Alirocumab and Cardiovascular Outcomes in Patients with Acute Coronary Syndrome (ACS) and Diabetes—Prespecified Analyses of ODYSSEY OUTCOMES
Authors: RAY KAUSIK K. , COLHOUN HELEN , SZAREK MICHAEL , BACCARA-DINET MARIE , BHATT DEEPAK L. , BITTNER VERA , BUDAJ ANDRZEJ J. , DIAZ RAFAEL , GOODMAN SHAUN G. , HANOTIN CORINNE G. , WOUTER JUKEMA J. , LOIZEAU VIRGINIE , LOPES RENATO D. , MORYUSEF ANGELE , PORDY ROBERT , RISTIC ARSEN D. , ROE MATTHEW , TUÑÓN JOSÉ , WHITE HARVEY D. , SCHWARTZ GREGORY G. , STEG PHILIPPE G. ,   ODYSSEY OUTCOMES INVESTIGATORS
Published: June 2018

Background: People with diabetes and recent ACS are at higher risk for ischemic CV events and derive greater benefit from intensive lipid-lowering therapy than those without diabetes. Effect of PCSK9 inhibition in patients with recent ACS and diabetes is unknown.
Methods: Alirocumab (ALI) is a fully human monoclonal antibody to PCSK9. In ODYSSEY OUTCOMES, 18,924 patients with recent ACS and LDL-C≥70mg/dL on a maximum-tolerated dose of atorvastatin or rosuvastatin were randomly assigned to ALI 75mg or placebo SC every 2 weeks. ALI blindly increased to 150mg or decreased to placebo to achieve an LDL-C of 25-50mg/dL. Primary efficacy endpoint was time to first MACE: CHD death, nonfatal MI, ischemic stroke or hospitalization for unstable angina. This prespecified analysis reports efficacy and safety by baseline glucometabolic status, including new-onset diabetes (NOD).
Results: Table reports incidence of MACE by assigned treatment and baseline glucometabolic status. Overall ALI reduced MACE, without evidence of effect modification by baseline glucometabolic status: a greater absolute risk reduction was observed with ALI in those with diabetes. NOD was not increased with ALI.
Conclusion: Patients with recent ACS and diabetes derived greater absolute benefit from ALI added to maximum-tolerated statin. No increase in NOD was seen with ALI (NCT01663402).CategoryN (% of cohort)ARRHazard ratio (95% CI)PinteractionMACE cumulative incidenceAlirocumab n/N (%)Placebo n/N (%)All subjects18,924 (100)903/9462 (9.5)1052/9462 (11.1)1.60.85 (0.78, 0.93)NADiabetes5444 (28.8)380/2693 (14.1)452/2751 (16.4)2.30.84 (0.74, 0.97)0.98 Prediabetes8246 (43.6)331/4130 (8.0)380/4116 (9.2)1.20.86 (0.74, 1.00)Normoglycemia5234 (27.7)192/2639 (7.3)220/2595 (8.5)1.20.85 (0.70, 1.03)Median follow-up: 34 months. ARR, absolute risk reduction; NA, not applicable.

Disclosure
K.K. Ray: Consultant; Self; Amgen Inc., Sanofi. Research Support; Self; Sanofi. Consultant; Self; The Medicines Company. Research Support; Self; Amgen Inc., Regeneron Pharmaceuticals, Inc.. Consultant; Self; Regeneron Pharmaceuticals, Inc., Pfizer Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk Inc., AstraZeneca, Esperion Therapeutics, Kowa Pharmaceuticals America, Inc.. Research Support; Self; Pfizer Inc.. Consultant; Self; Merck Sharp & Dohme Corp.. Research Support; Self; Merck Sharp & Dohme Corp. H. Colhoun: Research Support; Self; AstraZeneca, Boehringer Ingelheim GmbH. Stock/Shareholder; Self; Bayer AG. Research Support; Self; Eli Lilly and Company. Speaker's Bureau; Self; Eli Lilly and Company. Advisory Panel; Self; Eli Lilly and Company. Other Relationship; Self; Eli Lilly and Company. Advisory Panel; Self; Novartis Pharmaceuticals Corporation. Research Support; Self; Regeneron Pharmaceuticals, Inc.. Advisory Panel; Self; Regeneron Pharmaceuticals, Inc.. Speaker's Bureau; Self; Regeneron Pharmaceuticals, Inc.. Other Relationship; Self; Regeneron Pharmaceuticals, Inc.. Research Support; Self; Pfizer Inc., Roche