Effectiveness of icosapent ethyl on first and total cardiovascular events in patients with metabolic syndrome, but without diabetes: REDUCE-IT MetSyn.

Autor:	Miller M; Department of Medicine, Corporal Michael J. Crescenz Veterans Affairs Medical Center and Hospital of the University of Pennsylvania, 3900 Woodland Avenue, Philadelphia, PA 19104-4551, USA., Bhatt DL; Mount Sinai Fuster Heart Hospital, Icahn School of Medicine at Mount Sinai, NewYork, NY, USA., Brinton EA; Utah Lipid Center, Salt Lake City, UT, USA., Jacobson TA; Lipid Clinic and Cardiovascular Risk Reduction Program, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA., Steg PG; Université de Paris, FACT (French Alliance for Cardiovascular Trials), Assistance Publique-Hôpitaux de Paris, Hôpital Bichat, INSERM Unité 1148, Paris, France., Pineda AL; Amarin Pharma, Inc. (Amarin), Bridgewater, NJ, USA., Ketchum SB; Amarin Pharma, Inc. (Amarin), Bridgewater, NJ, USA., Doyle RT Jr; Amarin Pharma, Inc. (Amarin), Bridgewater, NJ, USA., Tardif JC; Montreal Heart Institute, Université de Montréal, Montreal, Canada., Ballantyne CM; Department of Medicine, Baylor College of Medicine, Texas Heart Institute, Houston, TX, USA.
Jazyk:	angličtina
Zdroj:	European heart journal open [Eur Heart J Open] 2023 Nov 12; Vol. 3 (6), pp. oead114. Date of Electronic Publication: 2023 Nov 12 (Print Publication: 2023).
DOI:	10.1093/ehjopen/oead114
Abstrakt:	Aims: Metabolic syndrome (MetSyn) is associated with high risk of cardiovascular (CV) events, irrespective of statin therapy. In the overall REDUCE-IT study of statin-treated patients, icosapent ethyl (IPE) reduced the risk of the primary composite endpoint (CV death, non-fatal myocardial infarction, non-fatal stroke, coronary revascularization, or unstable angina requiring hospitalization) and the key secondary composite endpoint (CV death, non-fatal myocardial infarction, or non-fatal stroke). Methods and Results: REDUCE-IT was an international, double-blind trial that randomized 8179 high CV risk statin-treated patients with controlled LDL cholesterol and elevated triglycerides, to IPE 4 g/day or placebo. The current study evaluated the pre-specified patient subgroup with a history of MetSyn, but without diabetes at baseline. Among patients with MetSyn but without diabetes at baseline ( n = 2866), the majority (99.8%) of this subgroup was secondary prevention patients. Icosapent ethyl use was associated with a 29% relative risk reduction for the first occurrence of the primary composite endpoint [hazard ratio: 0.71; 95% confidence interval (CI): 0.59-0.84; P < 0.0001, absolute risk reduction (ARR) = 5.9%; number needed to treat = 17] and a 41% reduction in total (first plus subsequent) events [rate ratio: 0.59; (95% CI: 0.48-0.72); P < 0.0001] compared with placebo. The risk for the key secondary composite endpoint was reduced by 20% ( P = 0.05) and a 27% reduction in fatal/non-fatal MI ( P = 0.03), 47% reduction in urgent/emergent revascularization ( P < 0.0001), and 58% reduction in hospitalization for unstable angina ( P < 0.0001). Non-statistically significant reductions were observed in cardiac arrest (44%) and sudden cardiac death (34%). Conclusion: In statin-treated patients with a history of MetSyn, IPE significantly reduced the risk of first and total CV events in REDUCE-IT. The large relative and ARRs observed supports IPE as a potential therapeutic consideration for patients with MetSyn at high CV risk. Registration REDUCE-IT ClinicalTrials.gov number: NCT01492361. Competing Interests: Conflict of interest: M.M. served on the Steering Committee for REDUCE-IT and reports consulting or speaking fees from Amarin, 89bio, DalCor Pharmaceuticals, Ionis, and Pfizer. D.L.B. served as the Chair of REDUCE-IT with research funding paid to Brigham and Women’s Hospital and discloses the following relationships—Advisory Board: 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, and Stasys; Board of Directors: American Heart Association New York City, Angiowave (stock options), Bristol Myers Squibb (stock), DRS.LINQ (stock options), and High Enroll (stock); Consultant: Broadview Ventures, Hims, SFJ, and Youngene; 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, and Rutgers University (for the NIH-funded MINT Trial); 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), 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), and Wiley (steering committee); Other: Clinical Cardiology (Deputy Editor); 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 receives any income from this patent); Research Funding: 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, and 89Bio; Royalties: Elsevier (Editor, Braunwald’s Heart Disease); Site Co-Investigator: Abbott, Biotronik, Boston Scientific, CSI, Endotronix, St. Jude Medical (now Abbott), Philips, SpectraWAVE, Svelte, and Vascular Solutions; Trustee: American College of Cardiology; Unfunded Research: FlowCo. E.A.B. served on the steering committees for the REDUCE-IT (Amarin) and PROMINENT (Kowa) trials; received research support from Regeneron; fees as a speaker from Amgen, Amryt, CSL-Behring, and Kaneka; and consulting fees from 89bio, Immunovant, Ionis, Merck, New Amsterdam, and Novo Nordisk. T.A.J. served on the Steering Committee for REDUCE-IT and is a consultant for Amgen, Astra Zeneca, Esperion, Novartis, and Regeneron. P.G.S. reports consulting or speaking fees from Amarin, Amgen, BMS/Myokardia, and Novo-Nordisk; research grants from Amarin, Bayer, Sanofi, and Servier; serving on clinical trials (Steering committee, CEC, DSMB) for Amarin, AstraZeneca, Bayer, Bristol-Myers Squibb, Idorsia, Janssen, Lexicon, Novartis, Pfizer, Sanofi, and Servier and is the Senior Associate Editor at Circulation. A.L.P. is an employee and stockholder of Amarin Pharma, Inc. S.B.K. is an employee and stockholder of Amarin Pharma, Inc. R.T.D. is an employee and stockholder of Amarin Pharma, Inc. J.-C.T. reports grants from Amarin, AstraZeneca, Ceapro, DalCor Pharmaceuticals, Esperion, Ionis, Novartis, Pfizer, and RegenXBio; honoraria from AstraZeneca, DalCor Pharmaceuticals, HLS Pharmaceuticals, Pendopharm, and Pfizer; minor equity interest in DalCor Pharmaceuticals; and patents on pharmacogenomics-guided CETP inhibition and use of colchicine after myocardial infarction. C.M.B. reports grant/research support—all significant and paid to institution, not individual): Abbott Diagnostic, Akcea, Amgen, Arrowhead, Esperion, Ionis, Merck, New Amsterdam, Novartis, Novo Nordisk, Regeneron, Roche Diagnostic, NIH, AHA, and ADA. Consultant—Abbott Diagnostics, Alnylam Pharmaceuticals, Althera, Amarin, Amgen, Arrowhead, Astra Zeneca, Denka Seiken*, Esperion, Genentech, Gilead, Illumina, Ionis, Matinas BioPharma Inc, Merck, New Amsterdam*, Novartis, Novo Nordisk, Pfizer, Regeneron, Roche Diagnostic, NIH, AHA, and ADA. *Significant where noted (>$10 000); remainder modest (<$10 000). (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)
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