Effect of Alirocumab on Lipoprotein(a) and Cardiovascular Risk After Acute Coronary Syndrome
Open accessAbstract
BACKGROUND: Lipoprotein(a) concentration is associated with cardiovascular events. Alirocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor, lowers lipoprotein(a) and low-density lipoprotein cholesterol (LDL-C). OBJECTIVES: A pre-specified analysis of the placebo-controlled ODYSSEY Outcomes trial in patients with recent acute coronary syndrome (ACS) determined whether alirocumab-induced changes in lipoprotein(a) and LDL-C independently predicted major adverse cardiovascular events (MACE). METHODS: One to 12 months after ACS, 18,924 patients on high-intensity statin therapy were randomized to alirocumab or placebo and followed for 2.8 years (median). Lipoprotein(a) was measured at randomization and 4 and 12 months thereafter. The primary MACE outcome was coronary heart disease death, nonfatal myocardial infarction, ischemic stroke, or hospitalization for unstable angina. RESULTS: Baseline lipoprotein(a) levels (median: 21.2 mg/dl; interquartile range [IQR]: 6.7 to 59.6 mg/dl) and LDL-C [corrected for cholesterol content in lipoprotein(a)] predicted MACE. Alirocumab reduced lipoprotein(a) by 5.0 mg/dl (IQR: 0 to 13.5 mg/dl), corrected LDL-C by 51.1 mg/dl (IQR: 33.7 to 67.2 mg/dl), and reduced the risk of MACE (hazard ratio [HR]: 0.85; 95% confidence interval [CI]: 0.78 to 0.93). Alirocumab-induced reductions of lipoprotein(a) and corrected LDL-C independently predicted lower risk of MACE, after adjustment for baseline concentrations of both lipoproteins and demographic and clinical characteristics. A 1-mg/dl reduction in lipoprotein(a) with alirocumab was associated with a HR of 0.994 (95% CI: 0.990 to 0.999; p = 0.0081). CONCLUSIONS: Baseline lipoprotein(a) and corrected LDL-C levels and their reductions by alirocumab predicted the risk of MACE after recent ACS. Lipoprotein(a) lowering by alirocumab is an independent contributor to MACE reduction, which suggests that lipoprotein(a) should be an independent treatment target after ACS. (ODYSSEY Outcomes: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; NCT01663402).
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Evolocumab in FOURIER reduced Lp(a) by a median of 26.9% at 48 weeks, and alirocumab in ODYSSEY OUTCOMES showed a median relative reduction of −23% by 4 months.
“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 [26]
For the alirocumab clause, the Abstract reports that ODYSSEY OUTCOMES measured lipoprotein(a) at month 4 and that alirocumab reduced it by a median of 5.0 mg/dl. The Figure 2 discussion (page not available in our copy) says levels were significantly lower at month 4, but our copy does not report the claimed median relative reduction of −23%. The evolocumab clause has separate citations and is not attributed to this source here. (LLM, conf=0.86)
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“This magnitude is in line with findings from injectable PCSK9 therapies: 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 (cid:0) 23% by 4 months[3,26].”
Influential
- Authors
- 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., Harrington, R. A., Jukema, J. W., Loizeau, V., Moriarty, P. M., Moryusef, A., Pordy, R., Roe, M. T., Sinnaeve, P., Tsimikas, S., Vogel, R., White, H. D., Zahger, D., Zeiher, A. M., Steg, P. G., & Schwartz, G. G.
- Affiliations
- University of Alabama at Birmingham (US)
- State University of New York (US)
- Flinders University (AU)
- Brigham and Women's Hospital (US)
- Sanofi (United States) (US)
- University of Ljubljana (SI)
- St. Michael's Hospital (CA)
- Oslo University Hospital (NO)
- Sanofi (France) (FR)
- Stanford University (US)
- Leiden University Medical Center (NL)
- University of Kansas Medical Center (US)
- Regeneron (United States) (US)
- Duke University (US)
- Universitair Ziekenhuis Leuven (BE)
- University of California San Diego (US)
- University of Colorado Anschutz (US)
- Auckland City Hospital (NZ)
- Ben-Gurion University of the Negev (IL)
- Goethe University Frankfurt (DE)
- Corresponding author
- Bittner, Vera A.
- ORCID
- Bittner, Vera A.
- Szarek, Michael
- Aylward, Philip E.
- Bhatt, Deepak L.
- Edelberg, Jay M.
- Fras, Zlatko
- Goodman, Shaun G.
- Halvorsen, Sigrun
- Harrington, Robert A.
- Jukema, J. Wouter
- Moriarty, Patrick M.
- Pordy, Robert
- Roe, Matthew T.
- Sinnaeve, Peter
- Tsimikas, Sotirios
- Vogel, Robert
- White, Harvey D.
- Zahger, Doron
- Zeiher, Andreas M.
- Schwartz, Gregory G.
- Venue
- Journal of the American College of Cardiology
- Publisher
- Elsevier BV
- Published
- 2020-01
- Volume
- 75
- Issue
- 2
- Pages
- 133-144
- ISSN
- 0735-1097 (ISSN-L)
- OpenAlex
- W3000712048
- Cited by
- 572
- References
- 11
- Citations by year
- 2026: 71 · 2025: 93 · 2024: 111 · 2023: 95 · 2022: 65 · 2021: 77 · 2020: 59 · 2019: 1
- FWCI
- 67.63
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of the American College of Cardiology (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
- Leiden Repository (Leiden University) (submittedVersion, cc-by-nc-nd)
- Lirias (submittedVersion, cc-by-nc-nd)
- Lanzhou University Institutional Repository (submittedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Dipòsit Digital de Documents de la UAB (Universitat Autònoma de Barcelona) (submittedVersion, cc-by-nc-nd)
- Dipòsit Digital de la Universitat de Barcelona (Universitat de Barcelona) (submittedVersion, cc-by-nc-nd)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Publication Server of Goethe University Frankfurt am Main (Goethe University Frankfurt) (submittedVersion, cc-by-nc-nd)
- Universidad de Chile (submittedVersion, cc-by-nc-nd)
- Funders
- Sanofi
- Regeneron Pharmaceuticals
- Topics
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Acute Myocardial Infarction Research
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Keywords
- alirocumab, lipoprotein(a), acute coronary syndrome, major adverse cardiovascular events, PCSK9 inhibitors, LDL cholesterol, cardiovascular risk prediction, ODYSSEY OUTCOMES trial, high-intensity statin therapy, coronary artery disease, myocardial infarction, ischemic stroke, unstable angina, lipid-lowering therapy, prognostic factors
- MeSH terms
- Adult, Aged, Cardiovascular Diseases, Female, Humans, Cholesterol, LDL, Male, Middle Aged, Risk Factors, Treatment Outcome, Lipoprotein(a), Acute Coronary Syndrome, Antibodies, Monoclonal, Humanized
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