Pharma. Stock/Shareholder; Self; Roche Pharma. Research Support; Self; Sanofi-Aventis. Advisory Panel; Self; Sanofi-Aventis. Speaker's Bureau; Self; Sanofi. Other Relationship; Self; Sanofi. Research Support; Self; Novo Nordisk Inc. M. Szarek: Consultant; Self; Sanofi, Regeneron Pharmaceuticals, Inc., Baxter, Resverlogix Corp. M. Baccara-Dinet: Employee; Self; Sanofi. D.L. Bhatt: Research Support; Self; Amarin Corporation, Amgen Inc., AstraZeneca, Bristol-Myers Squibb Company, Chiesi USA, Inc., Eisai Inc., Ethicon US, LLC., Forest Laboratories, Inc., Ironwood Pharmaceuticals, Inc., Ischemix, Eli Lilly and Company, Medtronic, Pfizer Inc., Roche Pharma, Sanofi-Aventis, The Medicines Company. Other Relationship; Self; American Heart Association. V. Bittner: Research Support; Self; AstraZeneca, Sanofi, Bayer AG, Esperion Therapeutics, Amgen Inc.. Advisory Panel; Self; Sanofi. Research Support; Self; Dalcor. A.J. Budaj: Other Relationship; Self; Sanofi-Aventis, AstraZeneca, Pfizer Inc., GlaxoSmithKline plc.. Consultant; Self; Bayer AG. Other Relationship; Self; Novartis Pharma K.K., Eisai Co., Ltd.. R. Diaz: None. S.G. Goodman: Research Support; Self; Amgen Inc.. Consultant; Self; Amgen Inc.. Research Support; Self; AstraZeneca. Consultant; Self; AstraZeneca. Research Support; Self; Bayer AG. Consultant; Self; Bayer AG. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc.. Research Support; Self; Bristol-Myers Squibb Company. Consultant; Self; Bristol-Myers Squibb Company. Research Support; Self; Eli Lilly and Company. Consultant; Self; Eli Lilly and Company. Research Support; Self; GlaxoSmithKline plc.. Consultant; Self; Merck & Co., Inc., Novartis Pharmaceuticals Corporation. Research Support; Self; Pfizer Inc.. Consultant; Self; Pfizer Inc.. Research Support; Self; Sanofi. Consultant; Self; Sanofi. Research Support; Self; Regeneron Pharmaceuticals, Inc.. Consultant; Self; Regeneron Pharmaceuticals, Inc.. Research Support; Self; CSL Behring. C.G. Hanotin: Employee; Self; Sanofi. J. Jukema: Research Support; Self; Sanofi-Aventis, Regeneron Pharmaceuticals, Inc., Amgen Inc. V. Loizeau: Employee; Self; Sanofi. R.D. Lopes: Consultant; Self; Bayer AG, Boehringer Ingelheim GmbH. Other Relationship; Self; Bristol-Myers Squibb Company. Consultant; Self; Daiichi Sankyo Company, Limited. Other Relationship; Self; GlaxoSmithKline plc., Medtronic. Consultant; Self; Merck & Co., Inc.. Other Relationship; Self; Pfizer Inc. A. Moryusef: Employee; Self; Sanofi. R. Pordy: Employee; Self; Regeneron Pharmaceuticals, Inc.. A.D. Ristic: None. M. Roe: None. J. Tuñón: Speaker's Bureau; Self; Sanofi-Aventis. Advisory Panel; Self; Sanofi-Aventis. Other Relationship; Self; Sanofi-Aventis. Speaker's Bureau; Self; Amgen Inc. H.D. White: Other Relationship; Self; AstraZeneca, Eli Lilly and Company. Research Support; Self; National Institute for Health and Clinical Excellence. Other Relationship; Self; Omthera Pharmaceuticals, Inc., Pfizer Inc., Eisai Inc.. Research Support; Self; DalCor Pharma UK Inc. Advisory Panel; Self; Sirtex, Actelion Pharmaceuticals US, Inc.. Other Relationship; Self; Luitpold Pharmaceuticals Ltd., CSL Behring, Sanofi-Aventis. G.G. Schwartz: Research Support; Self; Roche Pharma, Sanofi, Resverlogix Corp. P.G. Steg: Consultant; Self; Amarin Corporation, AstraZeneca. Research Support; Self; Bayer AG. Consultant; Self; Bayer AG, Boehringer Ingelheim GmbH, Bristol-Myers Squibb Company. Advisory Panel; Self; Novartis AG. Consultant; Self; Pfizer Inc., Sanofi. Research Support; Self; Sanofi, Servier. Consultant; Self; Novo Nordisk A/S, Regeneron Pharmaceuticals, Inc..