The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.
PCSK9 (Proprotein convertase subtilisin/kexin type 9) inhibitors: past, present, and the future
Abstract
Reduction in low-density lipoprotein cholesterol (LDL-C), mainly with statins, has decreased the risk of cardiovascular events over the last few decades. However, there are several patient populations that warrant further decrease in LDL-C by additional cholesterol-lowering therapy other than statins. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are a new class of drugs that have been shown to further decrease LDL-C by 50-70% when administered as a monotherapy or on a background therapy with statins. Proprotein convertase subtilisin/kexin type 9 inhibitors are also an excellent example of drug development in which discovery of gene mutations and its clinical effects have rapidly progressed into successful preclinical and clinical studies with multiple Phases 1-3 clinical trials completed or ongoing to date. This review summarizes the rapid evolution of the drug from genetic discovery to identification of targets for the drugs, to animal and human testing, and to large clinical outcomes trials, followed by discussion on foreseeable challenges of PCSK9 inhibitors.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Repatha, a marketed PCSK9 monoclonal antibody, has demonstrated the ability to rapidly decrease LDL-C levels by 50–70% and lower the risk of myocardial infarction or stroke in multiple completed and ongoing clinical trials11,12.”
From ABCC4 impairs the clearance of plasma LDL cholesterol through suppressing LDLR expression in the liver (2025) · cites this paper as [11]
Citations
Cites
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
Cohen, J., Pertsemlidis, A., Kotowski, I. K., Graham, R., Garcia, C. K., & Hobbs, H. H. (2005) · Nature Genetics · doi:10.1038/ng1509 · Cited by 1,381
Boekholdt, S. M., Arsenault, B. J., Mora, S., Pedersen, T. R., LaRosa, J. C., Nestel, P. J., Simes, R. J., Durrington, P., Hitman, G. A., Welch, K. M. A., et al. (2012) · JAMA · doi:10.1001/jama.2012.366 · Cited by 795
A 52-Week Placebo-Controlled Trial of Evolocumab in Hyperlipidemia
Blom, D. J., Hala, T., Bolognese, M., Lillestol, M. J., Toth, P. D., Burgess, L., Ceska, R., Roth, E., Koren, M. J., Ballantyne, C. M., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1316222 · Cited by 720
Effect of a Monoclonal Antibody to PCSK9 on LDL Cholesterol
Stein, E. A., Mellis, S., Yancopoulos, G. D., Stahl, N., Logan, D., Smith, W. B., Lisbon, E., Gutierrez, M., Webb, C., Wu, R., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1105803 · Cited by 664
Poirier, S., Mayer, G., Benjannet, S., Bergeron, E., Marcinkiewicz, J., Nassoury, N., Mayer, H., Nimpf, J., Prat, A., & Seidah, N. G. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m708098200 · Cited by 477
Research works printed but not linked: 65
- 10.1373/clinchem.2010.159350 · DOI
- 10.1161/CIRCOUTCOMES.110.959247 · DOI · Paper page
- 10.1016/S0140-6736(05)67394-1 · DOI · Paper page
- 10.1007/s00392-006-0403-x · DOI · Paper page
- 10.1016/j.jacc.2009.10.042 · DOI
- 10.1042/bse0380079 · DOI
- 10.1073/pnas.0335507100 · DOI · Paper page
- 10.1016/j.abb.2003.09.011 · DOI
- 10.1074/jbc.M409699200 · DOI · Paper page
- 10.1038/nsmb1235 · DOI · Paper page
- 10.1038/ng1161 · DOI · Paper page
- 10.1002/humu.9383 · DOI
- 10.1007/s00109-005-0019-z · DOI
- 10.1097/01.mol.0000162321.31925.a3 · DOI · Paper page
- 10.1136/jmg.2006.038356 · DOI · Paper page
- 10.1016/j.jacc.2010.02.044 · DOI
- 10.1016/j.atherosclerosis.2006.08.039 · DOI
- 10.1161/CIRCGENETICS.108.828467 · DOI
- 10.1016/j.atherosclerosis.2008.03.009 · DOI
- 10.1161/ATVBAHA.109.194191 · DOI
- 10.1086/507488 · DOI
- 10.1073/pnas.0903849106 · DOI · Paper page
- 10.7150/ijbs.3524 · DOI
- 10.1194/jlr.M011445 · DOI
- 10.1073/pnas.0805434105 · DOI
- 10.1016/S0140-6736(13)61914-5 · DOI
- 10.1371/journal.pone.0010682 · DOI · Paper page
