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Lipoprotein(a), PCSK9 Inhibition, and Cardiovascular Risk: Insights From the FOURIER Trial
Open accessAbstract
Background: Lipoprotein(a) [Lp(a)] may play a causal role in atherosclerosis. PCSK9 (proprotein convertase subtilisin/kexin 9) inhibitors have been shown to significantly reduce plasma Lp(a) concentration. However, the relationship between Lp(a) levels, PCSK9 inhibition, and cardiovascular risk reduction remains undefined. Methods: Lp(a) was measured in 25 096 patients in the FOURIER trial (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk), a randomized trial of evolocumab versus placebo in patients with established atherosclerotic cardiovascular disease (median follow-up, 2.2 years). Cox models were used to assess the independent prognostic value of Lp(a) and the efficacy of evolocumab for coronary risk reduction by baseline Lp(a) concentration. Results: The median (interquartile range) baseline Lp(a) concentration was 37 (13–165) nmol/L. In the placebo arm, patients with baseline Lp(a) in the highest quartile had a higher risk of coronary heart disease death, myocardial infarction, or urgent revascularization (adjusted hazard ratio quartile 4: quartile 1, 1.22; 95% CI, 1.01–1.48) independent of low-density lipoprotein cholesterol. At 48 weeks, evolocumab significantly reduced Lp(a) by a median (interquartile range) of 26.9% (6.2%–46.7%). The percent change in Lp(a) and low-density lipoprotein cholesterol at 48 weeks in patients taking evolocumab was moderately positively correlated ( r =0.37; 95% CI, 0.36–0.39; P <0.001). Evolocumab reduced the risk of coronary heart disease death, myocardial infarction, or urgent revascularization by 23% (hazard ratio, 0.77; 95% CI, 0.67–0.88) in patients with a baseline Lp(a) >median, and by 7% (hazard ratio, 0.93; 95% CI, 0.80–1.08; P interaction=0.07) in those ≤median. Coupled with the higher baseline risk, the absolute risk reductions, and number needed to treat over 3 years were 2.49% and 40 versus 0.95% and 105, respectively. Conclusions: Higher levels of Lp(a) are associated with an increased risk of cardiovascular events in patients with established cardiovascular disease irrespective of low-density lipoprotein cholesterol. Evolocumab significantly reduced Lp(a) levels, and patients with higher baseline Lp(a) levels experienced greater absolute reductions in Lp(a) and tended to derive greater coronary benefit from PCSK9 inhibition. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01764633.
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“In the FOURIER trial, greater MACE reductions were seen among patients whose highly elevated Lp(a) levels were reduced by evolocumab [193].”
From Established and Emerging Lipid-Lowering Drugs for Primary and Secondary Cardiovascular Prevention (2023) · cites this paper as [193]
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“This finding has also been supported by randomised control trials which shown that PCSK9 inhibition with evolocumab provides modest (16%) reduction in Lp(a) levels in patients with high Lp(a) levels43.”
From Genetic insights into causal effects of lipids and lipid-modifying targets on calcific aortic valve stenosis: a Mendelian randomized study (2025) · cites this paper as [43]
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“The net effect is a muted class response, with Lp(a) typically lowering around 20 to 30%, well below the reductions seen with LDL C and ApoB [25].”
From Oral PCSK9 inhibitors for elevated LDL-C: A systematic review and meta-analysis of randomized trials (2026) · cites this paper as [25]
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“Although recent studies with PCSK9 inhibitors were not designed to target patients with high Lp(a) concentrations, they nevertheless revealed that patients with higher baseline Lp(a) concentration experienced greater absolute reductions in Lp(a) and tended to derive greater clinical benefit from PCSK9 inhibition [27,28].”
From Quantifying atherogenic lipoproteins for lipid-lowering strategies: Consensus-based recommendations from EAS and EFLM (2020) · cites this paper as [27]
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“evolocumab in the FOURIER trial reduced Lp(a) by a median of 26.9% at 48 weeks[2,25], and alirocumab in ODYSSEY OUTCOMES showed a median relative reduction of −23% by 4 months[3,26].”
