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An Exploratory Analysis of Proprotein Convertase Subtilisin/Kexin Type 9 Inhibition and Aortic Stenosis in the FOURIER Trial
Open accessAbstract
Importance: Despite recent advances in treatment of severe aortic valve stenosis (AS), AS remains a life-threatening condition with no proven disease-modifying therapy. Low-density lipoprotein cholesterol (LDL-C) and lipoprotein(a) (Lp[a]) have been implicated in the pathobiology of AS. The proprotein convertase subtilisin/kexin type 9 inhibitor evolocumab reduces circulating LDL-C concentrations by 50% to 60% and Lp(a) by 20% to 30%. Objective: To determine whether evolocumab reduces the risk of AS events in patients with atherosclerotic cardiovascular disease. Interventions: Patients were randomized 1:1 to evolocumab or placebo. Design, Setting, and Participants: Exploratory analysis of the FOURIER trial, which enrolled 27 564 patients with stable atherosclerotic cardiovascular disease who were taking statin therapy at 1242 sites in 49 countries from February 2013 to November 2016. Patients were randomized to evolocumab or placebo and followed up for a median (interquartile range) of 2.2 (1.8-2.5) years. This post hoc analysis was performed from September 2019 to February 2020. Main Outcomes and Measures: Site-reported adverse events of new or worsening AS or aortic valve replacement (termed AS events). The adjusted risk of AS events was calculated with a multivariable model including concentrations of Lp(a) and LDL-C corrected for Lp(a) content, plus age, sex, diabetes, hypertension, current smoking, and estimated glomerular filtration rate. Evolocumab efficacy was tested using a Cox proportional hazards model. Results: Aortic stenosis events occurred in 63 patients (48 men [76%]; mean [SD] age, 69 [9] years) over a median of 2.2 years. Elevated Lp(a) concentration was associated with higher rates of AS events (adjusted hazard ratio [aHR], 1.55 [95% CI, 1.17-2.05] per SD; P = .002), including aortic valve replacement (aHR, 2.22 [95% CI, 1.38-3.58] per SD; P = .001), after multivariable adjustment. The corrected LDL-C concentration was not significantly associated with AS events (aHR, 1.23 [95% CI, 0.93-1.61] per SD; P = .14). The overall HR for AS events with evolocumab was 0.66 (95% CI, 0.40-1.09), with no apparent association in the first year (HR, 1.09 [95% CI, 0.48-2.47]) but an HR of 0.48 (95% CI, 0.25-0.93) after the first year of treatment. Conclusions and Relevance: In this exploratory analysis of the FOURIER trial, higher Lp(a) levels, but not Lp(a)-corrected LDL-C levels, were associated with a higher risk of subsequent AS events, including aortic valve replacement. Long-term therapy with evolocumab may reduce AS events, and this raises the possibility that specific pharmacologic lipid-lowering therapy could offer a means to prevent or slow the progression of AS. These exploratory findings merit further investigation with a dedicated randomized clinical trial. Trial Registration: ClinicalTrials.gov Identifier: NCT01764633.
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“Exploratory analyses suggest that long-term treatment with evolocumab may reduce the risk of aortic valve stenosis events [53].”
From Identifying novel drug targets for calcific aortic valve disease through Mendelian randomization (2025) · cites this paper as [53]
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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-citationClinical Factors Associated With Calcific Aortic Valve Disease
Stewart, B. F., Siscovick, D., Lind, B. K., Gardin, J. M., Gottdiener, J. S., Smith, V. E., Kitzman, D. W., & Otto, C. M. (1997) · Journal of the American College of Cardiology · doi:10.1016/s0735-1097(96)00563-3 · Cited by 2,029
Intensive Lipid Lowering with Simvastatin and Ezetimibe in Aortic Stenosis
Rossebø, A. B., Pedersen, T. R., Boman, K., Brudi, P., Chambers, J. B., Egstrup, K., Gerdts, E., Gohlke-Bärwolf, C., Holme, I., Kesäniemi, Y. A., et al. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa0804602 · Cited by 1,644
Self-citationA Randomized Trial of Intensive Lipid-Lowering Therapy in Calcific Aortic Stenosis
Cowell, S. J., Newby, D. E., Prescott, R. J., Bloomfield, P., Reid, J., Northridge, D. B., & Boon, N. A. (2005) · New England Journal of Medicine · doi:10.1056/nejmoa043876 · Cited by 1,146
Genetic Associations with Valvular Calcification and Aortic Stenosis
