Scientific Sessions 2024  /  Lipid Management at Time of ACS  /  Relationship of Oxidized Phospholipids and Lp(a) to Outcomes after Acute Coronary Syndrome: A Post Hoc Analysis of the ODYSSEY OUTCOMES Trial
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American Heart Association

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Final ID: MDP602

Relationship of Oxidized Phospholipids and Lp(a) to Outcomes after Acute Coronary Syndrome: A Post Hoc Analysis of the ODYSSEY OUTCOMES Trial

Abstract Body (Do not enter title and authors here): Background: Oxidized phospholipids (OxPL) are preferentially carried by and contribute to the pro-inflammatory properties of lipoprotein(a) [Lp(a)]. OxPL can be quantitated on all apolipoprotein B-100 containing lipoproteins (OxPL-apoB), a dominant proportion of which are present on Lp(a) particles.

Objectives: To assess the effect of PCSK9 inhibition by alirocumab on plasma levels of OxPL-apoB, and the relationship to Lp(a) and major adverse cardiovascular events (MACE) in patients with a recent acute coronary syndrome (ACS) on optimized statin treatment.

Methods: OxPL-apoB (Diazyme, Inc) and Lp(a) (TinaQuant, Roche Diagnostics) were measured at baseline (1-12 months after ACS) in a subset of participants in the ODYSSEY OUTCOMES trial with samples available at baseline (prior to randomization to alirocumab or placebo, n=11,630) and log2-transformed. Proportional hazards models adjusted for 12 baseline covariates evaluated the association of predictor variables (OxPL-apoB and Lp(a)) with MACE (coronary heart disease death, non-fatal MI, ischemic stroke, and hospitalized unstable angina) and all-cause death, with HRs for doubling of the predictor variable.

Results: Baseline OxPL-apoB correlated with Lp(a) (r=0.68, p<0.001). At 4-months, ALI reduced median (IQR) PBO-corrected OxPL-apoB by 15%, P<0.001. In the placebo group, when analyzed in separate models with multivariable adjustment, pre-randomization OxPL-apoB (HR (95% CI) 1.081 (1.026-1.139), p=0.003) and Lp(a) (HR (95% CI) 1.080 (1.041-1.120), p<0.001) each predicted MACE. However, when OxPL-apoB and Lp(a) were placed in the same model only Lp(a) remained significant (HR (95% CI) 1.069 (1.023, 1.118), p=0.003). In the alirocumab group, neither baseline OxPL-apoB nor Lp(a) predicted MACE in individual or joint models. Baseline high sensitivity C-reactive protein predicted all-cause death, but OxPL-apoB and Lp(a) did not.

