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American Heart Association

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Final ID: MDP24

LDL-C Lowering with Evolocumab and Arterial Aneurysms: Long-Term Analysis from the FOURIER Trial

Abstract Body (Do not enter title and authors here): INTRODUCTION
Arterial aneurysms, particularly abdominal aortic aneurysms (AAA), are life-threatening conditions. Human genetic studies and preclinical mouse models have supported LDL-C reduction through PCSK9i as a strategy to slow the progression of arterial aneurysms.

AIMS
To investigate the rates of arterial aneurysm events among patients randomized to the PCSK9i evolocumab vs. placebo.

METHODS
In FOURIER, 27,564 patients with stable ASCVD and LDL-C ≥70 or non-HDL-C ≥100 mg/dL on statins were randomized to evolocumab vs. placebo and followed for a median of 2.2 years. 6,635 patients entered the open-label extension period and received evolocumab for 5 years, irrespective of initial assignment. The primary endpoint of this analysis was any aneurysm event, defined as diagnosis, progression, or intervention related to an arterial aneurysm. Adverse events were reported by the local site and potential aneurysm events were centrally identified by blinded investigators. Procedure-related pseudoaneurysms were excluded. A Cox model, adjusted for randomization stratification factors and an indicator for inclusion in the open-label cohort, was used to compare randomized groups throughout the two trial periods.

RESULTS
A total of 236 patients had aneurysm events (58% AAA) during follow-up. Patients who had aneurysm events were older (median age 67 vs. 63 yrs), more likely to be male (86% vs. 75%) and have a history of PAD (21% vs. 13%). Patients randomized to evolocumab had significantly lower rates of aneurysm events during follow-up (HR 0.77 [0.59–0.99]; p=0.041) (Figure). The association between randomization to evolocumab and fewer aneurysm events was consistent for both AAA (HR 0.78 [0.56–1.09]) and non-AAA (HR 0.81 [0.55–1.18]).

CONCLUSION
In patients with stable ASCVD on optimized statin therapy, early initiation of long-term evolocumab was associated with fewer arterial aneurysm events compared with delayed initiation. These data support earlier intensive LDL-C reduction with PCSK9i as a promising strategy to prevent the formation and progression of arterial aneurysms, including AAA.
  • Gaba, Prakriti  ( Brigham , Boston , Massachusetts , United States )
  • Keech, Anthony  ( NHMRC CLINICAL TRIALS CENTRE , Camperdown Sydney , New South Wales , Australia )
  • Sabatine, Marc  ( TIMI Study Group, Brigham & Women's Hospital , Boston , Massachusetts , United States )
  • Marston, Nicholas  ( Brigham And Womens Hospital , Boston , Massachusetts , United States )
  • Bergmark, Brian  ( Brigham and Womens Hospital , Boston , Massachusetts , United States )
  • Zimerman, Andre  ( Brigham and Women's Hospital , Boston , Massachusetts , United States )
  • O'donoghue, Michelle  ( TIMI Study Group , Boston , Massachusetts , United States )
  • Giugliano, Robert  ( TIMI Study Group , Boston , Massachusetts , United States )
  • Murphy, Sabina  ( TIMI Study Group, Brigham & Women's Hospital , Boston , Massachusetts , United States )
  • Kuder, Julia  ( TIMI Study Group , Boston , Massachusetts , United States )
  • Monsalvo, Maria Laura  ( AMGEN INC , Westlake Village , California , United States )
  • Flores-arredondo, Jose  ( AMGEN Inc. , Thousand Oaks , California , United States )
  • Atar, Dan  ( OSLO UNIVERSITY HOSPITAL ULLEVAL , Oslo , Norway )
  • Author Disclosures:
    Prakriti Gaba: DO NOT have relevant financial relationships | Anthony Keech: No Answer | Marc Sabatine: DO have relevant financial relationships ; Research Funding (PI or named investigator):Amgen:Active (exists now) ; Research Funding (PI or named investigator):Pfizer:Active (exists now) ; Research Funding (PI or named investigator):Novartis:Active (exists now) ; Research Funding (PI or named investigator):Merck:Active (exists now) ; Research Funding (PI or named investigator):Ionis:Active (exists now) ; Consultant:AstraZeneca:Active (exists now) ; Individual Stocks/Stock Options:AstraZeneca:Active (exists now) ; Consultant:Anthos:Active (exists now) ; Research Funding (PI or named investigator):Anthos:Active (exists now) ; Consultant:Amgen:Active (exists now) | Nicholas Marston: DO have relevant financial relationships ; Speaker:Amgen:Past (completed) ; Researcher:Pfizer:Past (completed) ; Consultant:NewAmsterdam:Past (completed) ; Researcher:Marea:Active (exists now) ; Researcher:Ionis:Active (exists now) ; Researcher:Amgen:Active (exists now) | Brian Bergmark: DO have relevant financial relationships ; Consultant:Abbott, Abiomed, Bain Life Sciences, Endovascular Engineering, Bolt, Shockwave, Boston Scientific:Active (exists now) ; Research Funding (PI or named investigator):Ionis, Pfizer, Amgen, AstraZeneca, Abbott, Inari:Active (exists now) | Andre Zimerman: DO NOT have relevant financial relationships | Michelle O'Donoghue: DO have relevant financial relationships ; Consultant:Janssen:Active (exists now) ; Consultant:NovoNordisk:Active (exists now) ; Consultant:Verve:Active (exists now) ; Consultant:AstraZeneca:Active (exists now) ; Consultant:Novartis:Active (exists now) ; Consultant:Amgen:Active (exists now) ; Researcher:AstraZeneca:Active (exists now) ; Researcher:Marea:Active (exists now) ; Researcher:Novartis:Active (exists now) ; Researcher:Amgen:Active (exists now) | Robert Giugliano: No Answer | Sabina Murphy: DO have relevant financial relationships ; Other (please indicate in the box next to the company name):I am a member of the TIMI Study Group which has received institutional research grant support through Brigham and Women’s Hospital from Abbott, Abiomed, Inc., Amgen, Anthos Therapeutics, ARCA Biopharma, Inc., AstraZeneca, Boehringer Ingelheim, Daiichi-Sankyo, Ionis Pharmaceuticals, Inc., Janssen Research and Development, LLC, MedImmune, Merck, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., Roche, Saghmos Therapeutics, Inc., Siemens Healthcare Diagnostics, Inc., Softcell Medical Limited, The Medicines Company, Verve Therapeutics, Inc., Zora Biosciences:Active (exists now) | Julia Kuder: DO NOT have relevant financial relationships | Maria Laura Monsalvo: DO have relevant financial relationships ; Employee:Amgen Inc:Active (exists now) | Jose Flores-Arredondo: DO have relevant financial relationships ; Employee:AMGEN:Active (exists now) | Dan Atar: DO have relevant financial relationships ; Speaker:Amgen, Amarin, AstraZeneca, Bayer, Boehringer-Ingelheim, BMS, GSK, MSD, Novartis, NovoNordisk, Pfizer, Pharmacosmos, Philips, Roche-Diagnostics, Sanofi, Takeda, Vifor.:Past (completed) ; Research Funding (PI or named investigator):Grant support (to the Institution): BMS/Pfizer, Medtronic, Bayer, Roche-Diagnostics.:Active (exists now)
Meeting Info:

Scientific Sessions 2024

2024

Chicago, Illinois

Session Info:

Clinical and Translational Studies of Lipoproteins and Lipids in Vascular Diseases

Saturday, 11/16/2024 , 12:50PM - 02:15PM

Moderated Digital Poster Session

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