- 10.1194/jlr.C600025-JLR200 · DOI
- 10.1038/mt.2011.260 · DOI
- 10.1007/s11886-013-0391-1 · DOI
- 10.1074/jbc.M702027200 · DOI · Paper page
- 10.1172/JCI29383 · DOI · Paper page
- 10.1016/j.bbrc.2008.04.004 · DOI
- 10.1073/pnas.0409736102 · DOI · Paper page
- 10.1073/pnas.0501652102 · DOI · Paper page
- 10.1373/clinchem.2007.091280 · DOI
- Tavori, 2014, On the function and homeostasis of PCSK9: Reciprocal interaction with LDLR and additional lipid effects, Atherosclerosis, 238, 264, 10.1016/j.atherosclerosis.2014.12.017 · DOI · Paper page
- 10.1016/j.jacc.2012.03.007 · DOI
- 10.1016/S0140-6736(12)61770-X · DOI
- 10.1016/j.jacc.2012.08.986 · DOI
- 10.1056/NEJMoa1201832 · DOI
- 10.1001/jama.2014.4030 · DOI · Paper page
- 10.1016/j.ijcard.2014.06.049 · DOI
- 10.1161/CIRCULATIONAHA.113.007012 · DOI
- Cannon, 2015, Efficacy and safety of alirocumab in high cardiovascular risk patients with inadequately controlled hypercholesterolaemia on maximally tolerated doses of statins: the ODYSSEY COMBO II randomized controlled trial, Eur Heart J, 10.1093/eurheartj/ehv028 · DOI
- 10.1093/eurheartj/eht273 · DOI · Paper page
- 10.1016/j.atherosclerosis.2007.12.024 · DOI
- 10.1111/j.1365-2796.2004.01405.x · DOI
- 10.1016/j.amjcard.2008.07.035 · DOI
- 10.1016/j.atherosclerosis.2009.09.014 · DOI · Paper page
- Robinson, 2013, Management of familial hypercholesterolemia: a review of the recommendations from the National Lipid Association Expert Panel on Familial Hypercholesterolemia, J Manag Care Pharm, 19, 139, 10.18553/jmcp.2013.19.2.139 · DOI
- 10.1016/j.jacc.2004.03.046 · DOI
- 10.1161/01.cir.0000457464.79076.2c · DOI
- 10.1586/14779072.6.7.955 · DOI · Paper page
- Bays, 2014, Efficacy and safety of combining alirocumab with atorvastatin or rosuvastatin versus statin intensification or adding ezetimibe in high cardiovascular risk patients: ODYSSEY OPTIONS I and II, Circulation, 130, 2118
- Efficacy and safety of alirocumab in patients with heterozygous familial hypercholesterolaemia not adequately controlled with current lipid-lowering therapy: results of ODYSSEY FH I and FH II studies. http://www.escardio.org/congresses/esc-2014/congress-reports/Pages/707-3-Hotline3-ODYSSEY-COMBO-FH.aspx#presenter2 (28 April 2015). · DOI
- Etemad, 2005, Total first-year costs of acute coronary syndrome in a managed care setting, J Manag Care Pharm, 11, 300, 10.18553/jmcp.2005.11.4.300 · DOI
- 10.1503/cmaj.101281 · DOI
- 10.1007/s11936-006-0049-z · DOI
- 10.1185/03007990903494934 · DOI
- 10.1056/NEJMoa1501031 · DOI · Paper page
- 10.1016/j.jacc.2013.07.056 · DOI
- 10.1038/nrcardio.2014.84 · DOI
- Koren, 2015, Safety and efficacy of alirocumab 150 mg every 2 weeks, a fully human proprotein convertase subtilisin/kexin type 9 monoclonal antibody: A Phase II pooled analysis, Postgrad Med, 127, 125, 10.1080/00325481.2015.998987 · DOI
- 10.3390/nu6125517 · DOI
Cited by
Sorted by citations
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
Wintjens, R., Bozon, D., Belabbas, K., MBou, F., Girardet, J.-P., Tounian, P., Jolly, M., Boccara, F., Cohen, A., Karsenty, A., et al. (2016) · Journal of Lipid Research · doi:10.1194/jlr.p055699 · Cited by 47
Durairaj, A., Sabates, A., Nieves, J., Moraes, B., & Baum, S. (2017) · Current Treatment Options in Cardiovascular Medicine · doi:10.1007/s11936-017-0556-0 · Cited by 27
Francis, G. S. (2017) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2017.08.068 · Cited by 8
Chen, J., Huang, H., Chen, C., Xia, G., Huang, H., Xiong, Y., Luo, P., Chen, Y., Li, J., Wen, L., et al. (2025) · Communications Biology · doi:10.1038/s42003-025-08818-x · Cited by 1
Metadata
- Authors
- Shimada, Y. J., & Cannon, C. P.
- Venue
- European Heart Journal
- Publisher
- Oxford University Press (OUP)
- Published
- 2015-05-12
- Volume
- 36
- Issue
- 36
- Pages
- 2415-2424
- ISSN
- 0195-668X
- 1522-9645
- Cited by
- 98
- References
- 6
- Language
- en
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review