1. An "Inclisiran First" Strategy vs Usual Care in Patients With Atherosclerotic Cardiovascular Disease.
- Author
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Koren MJ, Rodriguez F, East C, Toth PP, Watwe V, Abbas CA, Sarwat S, Kleeman K, Kumar B, Ali Y, and Jaffrani N
- Subjects
- Aged, Female, Humans, Male, Middle Aged, Oligonucleotides therapeutic use, Prospective Studies, Treatment Outcome, Atherosclerosis drug therapy, Cholesterol, LDL blood, Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use
- Abstract
Background: Most patients with atherosclerotic cardiovascular disease fail to achieve guideline-directed low-density lipoprotein cholesterol (LDL-C) goals. Twice-yearly inclisiran lowers LDL-C by ∼50% when added to statins., Objectives: This study evaluated the effectiveness of an "inclisiran first" implementation strategy (adding inclisiran immediately upon failure to reach LDL-C <70 mg/dL despite receiving maximally tolerated statins) vs representative usual care in U.S. patients with atherosclerotic cardiovascular disease., Methods: VICTORION-INITIATE, a prospective, pragmatically designed trial, randomized patients 1:1 to inclisiran (284 mg at days 0, 90, and 270) plus usual care (lipid management at treating physician's discretion) vs usual care alone. Primary endpoints were percentage change in LDL-C from baseline and statin discontinuation rates., Results: We randomized 450 patients (30.9% women, 12.4% Black, 15.3% Hispanic); mean baseline LDL-C was 97.4 mg/dL. The "inclisiran first" strategy led to significantly greater reductions in LDL-C from baseline to day 330 vs usual care (60.0% vs 7.0%; P < 0.001). Statin discontinuation rates with "inclisiran first" (6.0%) were noninferior vs usual care (16.7%). More "inclisiran first" patients achieved LDL-C goals vs usual care (<70 mg/dL: 81.8% vs 22.2%; <55 mg/dL: 71.6% vs 8.9%; P < 0.001). Treatment-emergent adverse event (TEAE) and serious TEAE rates compared similarly between treatment strategies (62.8% vs 53.7% and 11.5% vs 13.4%, respectively). Injection-site TEAEs and TEAEs causing treatment withdrawal occurred more commonly with "inclisiran first" than usual care (10.3% vs 0.0% and 2.6% vs 0.0%, respectively)., Conclusions: An "inclisiran first" implementation strategy led to greater LDL-C lowering compared with usual care without discouraging statin use or raising new safety concerns. (A Randomized, Multicenter, Open-label Trial Comparing the Effectiveness of an "Inclisiran First" Implementation Strategy to Usual Care on LDL Cholesterol [LDL-C] in Patients With Atherosclerotic Cardiovascular Disease and Elevated LDL-C [≥70 mg/dL] Despite Receiving Maximally Tolerated Statin Therapy [VICTORION-INITIATE]; NCT04929249)., Competing Interests: Funding Support and Author Disclosures VICTORION-INITIATE was funded by Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA. Dr Koren is an employee of a company that received PI fees for his participation in the Novartis VICTORION-INITIATE trial and that has received study grants and consulting fees from multiple manufacturers of PCSK9 inhibitors and other treatments for lipid disorders. Dr Rodriguez has received consulting fees from Healthpals, Novartis, Novo Nordisk (CEC), Edwards, Kento Health, Inclusive Health, and Arrowhead Pharmaceuticals; and has equity in Carta Healthcare. Dr East has received research support from Amgen, Bard, Bio89, Gore, Lilly, Medtronic, Merit Medical, Mission Therapeutics, Novartis, Novo Nordisk, Penumbra, and ReCOR Medical. Dr Toth has received Speaker Bureau fees from Amgen; and has served as a consultant for Novartis. Dr Watwe has received research funding from Novartis and Novo Nordisk. Dr Abbas is employed by Novartis. Drs Sarwat, Kleeman, Kumar, and Ali are employees of Novartis Pharmaceuticals Corporation. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
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