Scientific Sessions 2025  /  Cholesterol Chronicles: Lipid Markers and Cardiovascular Disease  /  Small, Dense LDL-C and Conventional LDL-C Similarly Predict Cardiovascular Risk and Benefit of Alirocumab in Statin-Treated Patients With Recent Acute Coronary Syndrome
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American Heart Association

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Final ID: MP1497

Small, Dense LDL-C and Conventional LDL-C Similarly Predict Cardiovascular Risk and Benefit of Alirocumab in Statin-Treated Patients With Recent Acute Coronary Syndrome

Abstract Body (Do not enter title and authors here): Introduction: Small, dense low-density lipoprotein (sdLDL) particles are believed to be a highly atherogenic subfraction of LDL due to prolonged residence time in circulation, greater adherence to and penetration of vascular endothelium, and higher susceptibility to oxidation. Automated biochemical measurement of sdLDL cholesterol (sdLDL-C) has demonstrated good fidelity to gold standard gradient ultracentrifugation or NMR spectroscopy. We evaluated the relationship of sdLDL-C and conventional LDL-C to risk of major adverse cardiovascular events (MACE) and treatment benefit of alirocumab in patients with recent acute coronary syndrome (ACS) receiving high-intensity or maximum-tolerated statin treatment.
Methods: The analysis included 11,837 participants in the ODYSSEY OUTCOMES trial (NCT01663402) with recent ACS and LDL-C ≥70 mg/dL despite optimized statin treatment. At baseline prior to randomized treatment with the PCSK9 monoclonal antibody alirocumab (N=5917) or placebo (N=5920), sdLDL-C was measured using the Denka (Nigata, Japan) method on a Roche cobas autoanalyzer and LDL-C was calculated with the Friedewald formula. In the placebo group, natural cubic splines depicted the relationships of sdLDL-C, LDL-C, and their ratio to the risk of MACE (CV death, non-fatal myocardial infarction or ischemic stroke, hospitalization for unstable angina, and ischemia-driven coronary revascularization) and treatment hazard ratio (HR: alirocumab/placebo) as a function of sdLDL-C and LDL-C.
Results: In Figure Panel A, the risk of MACE in the placebo group increased with concentrations of baseline sdLDL-C and LDL-C, with nearly superimposable splines. In Panel B, the relationship of sdLDL-C/LDL-C to risk of MACE in the placebo group (adjusted for LDL-C) showed no evidence of greater risk with greater sdLDL-C fraction. Overall, alirocumab reduced the risk of MACE (HR 0.87, 95% CI 0.79, 0.95). Panel C shows that the treatment HR did not vary significantly across the range of either LDL-C or sdLDL-C.
Conclusion: In patients with recent ACS and LDL-C ≥70 mg/dL on optimized statin treatment, sdLDL-C and conventional LDL-C similarly predict risk of MACE and benefit of treatment with alirocumab. Measurement of sdLDL-C does not appear to provide additional prognostic or predictive information.
  • Schwartz, Gregory  ( University of Colorado School of Medicine , Aurora , Colorado , United States )
  • Szarek, Michael  ( CPC Clinical Research , Aurora , Colorado , United States )
  • Cobbaert, Christa  ( Leiden University Medical Center , Leiden , Netherlands )
  • Ruhaak, Lucia Renee  ( Leiden University Medical Center , Leiden , Netherlands )
  • Schwertfeger, Markus  ( Roche Diagnostics International Ltd , Rotkreuz , Switzerland )
  • Bhatt, Deepak  ( Mount Sinai Fuster Heart Hospital , New York , New York , United States )
  • Bittner, Vera  ( University of Alabama at Birmingham , Birmingham , Alabama , United States )
  • Goodman, Shaun  ( St Michaels Hospital , Toronto , Ontario , Canada )
  • Harrington, Robert  ( Weill Cornell Medicine , New York , New York , United States )
  • Reijnders, Esther  ( Leiden University Medical Center , Leiden , Netherlands )
  • Romijn, Fred  ( Leiden University Medical Center , Leiden , Netherlands )
  • Stevanovic, Irena  ( Sanofi , Paris , France )
  • Tavori, Hagai  ( Sanofi , Yakum , Israel )
