4-LB: Substantial Cardiovascular Benefit from Icosapent Ethyl in Patients with Diabetes: REDUCE-IT DIABETES (2020)

Background: Statin-treated patients with diabetes mellitus (DM) are at high cardiovascular (CV) risk. Methods: In REDUCE-IT, icosapent ethyl (IPE; 4 g/day) reduced CV risk vs. placebo in statin-treated patients with either DM plus risk factors or established CV disease. The primary endpoint was CV death, myocardial infarction (MI), stroke, coronary revascularization, or unstable angina. The key secondary endpoint was CV death, MI, or stroke. Key DM analyses were prespecified. Results: 58.5% of patients had DM; 91.0% on ≥1 DM medication, 49.5% on ≥2. IPE reduced primary (Figure) and key secondary first and total (first plus recurrent) events. Patients with and without DM both showed substantial benefits, but patients with DM had 1.5-fold greater rates of the primary endpoint in the placebo group, and a 7% absolute risk reduction in first and a 12.7% reduction in total events (both p&amp;lt;0.001) with IPE. Efficacy and safety were generally consistent with the full study, including reductions in secondary and tertiary endpoints and subgroups, and increases in atrial fibrillation/flutter (3.5% vs. 2.2%; p=0.13) and bleeding (13.1% vs. 10.9%; p=0.02); serious bleeding was not significant (3.2% vs. 2.5%). Fasting glucose and HbA1c were stable. Conclusion: IPE 4 g/day provides robust CV benefits in statin-treated patients with DM, with large relative and absolute risk reductions in both first and total CV events. Disclosure D.L. Bhatt: Research Support; Self; Abbott, Afimmune, Amarin Corporation, Amgen, AstraZeneca, Bayer Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Cardax, Chiesi USA, Inc., CSL Behring, Ferring Pharmaceuticals, Fractyl Laboratories, Inc., Idorsia, Ironwood Pharmaceuticals, Ischemix, Lexicon Pharmaceuticals, Inc., Lilly Diabetes, Medtronic, Pfizer Inc., PhaseBio Pharmaceuticals, Inc., PLx Pharma Inc., Regeneron Pharmaceuticals, Roche Pharma, Sanofi-Aventis, Synaptic. E.A. Brinton: Consultant; Self; Esperion Therapeutics, Inc., Medicines Company, Regeneron Pharmaceuticals. Speaker’s Bureau; Self; Amarin Corporation, Amgen, Esperion Therapeutics, Inc. Other Relationship; Self; Amarin Corporation, Kowa Pharmaceuticals America, Inc. M. Miller: Consultant; Self; Amarin Corporation. P.G. Steg: Consultant; Self; Amgen, AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb, Idorsia, Mylan, Novartis AG, Pfizer Inc., Sanofi, Servier. Research Support; Self; Amarin Corporation. Speaker’s Bureau; Self; Novo Nordisk A/S. T.A. Jacobson: Consultant; Self; Esperion Therapeutics, Inc., Regeneron Pharmaceuticals, Sanofi US. Other Relationship; Self; Amarin Corporation. S.B. Ketchum: Other Relationship; Self; Amarin Corporation. R.T. Doyle: Other Relationship; Self; Amarin Corporation. R.A. Juliano: Other Relationship; Self; Amarin Corporation. L. Jiao: Other Relationship; Self; Amarin Corporation. C. Granowitz: Other Relationship; Self; Amarin Corporation. O. Ganda: Consultant; Self; Amarin Corporation. Other Relationship; Self; Novo Nordisk A/S. F.K. Welty: Other Relationship; Self; Boehringer Ingelheim International GmbH. R.S. Busch: Research Support; Self; Amarin Corporation, Bayer AG, Lexicon Pharmaceuticals, Inc., Lilly Diabetes, Novo Nordisk Inc. Speaker’s Bureau; Self; Amarin Corporation, Amgen, Esperion Therapeutics, Inc., Novo Nordisk Inc., Sanofi US. A.C. Goldberg: Advisory Panel; Self; Akcea Therapeutics, Esperion Therapeutics, Inc., Novartis Pharmaceuticals Corporation, Regeneron Pharmaceuticals, Sanofi-Aventis. Research Support; Self; Akcea Therapeutics, Amarin Corporation, Amgen, Ionis Pharmaceuticals, Inc., Novartis Pharmaceuticals Corporation, Pfizer Inc., Regeneron Pharmaceuticals, Sanofi-Aventis. Other Relationship; Self; Merck &amp; Co., Inc. D.M. Herrington: None. M. Budoff: Research Support; Self; Amarin Corporation, General Electric. Speaker’s Bureau; Self; Amarin Corporation. J. Tardif: Research Support; Self; Esperion Therapeutics, Inc., Ionis Pharmaceuticals, Inc., REGENXBIO Inc., Sanofi, Servier. Other Relationship; Self; Amarin Corporation, AstraZeneca, DalCor Pharmaceuticals. C.M. Ballantyne: Consultant; Self; Abbott, Akcea Therapeutics, Amarin Corporation, Amgen, Arrowhead Pharmaceuticals, Inc., AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Corvidia, Denka-Seiken Co., Ltd., Esperion Therapeutics, Inc., Gilead Sciences, Inc., Janssen Pharmaceuticals, Inc., Matinas BioPharma, Merck &amp; Co., Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Regeneron Pharmaceuticals, Roche Diagnostic USA, Sanofi. Research Support; Self; Abbott, Akcea Therapeutics, Amgen, Esperion Therapeutics, Inc., Novartis Pharmaceuticals Corporation, Regeneron Pharmaceuticals, Roche Diagnostic USA. Funding Amarin Pharma Inc