Conclusions: In statin-treated patients with recent ACS assigned to placebo, the increased risk of MACE due to elevated OxPL-apoB appears to be mainly driven by their presence on Lp(a). In patients assigned to alirocumab, these variables were not predictive of MACE, suggesting mitigation of OxPL-apoB and Lp(a)-mediated risk by alirocumab.
  • Tsimikas, Sotirios  ( UNIV CALIFORNIA SAN DIEGO , La Jolla , California , United States )
  • Garon, Genevieve  ( Sanofi , Montreal , Quebec , Canada )
  • Chong, Yuan  ( Diazyme Laboratories , Poway , California , United States )
  • Gong, Xiaomin  ( Diazyme Laboratories , Poway , California , United States )
  • Goodman, Shaun  ( ST MICHAELS HOSPITAL , Toronto , Ontario , Canada )
  • Harrington, Robert  ( Weill Cornell Medicine , New York , New York , United States )
  • White, Harvey  ( AUCKLAND CITY HOSPITAL , Auckland , New Zealand )
  • Zeiher, Andreas  ( University of Frankfurt , Frankfurt , Germany )
  • Steg, Philippe  ( Hopital Bichat , Paris , France )
  • Schwartz, Gregory  ( VA EASTERN COLORADO HEALTHCARE SYST , Aurora , Colorado , United States )
  • Szarek, Michael  ( CPC Clinical Research , Aurora , New York , United States )
  • Cobbaert, Christa  ( LUMC , Leiden , Netherlands )
  • Reijnders, Esther  ( Leiden University Medical Center , Leiden , Netherlands )
  • Jukema, J  ( LEIDEN UNIVERSITY MEDICAL CTR , Leiden , Netherlands )
  • Bhatt, Deepak  ( Icahn School of Medicine at Mount Sinai Health System , New York , New York , United States )
  • Bittner, Vera  ( UNIVERSITY ALABAMA BIRMINGHAM , Birmiham , Alabama , United States )
  • Diaz, Rafael  ( Instituto Cardiovascular de Rosario , Rosario , Argentina )
  • Fazio, Sergio  ( Regeneron , Tarrytown , New York , United States )
    • Author Disclosures:
    Sotirios Tsimikas: DO have relevant financial relationships ; Research Funding (PI or named investigator):NIH:Active (exists now) ; Consultant:regeneron:Past (completed) ; Employee:Ionis:Active (exists now) ; Ownership Interest:Kleanthi:Active (exists now) ; Ownership Interest:oxitope:Active (exists now) ; Consultant:Novartis:Active (exists now) | Genevieve Garon: DO have relevant financial relationships ; Employee:Sanofi:Active (exists now) | Yuan Chong: No Answer | Xiaomin Gong: No Answer | Shaun Goodman: DO have relevant financial relationships ; Research Funding (PI or named investigator):Alnylam, Anthos, Bayer, Boehringer Ingelheim, CSL Behring, Idorsia, Novo Nordisk, Sanofi, Regeneron:Active (exists now) ; Consultant:Alnylam, Amgen, Anthos Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, CSL Behring, CYTE Ltd., Daiichi-Sankyo/American Regent, Eli Lilly, Esperion, Ferring Pharmaceuticals, HLS Therapeutics, JAMP Pharma, Merck, Novartis, Pendopharm/Pharmascience, Pfizer, Regeneron, Roche, Sanofi, Servier, Tolmar Pharmaceuticals, Valeo Pharma:Active (exists now) | Robert Harrington: DO have relevant financial relationships ; Researcher:CSL Behring:Active (exists now) ; Other (please indicate in the box next to the company name):Cytokinetics Board of Directors:Active (exists now) ; Advisor:Medscape:Active (exists now) ; Consultant:Basking Bio:Active (exists now) ; Consultant:Foresight Lab:Active (exists now) ; Consultant:Edwards Lifescience:Active (exists now) ; Consultant:Element Science:Active (exists now) ; Consultant:Bridge Bio:Active (exists now) ; Consultant:BMS:Past (completed) ; Consultant:Bitterroot Bio:Active (exists now) ; Consultant:Atropos:Active (exists now) ; Researcher:Janssen:Active (exists now) | Harvey White: DO have relevant financial relationships ; Research Funding (PI or named investigator):National Health Institutes:Active (exists now) ; Consultant:Fees for serving on the Steering committee for Esperion Therapeutics for CLEAR Outcome study:Active (exists now) ; Consultant:Fees for serving on the Steering committee for Esperion Therapeutics for SOLIST and SCORED Studies:Past (completed) ; Consultant:Fees for serving on the Steering committee for CSL Behring for AEGIS II Trial:Active (exists now) ; Consultant:Fees for serving on the Steering committee for DalCor Pharma UK Inc for GenE Study:Active (exists now) ; Consultant:Fees for serving on the Steering committee for Janssen Research and Development LLC for LIBREXIA studies:Active (exists now) ; Advisor:CSL Behring - advsiory board:Past (completed) ; Advisor:VEVRE - Advisory Board:Past (completed) ; Research Funding (PI or named investigator):Janssen Reserch 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):Esperion Therapeutics:Active (exists now) ; Research Funding (PI or named investigator):CSL Behring: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) ; Research Funding (PI or named investigator):Sanofi-Aventis, Regeneron Pharmaceuticals:Active (exists now) | Andreas Zeiher: DO NOT have relevant financial relationships | Philippe Steg: DO have relevant financial relationships ; Consultant:Amgen:Active (exists