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Cited by 150Lipoproteins and Cardiovascular HealthAcute Myocardial Infarction ResearchAntiplatelet Therapy and Cardiovascular Diseases

Lipoprotein(a) and Benefit of PCSK9 Inhibition in Patients With Nominally Controlled LDL Cholesterol

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Schwartz, Gregory G., Szarek, Michael, Bittner, Vera A., Diaz, Rafael, Goodman, Shaun G., Jukema, J. Wouter, Landmesser, Ulf, López-Jaramillo, Patricio +1742 more·2021·Journal of the American College of Cardiology
DOI 10.1016/j.jacc.2021.04.102PMC PMC8822604
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Abstract

BACKGROUND: Guidelines recommend nonstatin lipid-lowering agents in patients at very high risk for major adverse cardiovascular events (MACE) if low-density lipoprotein cholesterol (LDL-C) remains ≥70 mg/dL on maximum tolerated statin treatment. It is uncertain if this approach benefits patients with LDL-C near 70 mg/dL. Lipoprotein(a) levels may influence residual risk. OBJECTIVES: In a post hoc analysis of the ODYSSEY Outcomes (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) trial, the authors evaluated the benefit of adding the proprotein subtilisin/kexin type 9 inhibitor alirocumab to optimized statin treatment in patients with LDL-C levels near 70 mg/dL. Effects were evaluated according to concurrent lipoprotein(a) levels. METHODS: ODYSSEY Outcomes compared alirocumab with placebo in 18,924 patients with recent acute coronary syndromes receiving optimized statin treatment. In 4,351 patients (23.0%), screening or randomization LDL-C was <70 mg/dL (median 69.4 mg/dL; interquartile range: 64.3-74.0 mg/dL); in 14,573 patients (77.0%), both determinations were ≥70 mg/dL (median 94.0 mg/dL; interquartile range: 83.2-111.0 mg/dL). RESULTS: = 0.43. CONCLUSIONS: In patients with recent acute coronary syndromes and LDL-C near 70 mg/dL on optimized statin therapy, proprotein subtilisin/kexin type 9 inhibition provides incremental clinical benefit only when lipoprotein(a) concentration is at least mildly elevated. (ODYSSEY Outcomes: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; NCT01663402).

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  • PCSK9 inhibitors produce a median reduction in Lp(a) percentage, but this reduction does not translate into a decrease in cardiovascular events.

    “Clinical trials have shown a median reduction in Lp(a) percentage with PCSK9 inhibitors, but this reduction does not translate into a decrease in cardiovascular events [14,15].”

    From Residual Cardiovascular Risk: Role of Remnants Cholesterol, Monocyte/HDL Ratio and Lipoprotein Ratios on Personalized Cardiovascular Prevention (2024) · cites this paper as [14]

    The paper supports the first clause: its introduction says PCSK9 inhibitors reduce Lp(a) concentration by 20%–25%. But the Discussion (page not provided) reports that Lp(a) reduction with alirocumab was accompanied by an approximately 30% reduction in major adverse cardiovascular events in patients with LDL-C near 70 mg/dL and elevated Lp(a). It does not establish that Lp(a) lowering alone caused the benefit, but it contradicts the categorical claim that the reduction does not translate into fewer events. (LLM, conf=0.91)