Thanassoulis, G., Campbell, C. Y., Owens, D. S., Smith, J. G., Smith, A. V., Peloso, G. M., Kerr, K. F., Pechlivanis, S., Budoff, M. J., Harris, T. B., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1109034 · Cited by 1,008
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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., et al. (2019) · Circulation · doi:10.1161/circulationaha.118.037184 · Cited by 984
Self-citationChan, K. L., Teo, K., Dumesnil, J. G., Ni, A., & Tam, J. (2010) · Circulation · doi:10.1161/circulationaha.109.900027 · Cited by 815
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Bittner, V. A., Szarek, M., Aylward, P. E., Bhatt, D. L., Diaz, R., Edelberg, J. M., Fras, Z., Goodman, S. G., Halvorsen, S., Hanotin, C., et al. (2020) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2019.10.057 · Cited by 572
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Capoulade, R., Chan, K. L., Yeang, C., Mathieu, P., Bossé, Y., Dumesnil, J. G., Tam, J. W., Teo, K. K., Mahmut, A., Yang, X., et al. (2015) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2015.07.020 · Cited by 417
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Ferreira, S. M., Üstünkaya, T., Siddiqui, M., Kukendrarajah, K., Schmidt, F., Ahmed, R., Khanji, M. Y., Chahal, A., Verwerft, J., & Providencia, R. A. (2026) · EBioMedicine · doi:10.1016/j.ebiom.2026.106499 · Cited by 1
Metadata
- Authors
- Bergmark, B. A., O’Donoghue, M. L., Murphy, S. A., Kuder, J. F., Ezhov, M. V., Ceška, R., Gouni-Berthold, I., Jensen, H. K., Tokgozoglu, S. L., Mach, F., Huber, K., Gaciong, Z., Lewis, B. S., Schiele, F., Jukema, J. W., Pedersen, T. R., Giugliano, R. P., & Sabatine, M. S.
- Affiliations
- Brigham and Women's Hospital (US)
- National Medical Research Center of Cardiology, Moscow, Russia
- Third Internal Medicine Clinic, Center for Preventive Cardiology, University General Hospital, First Medical Faculty, Charles University, Prague, Czech Republic
- Polyclinic for Endocrinology, Diabetes and Preventive Medicine, University of Cologne, Cologne, Germany
- Aarhus University (DK)
- Hacettepe University (TR)
- University Hospital of Geneva (CH)
- Sigmund Freud Privatuniversität Wien (AT)
- Medical University of Warsaw (PL)
- Technion – Israel Institute of Technology (IL)
- University Hospital Center Besançon, Besançon, France
- Leiden University Medical Center (NL)
- Oslo University Hospital (NO)
- Corresponding author
- Bergmark, Brian A.
- ORCID
- Venue
- JAMA Cardiology
- Publisher
- American Medical Association (AMA)
- Published
- 2020-06-01
- Volume
- 5
- Issue
- 6
- Pages
- 709
- ISSN
- 2380-6583 (ISSN-L)
- PMC
- PMC7301224
- OpenAlex
- W3018871408
- Cited by
- 137
- References
- 15
- Citations by year
- 2026: 18 · 2025: 27 · 2024: 29 · 2023: 18 · 2022: 20 · 2021: 12 · 2020: 13
- FWCI
- 14.39
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- JAMA Cardiology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Kölner Universitäts PublikationsServer (Universität zu Köln) (publishedVersion)
- Archive ouverte UNIGE (University of Geneva) (publishedVersion)
- Leiden Repository (Leiden University) (submittedVersion, cc-by-nc-nd)
- Data Archiving and Networked Services (DANS) (submittedVersion, cc-by-nc-nd)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- Funders
- Amgen
- Bristol-Myers Squibb
- Eli Lilly and Company
- Pfizer
- AstraZeneca
- GlaxoSmithKline
- Sanofi
- Brigham and Women's Hospital
- Boston Scientific Corporation
- Regeneron Pharmaceuticals
- Jazz Pharmaceuticals
- Intarcia Therapeutics
- Amarin Corporation
- Medicines Company
- IFM Therapeutics
- Kowa Company
- Mylan
- Bayer HealthCare
- Daiichi-Sankyo
- Eisai
- Novo Nordisk (NNF18OC0031258)
- Novo Nordisk Fonden (NNF18OC0031258)
- Servier
- Esperion Therapeutics
- Netherlands Heart Institute
- Janssen Research and Development
- Daiichi Sankyo Europe
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Valve Diseases and Treatments
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Keywords
- aortic stenosis, evolocumab, PCSK9 inhibition, lipoprotein(a), LDL cholesterol, aortic valve replacement, atherosclerotic cardiovascular disease, FOURIER trial, disease-modifying therapy, statin therapy, cardiovascular risk factors, aortic valve replacement timing, aortic stenosis progression
- MeSH terms
- PCSK9 Inhibitors, Anticholesteremic Agents, Aortic Valve Stenosis, Female, Humans, Cholesterol, LDL, Male, Middle Aged, Risk Factors, Treatment Outcome, Subtilisin, Antibodies, Monoclonal, Humanized
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