  • Van Neer, Nicolaas  ( Leiden University Medical Center , Leiden , Netherlands )
  • White, Harvey  ( Auckland City Hospital , Auckland , New Zealand )
  • Jukema, J  ( Leiden University Medical Center , Leiden , Netherlands )
    • Author Disclosures:
    Gregory Schwartz: DO have relevant financial relationships ; Researcher:AstraZeneca:Active (exists now) ; Researcher:Silence Therapeutics:Active (exists now) ; Researcher:Sanofi:Active (exists now) | Esther Reijnders: DO NOT have relevant financial relationships | Fred Romijn: No Answer | Irena Stevanovic: DO have relevant financial relationships ; Employee:Sanofi:Active (exists now) | Hagai Tavori: No Answer | Nicolaas van Neer: No Answer | Harvey White: DO have relevant financial relationships ; Research Funding (PI or named investigator):Sanofi-Aventis, Regeneron Pharmaceuticals:Active (exists now) ; Speaker:Merck Sharp & Dohme (New Zealand) Ltd:Active (exists now) ; Advisor:VEVRE:Past (completed) ; Advisor:NHMRC Clinical Trials Centre, the University of Sydney:Active (exists now) ; Research Funding (PI or named investigator):Merck Sharp & Dohme (New Zealand) Ltd:Active (exists now) ; Research Funding (PI or named investigator):Janssen Research and Development LLC:Active (exists now) ; Research Funding (PI or named investigator):Sanofi Aventis Australia Pty Ltd:Active (exists now) ; Research Funding (PI or named investigator):Omthera Pharmaceuticals:Active (exists now) ; Research Funding (PI or named investigator):Esperion Therapeutics,:Active (exists now) ; Research Funding (PI or named investigator):National Health Institutes:Active (exists now) ; Research Funding (PI or named investigator):DalCor Pharma UK, Inc :Active (exists now) ; Research Funding (PI or named investigator):American Regent:Active (exists now) | J Jukema: DO have relevant financial relationships ; Researcher:JW Jukema/his department has received research grants from and/or was speaker (CME accredited) meetings sponsored/supported by Abbott, Amarin, Amgen, Athera,, Biotronik, Boston Scientific, Dalcor, Daiichi Sankyo, Edwards Lifesciences, GE Healthcare Johnson and Johnson, Lilly, Medtronic, Merck-Schering-Plough, Novartis, Novo Nordisk, Pfizer, Roche, Sanofi Aventis,Shockwave Medical, the Netherlands Heart Foundation, CardioVascular Research the Netherlands (CVON), the Netherlands Heart Institute and the European Community Framework KP7 Programme.:Active (exists now) | Michael Szarek: No Answer | Christa Cobbaert: DO have relevant financial relationships ; Research Funding (PI or named investigator):Roche Diagnostics:Active (exists now) | Lucia Renee Ruhaak: DO NOT have relevant financial relationships | Markus Schwertfeger: DO have relevant financial relationships ; Employee:Roche Diagnostics International Ltd.:Active (exists now) | Deepak Bhatt: DO have relevant financial relationships ; Advisor:Advisory Board: Angiowave, Antlia Bioscience, Bayer, Boehringer Ingelheim, CellProthera, Cereno Scientific, E-Star Biotech, High Enroll, Janssen, Level Ex, McKinsey, Medscape Cardiology, Merck, NirvaMed, Novo Nordisk, Repair Biotechnologies, Stasys, Tourmaline Bio:Active (exists now) ; Individual Stocks/Stock Options:Angiowave (stock options), Bristol Myers Squibb (stock), DRS.LINQ (stock options), High Enroll (stock);:Active (exists now) ; Other (please indicate in the box next to the company name):Site Co-Investigator: Cleerly.:Active (exists now) ; Royalties/Patent Beneficiary:Royalties: Elsevier (Editor, Braunwald’s Heart Disease);:Active (exists now) ; Researcher:Research Funding: Abbott, Acesion Pharma, Afimmune, Alnylam, Amarin, Amgen, AstraZeneca, Atricure, Bayer, Boehringer Ingelheim, Boston Scientific, CellProthera, Cereno Scientific, Chiesi, Cleerly, CSL Behring, Faraday Pharmaceuticals, Fractyl, Idorsia, Janssen, Javelin, Lexicon, Lilly, Medtronic, Merck, MiRUS, Moderna, Novartis, Novo Nordisk, Pfizer, PhaseBio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, 89Bio;:Active (exists now) ; Royalties/Patent Beneficiary:Patent: