Introduction and Objective: PCSK9 inhibition with evolocumab (evo) decreased CV events in pts at high CV risk w/o a prior MI or stroke in VESALIUS-CV. This pre-specified analysis evaluates the efficacy of evo in pts w/ high-risk diabetes mellitus (HR-DM) for prevention of first CV events.Methods: VESALIUS-CV randomized pts w/ LDL-C ≥90mg/dL and atherosclerosis or HR-DM (microvasc. disease, insulin use, or dx ≥10 y) but no prior MI or stroke to evo (140mg Q2W) vs placebo (pbo). The dual primary endpoints were: coronary heart disease death, MI or ischemic stroke (3-P MACE) and the same plus ischemia-driven arterial revascularization (4-P MACE).Results: Of 12,257 pts, 6002 (49%) had HR-DM, of which median age was 66, 50% female, 66% on a high-intensity statin, 24% on SGLT2i or GLP-1RA, and 67% with no qualifying atherosclerosis. After 4.6 y median f/u, evo decreased 3-P MACE by 29% vs pbo in pts w/ HR-DM and 21% in those w/o HR-DM (Pint 0.47; Fig A). Evo decreased 4-P MACE by 21% in HR-DM and 18% in those w/o HR-DM (Pint 0.73; Fig B). Risk of MI was lowered by 35-36% in both subgroups (Pint 0.97). Nominally lower mortality with evo was observed in both subgroups. In HR-DM, findings were consistent for both primary endpoints regardless of qualifying atherosclerosis, baseline LDL-C, statin intensity, and SGLT2i or GLP-1RA use (each Pint >0.05).Conclusion: Evo reduced the rate of CV events in pts with HR-DM, including in those w/o qualifying atherosclerosis or on other cardioprotective agents.
L. Leiter: Advisory Panel; Current; Amgen Canada. Research Support; Current; Amgen Canada. Speaker’s Bureau; Current; Amgen Canada. Research Support; Current; AstraZeneca. Speaker’s Bureau; Current; Boehringer Ingelheim International GmbH. Advisory Panel; Current; Eli Lilly and Company. Research Support; Current; Eli Lilly and Company. Speaker’s Bureau; Current; Eli Lilly and Company. Advisory Panel; Current; HLS Therapeutics Inc. Speaker’s Bureau; Current; HLS Therapeutics Inc. Advisory Panel; Current; Merck & Co., Inc., Novartis Canada. Research Support; Current; Novartis Canada. Speaker’s Bureau; Current; Novartis Canada. Advisory Panel; Current; Novo Nordisk Canada Inc., Regeneron Pharmaceuticals Inc. N. Marston: Research Support; Current; Ionis Pharmaceuticals. Advisory Panel; Current; Ionis Pharmaceuticals. Research Support; Current; Amgen Inc. Advisory Panel; Current; Amgen Inc. Research Support; Current; Marea Therapeutics. Advisory Panel; Current; Arrowhead Pharmaceuticals, Inc. Advisory Panel; Ended; New Amsterdam. Advisory Panel; Current; Radence, Arboretum. G.M. De Ferrari: Advisory Panel; Current; Amgen Inc., Merck Sharp & Dohme Corp. Consultant; Current; UCB, Inc. Advisory Panel; Current; Novartis AG. J.C. Nicolau: Research Support; Current; Amgen Inc., AstraZeneca. Research Support; Ended; Bayer AG, CSL Behring. Research Support; Current; Anthos Therapeutics. Research Support; Ended; Daiichi Sankyo. Research Support; Current; Novo Nordisk, Novartis AG, Ionis Pharmaceuticals, Janssen Pharmaceuticals, Inc. G. Paiva da Silva Lima: Employee; Current; Amgen Inc. Stock/Shareholder; Current; Amgen Inc. A.K. Bhatia: Employee; Current; Amgen Inc. M. Cyrille: Employee; Current; Amgen Inc. J. Park: Other – a member of the TIMI Study Group which has received institutional research grant support through Brigham and Women’s Hospital; Current; Abbott, Abiomed Inc, Amgen Inc., Anthos Therapeutics, ARCA Biopharma Inc, AstraZeneca, Boehringer ingelheim, Cleerly Inc, Daiichi Sankyo, Ionis Pharmaceuticals, Janssen Research & Development, LLC, MedImmune, Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Pfizer Inc., Softcell Medical Limited, The Medicines Company. J. Kuder: Other – I am a member of the TIMI Study Group which has received institutional research grant support through Brigham and Women’s Hospital; Current; Abbott, Amgen Inc., Anthos Therapeutics, AstraZeneca, Boehringer Ingelheim International GmbH, Daiichi Sankyo, Ionis Pharmaceuticals, Janssen Research & Development, LLC, MedImmune, Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Pfizer Inc., Regeneron Pharmaceuticals