Abstract 16194: PCSK9 Inhibitor Alirocumab as Add-on to Atorvastatin versus Other Lipid Treatment Strategies in Patients at High CVD Risk: ODYSSEY OPTIONS I
Introduction: Not all patients at high cardiovascular (CV) risk achieve sufficient reduction in LDL-C levels by commonly used statin doses. Among patients treated with atorvastatin (ATV) 20 or 40 mg who did not achieve specified LDL-C treatment levels, ODYSSEY OPTIONS I compared: (1) adding the PCSK9 antibody, alirocumab; (2) adding ezetimibe (EZE); (3) doubling ATV dose, or (4) switching to rosuvastatin 40 mg.
Methods: A Phase 3, randomized, double-blind, active-comparator and parallel-group study (NCT01730040) in high CV risk patients with CVD and LDL-C ≥70 mg/dL or without CVD but with CVD risk factors and LDL-C ≥100 mg/dL. Patients had stable ATV 20 or 40 mg/day for ≥4 weeks prior to study entry. Within each baseline ATV dose regimen, randomization included (Figure): (1) add-on alirocumab 75 mg administered subcutaneously (SC) every 2 weeks (Q2W) using a 1-mL autoinjector; (2) add-on EZE orally (PO) 10 mg/day; (3) doubling of ATV dose; or (4) switch from ATV 40 mg to rosuvastatin 40 mg (for ATV cohort 40 mg). Alirocumab dose was up-titrated at Week 12 in a blinded manner to 150 mg Q2W (using a 1-mL autoinjector) in patients not achieving their predetermined LDL-C level. The primary endpoint was the % change in calculated LDL-C from baseline to 24 weeks in the intent-to-treat population, and with prespecified on-treatment analysis.
Results: In total, 355 patients were randomized: 231 (65.1%) were male, mean (SD) age was 62.9 (10.2) years, 211 (59.4%) had CHD, 178 (50.1%) had diabetes, and mean (SD) baseline LDL-C was 105.1 (34.1) mg/dL. Primary efficacy and safety analyses will be available for AHA.
Conclusions: OPTIONS I is the only clinical trial of a PCSK9 inhibitor to compare alirocumab as add-on therapy to ATV to commonly used lipid treatment strategies: (1) addition of EZE, (2) doubling statin dose, or (3) a switch to more potent statin, in high CV-risk patients.
Author Disclosures: H. Bays: Research Grant; Significant; Alere, Amarin, Amgen, Ardea, Astra Zeneca, Boehringer Ingelheim, Bristol-Myers Squibb, California Raisin Board, Catabasis, Cymabay, Eisai, Elcelyx, Eli Lilly, Esperion, Forest, Gilead, Given, GlaxoSmithKline, Hanmi, Hisun, High Point Pharmaceuticals LLC, F. Hoffman LaRoche, Home Access, Janssen, Merck, Metabolex, Necktar, Novartis, Novo Nordisk, Omthera, Orexigen, Pfizer, Pronova, Regeneron, Sanofi, Takeda, TIMI, Transtech Pharma, Trygg, VIVUS, Wpu Pharmaceuticals. Speakers Bureau; Modest; Amarin, Eisai, Merck. Honoraria; Modest; Amgen, Bristol Meyers Squibb, Catabasis, Daiichi Sankyo, Eisai, Isis, Merck, Novartis, Omthera, VIVUS, WPU. Honoraria; Significant; Amarin, Astra-Zeneca. Consultant/Advisory Board; Modest; Amgen, Bristol Meyers Squibb, Catabasis, Daiichi Sankyo, Eisai, Isis, Merck, Novartis, Omthera, VIVUS, WPU. Consultant/Advisory Board; Significant; Amarin, Astra-Zeneca. D. Gaudet: Consultant/Advisory Board; Modest; Sanofi, Regeneron, Novartis, Isis, Catabasis, Aegerion, Amgen. R. Weiss: Research Grant; Modest; Sanofi, Amgen, Pfizer. J. Lima Ruiz: None. G.F. Watts: Research Grant; Significant; Amgen, Sanofi. Speakers Bureau; Modest; Merck. Consultant/Advisory Board; Modest; Amgen, Sanofi. I. Gouni-Berthold: Speakers Bureau; Modest; Sanofi, Amgen. Honoraria; Modest; Sanofi, Amgen. Consultant/Advisory Board; Modest; Amgen. J.G. Robinson: Research Grant; Significant; Amarin, Amgen, Astra-Zeneca, Daiichi-Sankyo, Genentech/Hoffman La Roche, Glaxo-Smith Kline, Merck, Regeneron/Sanofi, Zinfandel/Takeda.. Consultant/Advisory Board; Significant; Amgen, Hoffman LaRoche, Merck, Pfizer, Sanofi. J. Zhao: Employment; Significant; Regeneron (Contractor). C. Hanotin: Employment; Significant; Sanofi. S. Donahue: Employment; Significant; Regeneron Pharmaceuticals, Inc.
- © 2014 by American Heart Association, Inc.