From Oral PCSK9 inhibitors for elevated LDL-C: A systematic review and meta-analysis of randomized trials (2026) · cites this paper as [25]
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“In contrast, Mendelian randomization studies have consistently demonstrated that lifelong exposure to higher Lp(a) levels is strongly and causally associated with an increased risk of ASCVD [74,75].”
From 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk (2019) · cites this paper as [75]
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Cites
Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease
Sabatine, M. S., Giugliano, R. P., Keech, A. C., Honarpour, N., Wiviott, S. D., Murphy, S. A., Kuder, J. F., Wang, H., Liu, T., Wasserman, S. M., et al. (2017) · New England Journal of Medicine · doi:10.1056/nejmoa1615664 · Cited by 6,138
Self-citationLipoprotein(a) as a cardiovascular risk factor: current status
Nordestgaard, B. G., Chapman, M. J., Ray, K., Borén, J., Andreotti, F., Watts, G. F., Ginsberg, H., Amarenco, P., Catapano, A., Descamps, O. S., et al. (2010) · European Heart Journal · doi:10.1093/eurheartj/ehq386 · Cited by 1,807
(2009) · JAMA · doi:10.1001/jama.2009.1063 · Cited by 1,753
Genetic Variants Associated with Lp(a) Lipoprotein Level and Coronary Disease
Clarke, R., Peden, J. F., Hopewell, J. C., Kyriakou, T., Goel, A., Heath, S. C., Parish, S., Barlera, S., Franzosi, M. G., Rust, S., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0902604 · Cited by 1,671
Effects of extended-release niacin with laropiprant in high-risk patients
The HPS2-THRIVE Collaborative Group (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1300955 · Cited by 1,668
Genetically Elevated Lipoprotein(a) and Increased Risk of Myocardial Infarction
Kamstrup, P. R. (2009) · JAMA · doi:10.1001/jama.2009.801 · Cited by 1,357
Viney, N. J., van Capelleveen, J. C., Geary, R. S., Xia, S., Tami, J. A., Yu, R. Z., Marcovina, S. M., Hughes, S. G., Graham, M. J., Crooke, R. M., et al. (2016) · The Lancet · doi:10.1016/s0140-6736(16)31009-1 · Cited by 754
Self-citationBurgess, S., Ference, B. A., Staley, J. R., Freitag, D. F., Mason, A. M., Nielsen, S. F., Willeit, P., Young, R., Surendran, P., Karthikeyan, S., et al. (2018) · JAMA Cardiology · doi:10.1001/jamacardio.2018.1470 · Cited by 689
Self-citationTsimikas, S., Viney, N. J., Hughes, S. G., Singleton, W., Graham, M. J., Baker, B. F., Burkey, J. L., Yang, Q., Marcovina, S. M., Geary, R. S., et al. (2015) · The Lancet · doi:10.1016/s0140-6736(15)61252-1 · Cited by 460
Reduction in Lipoprotein(a) With PCSK9 Monoclonal Antibody Evolocumab (AMG 145)
Raal, F. J., Giugliano, R. P., Sabatine, M. S., Koren, M. J., Langslet, G., Bays, H. E., Blom, D. J., Eriksson, M., Dent, R. E., Wasserman, S. M., et al. (2014) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2014.01.006 · Cited by 359
Self-citationLipoprotein (a) measurements for clinical application
Marcovina, S. M., & Albers, J. J. (2016) · Journal of Lipid Research · doi:10.1194/jlr.r061648 · Cited by 338
Marcovina, S. M., Koschinsky, M. L., Albers, J. J., & Skarlatos, S. (2003) · Clinical Chemistry · doi:10.1373/clinchem.2003.023689 · Cited by 288
Inflammatory and Cholesterol Risk in the FOURIER Trial
Bohula, E. A., Giugliano, R. P., Leiter, L. A., Verma, S., Park, J.-G., Sever, P. S., Lira Pineda, A., Honarpour, N., Wang, H., Murphy, S. A., et al. (2018) · Circulation · doi:10.1161/circulationaha.118.034032 · Cited by 280
Self-citationEffects of PCSK9 inhibition with alirocumab on lipoprotein metabolism in healthy humans
Reyes-Soffer, G., Pavlyha, M., Ngai, C., Thomas, T., Holleran, S., Ramakrishnan, R., Karmally, W., Nandakumar, R., Fontanez, N., Obunike, J., et al. (2017) · Circulation · doi:10.1161/circulationaha.116.025253 · Cited by 240
