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STRENGTH Trial: Cardiovascular Outcomes With Omega-3 Carboxylic Acids (Epanova) in Patients With High Vascular Risk and Atherogenic Dyslipidemia

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Author Block: A Lincoff, Cleveland Clinic, Cleveland, OH; Stephen J Nicholls, Victorian Heart Inst, Clayton, Australia; Michelle Garcia, Cleveland Clinic, Cleveland, OH; Dianna Bash, Cleveland Clinic, Shaker Hts, OH; Christie M Ballantyne, Baylor Coll of Med, Houston, TX; Philip Barter, Univ of New South Wales, Sydney, Australia; Michael H DAVIDSON, Univ of Chicago, Highland Park, IL; John Jp Kastelein Jr., Academic Medical Ctr, Amsterdam, Netherlands; Wolfgang Koenig, Deutsches Herzzentrum Muenchen, Munich, Germany; Darren K McGuire, Univ Texas Southwestern Medical Ctr, Dallas, TX; Dariush Mozaffarian, Tufts Univ, Boston, MA; Terje Rolf Pedersen, Oslo Univ Hosp, Oslo, Norway; Paul M Ridker, Brigham and Women's Hosp, Boston, MA; Kausik Ray, Imperial Coll London, London W6 8RP, United Kingdom; Brian Katona, Astra Zeneca LP, Gaithersburg, MD; Anders Himmelmann, AstraZeneca, Molndal, Sweden; Larrye Ellis Loss, Astra Zeneca LP, Gaithersburg, MD; Martin Rensfeldt, AstraZeneca, Molndal, Sweden; Torbjorn Lundstrom, Astrazeneca R&d, Molndal, Sweden; Rahul Agrawal, Astra Zeneca LP, Mölndal, Sweden; Kathy Elizabeth Wolski, Cleveland, Cleveland, OH; Steven E Nissen, Cleveland Clinic, Cleveland, OH; for the STRENGTH Trial Investigators
Disclosure Block: A.Lincoff: Honoraria; Significant; Eli Lilly, Novo Nordisk, Research Grant; Significant; Astra Zeneca, Esperion, AbbVie, CSL, Novartis. D.K.Mcguire: Honoraria; Modest; Metavant, Applied Therapeutics, AstraZeneca, GlaxoSmithKline, Afimmune, Honoraria; Significant; Lilly USA, Boehringer Ingelheim, Merck & Co, Novo Nordisk, Sanofi, Other Research Support; Modest; Merck & Company, Pfizer, Eisai Inc, Esperion, Lilly USA, GlaxoSmith Kline, Janssen, Lexicon, Akebia, AbbVie, Eidos, Arena, Dynavax, Otsuka, CSL Behring, Other Research Support; Significant; AstraZeneca, Sanofi, Boehringer Ingelheim, Novo Nordisk. D.Mozaffarian: Other; Modest; GOED, Nutrition Impact, Pollock Communications, Bunge, Indigo Agriculture, Amarin, Cleveland Clinic Foundation, America’s Test Kitchen, Danone, Omada Health, UpToDate, Other; Significant; Acasti Pharma, Elysium Health, Filcitrine, DayTwo, Research Grant; Significant; National Institutes of Health , Gates Foundation. T.R.Pedersen: Speaker/Speaker's Bureau; Modest; Amgen, Sanofi. P.M.Ridker: Honoraria; Modest; Novartis, J&J, Merck, Sanofi, Amarin, Peter Munk Toronto, Pfizer, Baim Institute, Cleveland Clinic, Honoraria; Significant; Civi Biopharm, Iqvia, Corvidia, Research Grant; Significant; Kowa, Novartis, NHLBI, Amarin. K.Ray: Honoraria; Modest; Amgen, Sanofi, Regeneron, Esperion, Medicines Company, Boehringer Ingelheim, Novo Nordisk, Kowa, Resverlogix, Dr Reddys, Cipla, Algorithm, Zuelling Pharma, Silence Therapeutics, Cerenis, Lilly, Astra Zeneca, Bayer, Akcea, MSD, Novartis, Daiichi Sankyo, Research Grant; Significant; Amgen, Sanofi, Regeneron, MSD, Pfizer, Daiichi Sankyo. B.Katona: Employment; Significant; AstraZeneca, Stock Shareholder; Significant; AstraZeneca. A.Himmelmann: Employment; Significant; AstraZeneca. L.E.Loss: Employment; Significant; AstraZeneca. M.Rensfeldt: Employment; Significant; AstraZeneca. T.Lundstrom: n/a. S.J.Nicholls: Honoraria; Modest; AstraZeneca, Akcea, Eli Lilly, Anthera, Omthera, Merck, Takeda, Resverlogix, Sanofi-Regeneron, CSL Behring, Esperion, Boehringer Ingelheim, Research