, A., White, J. A., Theroux, P., Darius, H., Lewis, B. S., Ophuis, T. O., Jukema, J. W., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1410489 · Cited by 4,487
Self-citationFerence, B. A., Ginsberg, H. N., Graham, I., Ray, K. K., Packard, C. J., Bruckert, E., Hegele, R. A., Krauss, R. M., Raal, F. J., Schunkert, H., et al. (2017) · European Heart Journal · doi:10.1093/eurheartj/ehx144 · Cited by 3,962
Self-citationStone, N. J., Robinson, J. G., Lichtenstein, A. H., Bairey Merz, C. N., Blum, C. B., Eckel, R. H., Goldberg, A. C., Gordon, D., Levy, D., Lloyd-Jones, D. M., et al. (2014) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2013.11.002 · Cited by 3,845
Intensive Lipid Lowering with Atorvastatin in Patients with Stable Coronary Disease
LaRosa, J. C., Grundy, S. M., Waters, D. D., Shear, C., Barter, P., Fruchart, J.-C., Gotto, A. M., Greten, H., Kastelein, J. J. P., Shepherd, J., et al. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa050461 · Cited by 3,489
Sequence Variations in PCSK9, Low LDL, and Protection against Coronary Heart Disease
Cohen, J. C., Boerwinkle, E., Mosley, T. H., & Hobbs, H. H. (2006) · New England Journal of Medicine · doi:10.1056/nejmoa054013 · Cited by 3,181
Research works printed but not linked: 4
- Kastelein, 2015, ODYSSEY FH I and FH II: 78 week results with alirocumab treatment in 735 patients with heterozygous familial hypercholesterolaemia, Eur Heart J, 36, 2996
- Hopkins, 2015, Characterization of autosomal dominant hypercholesterolemia caused by PCSK9 gain of function mutations and its specific treatment with alirocumab, a PCSK9 monoclonal antibody, Circ Cardiovasc Genet, 8, 823, 10.1161/CIRCGENETICS.115.001129 · DOI
- Institute for Clinical and Economic Review posts updated economic analyses for PCSK9 inhibitor evolocumab, finds less favorable cost-effectiveness [press release]. Boston, MA: ICER; September 11, 2017. Available at: https://icer-review.org/announcements/pcsk9-neu/. Accessed April 4, 2018.
- Institute for Clinical and Economic Review updates value-based price benchmark for alirocumab, a PCSK9 inhibitor for treatment of high cholesterol [press release]. Boston, MA: ICER; March 10, 2018. Available at: https://icer-review.org/announcements/alirocumab-prelim-evidence-update/. Accessed April 4, 2018.
Cited by
Sorted by citations
Inflammation and its resolution in atherosclerosis: mediators and therapeutic opportunities
Bäck, M., Yurdagul, A., Tabas, I., Öörni, K., & Kovanen, P. T. (2019) · Nature Reviews Cardiology · doi:10.1038/s41569-019-0169-2 · Cited by 1,341
Guedeney, P., Giustino, G., Sorrentino, S., Claessen, B. E., Camaj, A., Kalkman, D. N., Vogel, B., Sartori, S., De Rosa, S., Baber, U., et al. (2022) · European Heart Journal · doi:10.1093/eurheartj/ehz430 · Cited by 208
Self-citationCoronary Atherosclerotic Plaque Regression
Dawson, L. P., Lum, M., Nerlekar, N., Nicholls, S. J., & Layland, J. J. (2022) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2021.10.035 · Cited by 209
Lipid-Lowering Agents: Targets Beyond PCSK9
Hegele, R. A., & Tsimikas, S. (2019) · Circulation Research · doi:10.1161/circresaha.118.313171 · Cited by 171
Self-citationFamilial Hypercholesterolemia: The Most Frequent Cholesterol Metabolism Disorder Caused Disease
Benito‐Vicente, A., Uribe, K. B., Jebari‐Benslaiman, S., Galicia-García, U., Ostolaza, H., & Martín, C. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19113426 · Cited by 151
Metadata
- Authors
- Rosenson, R. S., Hegele, R. A., Fazio, S., & Cannon, C. P.
- Affiliations
- Mount Sinai Hospital (US)
- Western University (CA)
- Oregon Health & Science University (US)
- Brigham and Women's Hospital (US)
- Corresponding author
- Rosenson, Robert S.
- Venue
- Journal of the American College of Cardiology
- Publisher
- Elsevier BV
- Published
- 2018-07
- Volume
- 72
- Issue
- 3
- Pages
- 314-329
- ISSN
- 0735-1097 (ISSN-L)
- OpenAlex
- W2848978533
- Cited by
- 264
- References
- 129
- Citations by year
- 2026: 18 · 2025: 39 · 2024: 34 · 2023: 47 · 2022: 31 · 2021: 35 · 2020: 27 · 2019: 26 · 2018: 7
- FWCI
- 5.28
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of the American College of Cardiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Amgen
- Pfizer
- AstraZeneca
- Sanofi
- American College of Cardiology Foundation
- Regeneron Pharmaceuticals
- Kowa Company
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Keywords
- PCSK9 inhibitors, PCSK9, LDL cholesterol lowering, monoclonal antibodies, atherosclerotic cardiovascular disease, acute coronary syndrome, multivessel coronary artery disease, peripheral arterial disease, hypercholesterolemia
- MeSH terms
- Proprotein Convertase 9, PCSK9 Inhibitors, Antibodies, Monoclonal, Anticholesteremic Agents, Cardiovascular Diseases, Clinical Trials as Topic, Humans, Hypercholesterolemia, Cholesterol, LDL, Treatment Outcome, Antibodies, Monoclonal, Humanized
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