Niacin and fibrates in atherogenic dyslipidemia: pharmacotherapy to reduce cardiovascular risk
Chapman, M. J., Redfern, J. S., McGovern, M. E., & Giral, P. (2010) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2010.01.008 · Cited by 227
Lipoprotein(a) for Risk Assessment in Patients With Established Coronary Artery Disease
O’Donoghue, M. L., Morrow, D. A., Tsimikas, S., Sloan, S., Ren, A. F., Hoffman, E. B., Desai, N. R., Solomon, S. D., DOMANSKI, M. J., Arai, K., et al. (2013) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2013.09.042 · Cited by 223
Self-citationDanik, J. S., Rifai, N., Buring, J. E., & Ridker, P. M. (2006) · JAMA · doi:10.1001/jama.296.11.1363 · Cited by 214
Santos, R. D., Raal, F. J., Catapano, A. L., Witztum, J. L., Steinhagen‐Thiessen, E., & Tsimikas, S. (2015) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.114.304549 · Cited by 197
Gencer, B., Kronenberg, F., Stroes, E. S. G., & Mach, F. (2017) · European Heart Journal · doi:10.1093/eurheartj/ehx033 · Cited by 189
Self-citationSmolders, B., Lemmens, R., & Thijs, V. (2007) · Stroke · doi:10.1161/strokeaha.106.480657 · Cited by 179
Desai, N. R., Kohli, P., Giugliano, R. P., O’Donoghue, M. L., Somaratne, R. M., Zhou, J., Hoffman, E. B., Huang, F., Rogers, W. J., Wasserman, S. M., et al. (2013) · Circulation · doi:10.1161/circulationaha.113.001969 · Cited by 179
Self-citationWatts, G. F., Chan, D. C., Somaratne, R. M., Wasserman, S. M., Scott, R. C., Marcovina, S. M., & Barrett, P. H. R. (2018) · European Heart Journal · doi:10.1093/eurheartj/ehy122 · Cited by 155
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Villard, E. F., Thedrez, A., Blankenstein, J., Croyal, M., Tran, T.-T.-T., Poirier, B., Le Bail, J.-C., Illiano, S., Nobécourt, E., Krempf, M., et al. (2016) · JACC: Basic to Translational Science · doi:10.1016/j.jacbts.2016.06.006 · Cited by 113
Current therapies for lowering lipoprotein (a)
van Capelleveen, J. C., van der Valk, F. M., & Stroes, E. S. G. (2015) · Journal of Lipid Research · doi:10.1194/jlr.r053066 · Cited by 97
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Parish, S., Hopewell, J. C., Hill, M. R., Marcovina, S., Valdes-Marquez, E., Haynes, R., Offer, A., Pedersen, T. R., Baigent, C., Collins, R., et al. (2018) · Circulation: Genomic and Precision Medicine · doi:10.1161/circgen.117.001696 · Cited by 93
Self-citationAfshar, M. S., Pilote, L., Dufresne, L., Engert, J. C., & Thanassoulis, G. (2016) · Journal of the American Heart Association · doi:10.1161/jaha.115.003012 · Cited by 89
Gonbert, S., Malinsky, S., Sposito, A. C., Laouenan, H., Doucet, C., Chapman, M. J., & Thillet, J. (2002) · Atherosclerosis · doi:10.1016/s0021-9150(02)00072-2 · Cited by 70
Edmiston, J. B., Brooks, N. A., Tavori, H., Minnier, J., Duell, B., Purnell, J. Q., Kaufman, T. M., Wójcik, C., Vörös, S., Fazio, S., et al. (2017) · Journal of clinical lipidology · doi:10.1016/j.jacl.2017.03.001 · Cited by 43
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Elliott, P. (2009) · JAMA · doi:10.1001/jama.2009.954 · Cited by 35
Lipoprotein(a): the perpetual supporting actor
Gencer, B., & Mach, F. (2018) · European Heart Journal · doi:10.1093/eurheartj/ehy385 · Cited by 14
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Metadata
- Authors
- O’Donoghue, M. L., Fazio, S., Giugliano, R. P., Stroes, E. S. G., Kanevsky, E., Gouni-Berthold, I., Im, K., Lira Pineda, A., Wasserman, S. M., Češka, R., Ezhov, M. V., Jukema, J. W., Jensen, H. K., Tokgözoğlu, S. L., Mach, F., Huber, K., Sever, P. S., Keech, A. C., Pedersen, T. R., & Sabatine, M. S.