now) ; Consultant:Idorsia:Active (exists now) ; Consultant:BMS:Active (exists now) ; Consultant:Novo Nordisk:Active (exists now) ; Ownership Interest:Bioquantis:Active (exists now) ; Advisor:Novartis:Active (exists now) ; Consultant:Janssen:Active (exists now) ; Consultant:Amarin:Active (exists now) | Gregory Schwartz: DO have relevant financial relationships ; Research Funding (PI or named investigator):AstraZeneca:Active (exists now) ; Research Funding (PI or named investigator):Silence Therapeutics:Active (exists now) ; Research Funding (PI or named investigator):Sanofi:Active (exists now) | Michael Szarek: DO have relevant financial relationships ; Research Funding (PI or named investigator):Lexicon:Active (exists now) ; Consultant:Silence:Active (exists now) ; Consultant:NewAmsterdam:Active (exists now) ; Advisor:Tourmaline:Active (exists now) ; Consultant:Amarin:Active (exists now) ; Research Funding (PI or named investigator):Sanofi:Active (exists now) | Christa Cobbaert: DO have relevant financial relationships ; Research Funding (PI or named investigator):Roche Diagnostics:Active (exists now) | Esther Reijnders: DO NOT have relevant financial relationships | J Jukema: DO have relevant financial relationships ; Researcher:JW Jukema/his department has received research grants from and/or was speaker (with or without lecture fees) on a.o.(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) | Deepak Bhatt: DO have relevant financial relationships ; Advisor:Angiowave, Bayer, Boehringer Ingelheim, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, High Enroll, Janssen, Level Ex, McKinsey, Medscape Cardiology, Merck, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, Stasys:Active (exists now) ; Other (please indicate in the box next to the company name):Trustee: American College of Cardiology; Unfunded Research: FlowCo:Active (exists now) ; Other (please indicate in the box next to the company name):Site Co-Investigator: Abbott, Biotronik, Boston Scientific, CSI, Endotronix, St. Jude Medical (now Abbott), Philips, SpectraWAVE, Svelte, Vascular Solutions;:Active (exists now) ; Royalties/Patent Beneficiary:Royalties: Elsevier (Editor, Braunwald’s Heart Disease):Active (exists now) ; Researcher:Abbott, Acesion Pharma, Afimmune, Aker Biomarine, Alnylam, Amarin, Amgen, AstraZeneca, Bayer, Beren, Boehringer Ingelheim, Boston Scientific, Bristol-Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, CinCor, Cleerly, CSL Behring, Eisai, Ethicon, Faraday Pharmaceuticals, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Javelin, Lexicon, Lilly, Medtronic, Merck, Moderna, MyoKardia, NirvaMed, Novartis, Novo Nordisk, Otsuka, Owkin, Pfizer, PhaseBio, PLx Pharma, Recardio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, Youngene, 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):Honoraria: Level Ex, Medtelligence/ReachMD (CME steering committees), MJH Life Sciences, Oakstone CME (Course Director, Comprehensive Review of Interventional Cardiology), Piper Sandler, Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and USA national co-leader, funded by Bayer), WebMD (CME steering committees), Wiley (steering committee);: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 (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim; 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), Cowen and Company, Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (Editor in Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor; Associate Editor), K2P (Co-Chair, interdisciplinary curriculum):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 (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), 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 ENVISAGE trial, funded by Daiichi Sankyo; 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:Broadview Ventures, GlaxoSmithKline, Hims, SFJ, Youngene: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: DO have relevant financial relationships ; Researcher:Sanofi:Past (completed) ; Other (please indicate in the box next to the company name):Verve Therapeutics - Member of DSMB:Active (exists now) ; Other (please indicate in the box next to the company name):Eli Lilly - Member of DSMB:Active (exists now) ; Advisor:New Amsterdam Pharma:Active (exists now) ; Research Funding (PI or named investigator):Amgen:Active (exists now) ; Research Funding (PI or named investigator):Novartis:Active (exists now) ; Researcher:DalCor:Past (completed) ; Researcher:Esperion:Past (completed) | Rafael Diaz: No Answer | Sergio Fazio: DO have relevant financial relationships ; Employee:Regeneron Pharmaceuticals, Inc:Active (exists now) ; Individual Stocks/Stock Options:Regeneron Pharmaceuticals, Inc:Active (exists now)
Meeting Info:

Scientific Sessions 2024

2024

Chicago, Illinois

Session Info:

Lipid Management at Time of ACS

Saturday, 11/16/2024 , 02:50PM - 04:15PM

Moderated Digital Poster Session

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