Grant; Significant; AstraZeneca, Amgen, Anthera, Eli Lilly, Esperion, Novartis, Cerenis, The Medicines Company, Resverlogix, InfraReDx, Roche, Sanofi-Regeneron and LipoScience. R.Agrawal: n/a. K.E.Wolski: None. S.E.Nissen: Research Grant; Significant; Astra Zeneca, Amgen, Pfizer, Novartis, Esperion, Eli Lilly, AbbVie, MyoKardia, Silence Therapeutics, Medtronic. For the strength trial investigators: n/a. M.Garcia: None. D.Bash: n/a. C.M.Ballantyne: Other; Modest; Abbott Diagnostics, Akcea, Amgen, Arrowhead, Astra Zeneca, Esperion, Intercept, Janssen, Matinas BioPharma Inc, Novartis, Novo Nordisk, Regeneron, Corvidia, Pfizer, Other; Significant; Amarin, Denka Seiken, Sanofi-Synthelabo, Research Grant; Significant; Abbott Diagnostic, Akcea, Amgen, Esperion, Novartis, Regeneron, Roche Diagnostic. P.Barter: n/a. M.H.Davidson: Employment; Significant; Corvidia Therapeutics, Speaker/Speaker's Bureau; Significant; A
Background: Considerable interest has focused on the potential for omega-3 fatty acids to lower cardiovascular risk. Observational studies have demonstrated an inverse association between dietary consumption of either fatty fish or omega-3 fatty acids and prospective risk of cardiovascular events. Additional studies have suggested that red blood cell concentrations of either eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) are inversely correlated with cardiovascular risk. Biomarker studies have demonstrated that omega-3 fatty acids exert favorable effects on lipoprotein metabolism and inflammatory, oxidative, thrombotic and arrhythmogenic factors implicated in cardiovascular disease. It remains uncertain whether omega-3 fatty acids reduce cardiovascular risk. Objective: A carboxylic acid formulation of EPA and DHA (omega-3 CA, Epanova™) is administered as a free fatty acid not requiring hydrolysis by pancreatic lipase during intestinal absorption, eliminating the need for co-administration with a high fat diet and resulting in greater bioavailability compared with standard omega-3 ethyl ester formulations. This omega-3 CA has been previously documented to have favorable effects on lipid and inflammatory markers. The STRENGTH Trial (NCT #02104817) assessed the effects of omega-3 CA on cardiovascular outcomes. Design: A double-blind, randomized, multicenter trial (enrollment October 2014 to April 2017; study termination 8 January, 2020) comparing omega-3 CA 4 gm daily (n=6539) with matching corn oil placebo (n=6539) in statin-treated participants with high cardiovascular risk, hypertriglyceridemia (triglyceride levels ≥180 mg/dL and <500 mg/dL) and low levels of HDL-C (HDL cholesterol <42 mg/dL for men or <47 mg/dL for women). Settings and Participants: 13,078 patients were randomized at 675 academic and community hospitals in North America, Europe, South America, Asia, Australia, New Zealand and South Africa. Main Outcome Measures: The primary efficacy measure was a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, coronary revascularization, and hospitalization for unstable angina. Changes in lipid and inflammatory biomarkers, as well as safety and tolerability were evaluated. Results: At a time when 1,384 patients had experienced a primary endpoint event, the independent Data and Safety Monitoring Board recommended termination of the trial for futility. The median patient follow-up was 38.8 (interquartile range 32.8, 45.4) months. Vital status was recorded in 99.8% of patients, and 96.6% of patients had complete follow up of for assessment of the primary endpoint. The final primary results of the trial will be presented.