- Affiliations
- Brigham and Women's Hospital (US)
- Oregon Health & Science University (US)
- Amsterdam UMC Location University of Amsterdam (NL)
- Polyclinic for Endocrinology, Diabetes and Preventive Medicine, University of Cologne, Germany (I.G.-B.).
- Amgen, Thousand Oaks, CA (A.L.P., S.M.W.).
- Amgen (United States) (US)
- Charles University (CZ)
- National Cardiology Research Center, Moscow, Russia (M.V.E.).
- Leiden University Medical Center (NL)
- Aarhus University (DK)
- Cardiovascular Division, Hacettepe University, Ankara, Turkey (S.L.T.).
- University of Geneva (CH)
- Sigmund Freud Privatuniversität Wien (AT)
- Imperial College London (GB)
- The University of Sydney (AU)
- Oslo University Hospital (NO)
- ORCID
- Venue
- Circulation
- Published
- 2019-03-19
- Volume
- 139
- Issue
- 12
- Pages
- 1483-1492
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2940327706
- Cited by
- 984
- References
- 33
- Citations by year
- 2026: 133 · 2025: 153 · 2024: 157 · 2023: 134 · 2022: 120 · 2021: 100 · 2020: 122 · 2019: 64
- FWCI
- 97.10
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion, cc-by)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Leiden Repository (Leiden University) (submittedVersion)
- Spiral (Imperial College London) (submittedVersion)
- Funders
- Abbott Laboratories
- Amgen
- Bristol-Myers Squibb
- Eli Lilly and Company
- Pfizer
- AstraZeneca
- GlaxoSmithKline
- Sanofi
- Brigham and Women's Hospital
- Gilead Sciences
- Alnylam Pharmaceuticals
- Univerzita Karlova v Praze
- Aarhus Universitet
- Aarhus Universitetshospital
- Regeneron Pharmaceuticals
- Intarcia Therapeutics
- Amarin Corporation
- Medicines Company
- Mylan
- MyoKardia
- Imperial College London
- Universiteit Leiden
- Daiichi-Sankyo
- Eisai
- Novo Nordisk
- Leids Universitair Medisch Centrum
- Universitetet i Oslo
- Hacettepe Üniversitesi
- Université de Genève
- Universität zu Köln
- Novo Nordisk Fonden (NNF18OC0031258)
- Servier
- Esperion Therapeutics
- Medical Research Council
- National Health and Medical Research Council
- Sydney Medical School
- Janssen Research and Development
- Daiichi Sankyo Europe
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Keywords
- lipoprotein(a), PCSK9 inhibitors, evolocumab, cardiovascular risk, atherosclerotic cardiovascular disease, coronary artery disease, myocardial infarction, urgent revascularization, LDL cholesterol, prognostic factors, FOURIER trial, LDL cholesterol lowering
- MeSH terms
- Proprotein Convertase 9, Adult, Aged, Aged, 80 and over, Anticholesteremic Agents, Double-Blind Method, Female, Humans, Cholesterol, LDL, Male, Middle Aged, Risk Factors, Placebo Effect, Proportional Hazards Models, Treatment Outcome, Lipoprotein(a), Atherosclerosis, Antibodies, Monoclonal, Humanized
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