Inc., Roche Pharmaceuticals, The Medicines Company, Abiomed, Inc., ARCA Biopharma, Inc., Saghmos Therapeutics, Inc., Softcell Medical Limited, Verve Therapeutics, Inc., Zora Biosciences. S. Murphy: Other – Institutional research grant to the TIMI Study Group at Brigham and Women’s Hospital to conduct the CORE trials; Current; Ionis Pharmaceuticals. Other – 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, Cleerly, Inc., Daiichi-Sankyo, Janssen Research and Development, LLC, MedImmune, Merck, Novartis, Pfizer, Regeneron Pharmaceuticals, Inc., Roche,; Current; Many – see Other field. L. Liu: None. H. Wang: Employee; Current; Amgen Inc. A. Dzupina: None. J. Ferreira: Advisory Panel; Current; Amgen Inc. Other – Clinical Trial Steering Committee Member – V2P; Current; Novartis Pharmaceuticals Corporation. Consultant; Ended; Boehringer Ingelheim International GmbH. Other – European Congress of Cardiology invitation; Ended; Menarini Group. Other – Clinical Trial Steering Committee Member – LIBREXIA-AF; Current; Janssen Pharmaceuticals, Inc. Other – Clinical Trial Steering Committee Member – ESSENCE CS9; Ended; Ionis Pharmaceuticals. I. Gouni-Berthold: Speaker’s Bureau; Current; Amgen Inc., Sanofi-Aventis Deutschland GmbH. Advisory Panel; Current; Daiichi Sankyo, Lilly, Novartis Pharma K.K., Menarini Group, Berlin-Chemie AG, Swedish Orphan Biovitrum AB, Arrowhead Pharmaceuticals, Inc. H.K. Jensen: None. N. Sattar: Advisory Panel; Ended; AbbVie Inc. Consultant; Current; Amgen Inc. Advisory Panel; Current; AstraZeneca. Research Support; Current; AstraZeneca. Consultant; Current; Boehringer Ingelheim International GmbH. Research Support; Current; Boehringer Ingelheim International GmbH. Other – Advisory, Consultant and Speaker Honoraria; Current; Eli Lilly and Company. Consultant; Current; Gan & Lee Pharmaceuticals, GlaxoSmithKline plc. Advisory Panel; Ended; Hanmi Pharm. Co., Ltd. Advisory Panel; Current; Kailera. Consultant; Current; Mass Medicines, Menarini Group, Metsera. Other – Advisory, Consultant and Speaker Honoraria; Current; Novo Nordisk. Consultant; Current; Pfizer Inc. Other – Advisory and Consultant; Current; Roche Pharmaceuticals. Other – Speaker Honoraria; Ended; UCB Pharma. Advisory Panel; Current; Verdiva Bio. Advisory Panel; Ended; Regeneron Pharmaceuticals Inc. Consultant; Ended; Carmot Therapeutics, Inc. D. Vinereanu: Research Support; Current; Amgen Inc., Bayer AG, Lilly, Novo Nordisk, Novartis AG, AstraZeneca, Boehringer Ingelheim International GmbH, Ionis Pharmaceuticals, Johnson & Johnson, IQVIA Inc. Speaker’s Bureau; Ended; Pfizer Inc. Research Support; Ended; Celecor. R.P. Giugliano: Research Support; Current; Amgen Inc., Daiichi Sankyo, Ionis Pharmaceuticals, Novartis AG. Other – Honoraria for Academic Lectures / CME programs; Current; Amgen Inc., Daiichi Sankyo. Other – Honoraria for Academic Lectures / CME programs; Ended; Dr. Reddy’s Laboratories Ltd. Other – Honoraria for Academic Lectures / CME programs; Current; Medical Education Resources. Other – Honoraria for Academic Lectures / CME programs; Ended; SUMMEET. Consultant; Current; Daiichi Sankyo, Inventiva Pharma. M.S. Sabatine: Other – Institutional research grant to the TIMI Study Group at Brigham and Women’s Hospital; Consulting; Current; Amgen Inc., AstraZeneca, Boehringer Ingelheim International GmbH. Research Support; Current; Inno Medicine, Ionis Pharmaceuticals, Marea. Other – Institutional research grant to the TIMI Study Group at Brigham and Women’s Hospital; Consulting; Current; Merck & Co., Inc. Research Support; Current; Novartis AG, Pfizer Inc. Consultant; Current; General Medicines. E.A. Bohula: Other – Research Support to Institution; Current; Amgen Inc. Consultant; Current; Amgen Inc. Advisory Panel; Current; Novo Nordisk. Consultant; Current; Medscape. Other – Research Support to Institution; Current; Novartis Pharmaceuticals Corporation, Ionis Pharmaceuticals, AstraZeneca, Pfizer Inc. Research Support; Current; Regeneron Pharmaceuticals Inc. Other – Adjudication committee; Ended; Celecore.
Trial Sponsor: Amgen, Inc
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