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Schwartz, G. G., Szarek, M., Bittner, V. A., Diaz, R., Goodman, S. G., Jukema, J. W., Landmesser, U., López-Jaramillo, P., Manvelian, G., Pordy, R., Scemama, M., Sinnaeve, P. R., White, H. D., Gabriel Steg, P., Schwartz, G. G., Gabriel Steg, P. H., Bhatt, D. L., Bittner, V. A., Diaz, R., Goodman, S. G., Harrington, R. A., Jukema, J. W., Szarek, M., White, H. D., Zeiher, A. M., Tricoci, P., Roe, M. T., Mahaffey, K. W., Edelberg, J. M., Hanotin, C., Lecorps, G., Moryusef, A., Pordy, R., Sasiela, W. J., Tamby, J.-F., Diaz, R., Aylward, P. E., Drexel, H., Sinnaeve, P., Dilic, M., Lopes, R. D., Gotcheva, N. N., Goodman, S. G., Prieto, J.-C., Yong, H., López-Jaramillo, P., Pećin, I., Reiner, Z., Ostadal, P., Poulsen, S. H., Viigimaa, M., Nieminen, M. S., Danchin, N., Chumburidze, V., Marx, N., Liberopoulos, E., Montenegro Valdovinos, P. C., Tse, H.-F., Kiss, R. G., Xavier, D., Zahger, D., Valgimigli, M., Kimura, T., Kim, H. S., Kim, S.-H., Erglis, A., Laucevicius, A., Kedev, S., Yusoff, K., Ramos López, G. A., Alings, M., White, H. D., Halvorsen, S., Correa Flores, R. M., Sy, R. G., Budaj, A., Morais, J., Dorobantu, M., Karpov, Y., Ristic, A. D., Chua, T., Murin, J., Fras, Z., Dalby, A. J., Tuñón, J., Asita de Silva, H., Hagström, E., Landmesser, U., Müller, C., Chiang, C.-E., Sritara, P., Guneri, S., Parkhomenko, A., Ray, K. K., Moriarty, P. M., Roe, M. T., Vogel, R., Chaitman, B., Kelsey, S. F., Olsson, A. G., Rouleau, J.-L., Simoons, M. L., Alexander, K., Meloni, C., Rosenson, R., Sijbrands, E. J. G., Tricoci, P., Alexander, J. H., Armaganijan, L., Bagai, A., Bahit, M. C., Brennan, J. M., Clifton, S., DeVore, A. D., Deloatch, S., Dickey, S., Dombrowski, K., Ducrocq, G., Eapen, Z., Endsley, P., Eppinger, A., Harrison, R. W., Hess, C. N., Hlatky, M. A., Jordan, J. D., Knowles, J. W., Kolls, B. J., Kong, D. F., Leonardi, S., Lillis, L., Lopes, R. D., Maron, D. J., Mahaffey, K. 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M., Dempsey, M. A., & McClanahan, M. A.
Affiliations
  • Regeneron (United States) (US)
  • St. Michael's Hospital (CA)
  • University of Colorado Anschutz (US)
  • Instituto Cardiovascular de Rosario (AR)
  • Universidad De Santander (CO)
  • State University of New York (US)
  • Universitair Ziekenhuis Leuven (BE)
  • Charité – Universitätsmedizin Berlin (DE)
  • Leiden University Medical Center (NL)
  • University of Alabama at Birmingham (US)
  • Université de Montpellier (FR)
  • Inserm (FR)
  • Auckland City Hospital (NZ)
ORCID
Venue
Journal of the American College of Cardiology
Publisher
Elsevier BV
Published
2021-08
Volume
78
Issue
5
Pages
421-433
ISSN
0735-1097 (ISSN-L)
DOI
10.1016/j.jacc.2021.04.102
PMC
PMC8822604
OpenAlex
W3185845820
Cited by
150
References
7
Citations by year
2026: 23 · 2025: 31 · 2024: 36 · 2023: 30 · 2022: 22 · 2021: 7
FWCI
22.32
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of the American College of Cardiology (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, cc-by-nc-nd)
  • PubMed Central (acceptedVersion, cc-by-nc-nd)
  • Leiden Repository (Leiden University) (submittedVersion, cc-by-nc-nd)
  • Lirias (KU Leuven) (submittedVersion, cc-by-nc-nd)
  • Griffith Research Online (submittedVersion, cc-by-nc-nd)
  • LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, cc-by-nc-nd)
  • National University of Singapore (submittedVersion)
  • Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
  • HAL (submittedVersion)
  • BOA (University of Milano-Bicocca) (submittedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
  • Institutional Repositories DataBase (IRDB) (submittedVersion)
  • RWTH Publications (RWTH Aachen) (submittedVersion)
  • Queen Mary Research Online (Queen Mary University of London) (submittedVersion, cc-by-nc-nd)
Funders
Sanofi
Topics
  • Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Acute Myocardial Infarction Research
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Antiplatelet Therapy and Cardiovascular Diseases
Keywords
lipoprotein(a), PCSK9 inhibition, alirocumab, LDL cholesterol, residual cardiovascular risk, acute coronary syndrome, statin therapy, major adverse cardiovascular events, ODYSSEY OUTCOMES trial, lipid-lowering therapy
MeSH terms
PCSK9 Inhibitors, Aged, Cardiovascular Diseases, Female, Humans, Cholesterol, LDL, Male, Middle Aged, Lipoprotein(a), Acute Coronary Syndrome, Antibodies, Monoclonal, Humanized

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