Sotagliflozin (named on a patent for sotagliflozin assigned to Brigham and Women's Hospital who assigned to Lexicon; neither I nor Brigham and Women's Hospital receive any income from this patent);:Active (exists now) ; Other (please indicate in the box next to the company name):Other: Clinical Cardiology (Deputy Editor); Progress in Cardiovascular Diseases (Deputy Editor);:Active (exists now) ; Other (please indicate in the box next to the company name):Honoraria: American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org; Chair, ACC Accreditation Oversight Committee), Arnold and Porter law firm (work related to Sanofi/Bristol-Myers Squibb clopidogrel litigation), Baim Institute for Clinical Research (AEGIS-II executive committee funded by CSL Behring), Belvoir Publications (Editor in Chief, Harvard Heart Letter), Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), CSL Behring (AHA lecture), Duke Clinical Research Institute, Engage Health Media, HMP Global (Editor in Chief, Journal of Invasive Cardiology), Medtelligence/ReachMD (CME steering committees), MJH Life Sciences, Oakstone CME (Course Director, Comprehensive Review of Interventional Cardiology), Philips (Becker's Webinar on AI), Population Health Research Institute, WebMD (CME steering committees), Wiley (steering committee);:Active (exists now) ; Other (please indicate in the box next to the company name):Data Monitoring Committees: Acesion Pharma, Assistance Publique-Hôpitaux de Paris, Baim Institute for Clinical Research, Boston Scientific (Chair, PEITHO trial), Cleveland Clinic, Contego Medical (Chair, PERFORMANCE 2), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ABILITY-DM trial, funded by Concept Medical; for ALLAY-HF, funded by Alleviant Medical), Novartis, Population Health Research Institute; Rutgers University (for the NIH-funded MINT Trial);:Active (exists now) ; Consultant:Consultant: Alnylam, Altimmune, Broadview Ventures, Corcept Therapeutics, Corsera, GlaxoSmithKline, Hims, SERB, SFJ, Summa Therapeutics, Worldwide Clinical Trials:Active (exists now) ; Other (please indicate in the box next to the company name):Board of Directors: American Heart Association New York City, Angiowave (stock options), Bristol Myers Squibb (stock), DRS.LINQ (stock options), High Enroll (stock);:Active (exists now) | Vera Bittner: No Answer | Shaun Goodman: DO have relevant financial relationships ; Consultant:Merck:Active (exists now) ; Researcher:Novartis:Active (exists now) ; Researcher:Idorsia/Viatris:Active (exists now) ; Consultant:HLS Therapeutics:Active (exists now) ; Researcher:Eli Lilly:Active (exists now) ; Researcher:Daiichi-Sankyo/American Regent:Past (completed) ; Researcher:CYTE Ltd.:Active (exists now) ; Researcher:CSL Behring:Active (exists now) ; Consultant:Bristol Myers Squibb:Active (exists now) ; Researcher:Boehringer Ingelheim:Past (completed) ; Researcher:Bayer:Past (completed) ; Researcher:Sanofi/Regeneron:Active (exists now) ; Researcher:Anthos Therapeutics:Active (exists now) ; Researcher:Amgen:Active (exists now) ; Researcher:Alnylam:Active (exists now) | Robert Harrington: DO have relevant financial relationships ; Research Funding (PI or named investigator):Janssen:Active (exists now) ; Consultant:Medscape:Active (exists now) ; Consultant:Heart Beam:Active (exists now) ; Consultant:Element Science:Active (exists now) ; Consultant:Cosera Health:Active (exists now) ; Consultant:Bitterroot Bio:Active (exists now) ; Consultant:Basking Bioscience:Active (exists now) ; Consultant:Atropos Health:Active (exists now) ; Other (please indicate in the box next to the company name):Merck DSMB Chair:Active (exists now) ; Research Funding (PI or named investigator):Edwards:Active (exists now)
Meeting Info:

Scientific Sessions 2025

2025

New Orleans, Louisiana

Session Info:

Cholesterol Chronicles: Lipid Markers and Cardiovascular Disease

Sunday, 11/09/2025 , 11:50AM - 01:05PM

Moderated Digital Poster Session

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