Efficacy and safety of adding alirocumab to rosuvastatin versus adding ezetimibe or doubling the rosuvastatin dose in high cardiovascular-risk patients: The ODYSSEY OPTIONS II randomized trial. (January 2016)

• Record Type: Journal Article
• Authors: Farnier, Michel; Jones, Peter; Severance, Randall; Averna, Maurizio; Steinhagen-Thiessen, Elisabeth; Colhoun, Helen M.; Du, Yunling; Hanotin, Corinne; Donahue, Stephen
• Is Part Of: Atherosclerosis. Volume 244(2016)
• Page Start: 138
• Page End: 146
• Publication Date: 2016-01
• Subjects: Alirocumab -- Ezetimibe -- Low-density lipoprotein cholesterol -- Monoclonal antibody -- PCSK9 -- Rosuvastatin; Arteriosclerosis -- Periodicals; Electronic journals; 616.136
• DOI: 10.1016/j.atherosclerosis.2015.11.010
• Languages: English
• ISSNs: 0021-9150

Abstract

Abstract: Objective: To compare lipid-lowering efficacy of adding alirocumab to rosuvastatin versus other treatment strategies (NCT01730053). Methods: Patients receiving baseline rosuvastatin regimens (10 or 20 mg) were randomized to: add-on alirocumab 75 mg every-2-weeks (Q2W) (1-mL subcutaneous injection via pre-filled pen); add-on ezetimibe 10 mg/day; or double-dose rosuvastatin. Patients had cardiovascular disease (CVD) and low-density lipoprotein cholesterol (LDL–C) ≥70 mg/dL (1.8 mmol/L) or CVD risk factors and LDL–C ≥100 mg/dL (2.6 mmol/L). In the alirocumab group, dose was blindly increased at Week 12 to 150 mg Q2W (also 1-mL volume) in patients not achieving their LDL–C target. Primary endpoint was percent change in calculated LDL–C from baseline to 24 weeks (intent-to-treat). Results: 305 patients were randomized. In the baseline rosuvastatin 10 mg group, significantly greater LDL–C reductions were observed with add-on alirocumab (−50.6%) versus ezetimibe (−14.4%; p < 0.0001) and double-dose rosuvastatin (−16.3%; p < 0.0001). In the baseline rosuvastatin 20 mg group, LDL–C reduction with add-on alirocumab was −36.3% compared with −11.0% with ezetimibe and −15.9% with double-dose rosuvastatin ( p = 0.0136 and 0.0453, respectively; pre-specified threshold for significance p < 0.0125). Overall, ∼80% alirocumab patients were maintained on 75 mg Q2W. Of alirocumab-treated patients, 84.9% and 66.7% in the baseline rosuvastatin 10 and 20 mg groups, respectively, achieved risk-based LDL–C targets. Treatment-emergent adverse events occurred in 56.3% of alirocumab patients versus 53.5% ezetimibe and 67.3% double-dose rosuvastatin (pooled data). Conclusions: The addition of alirocumab to rosuvastatin provided incremental LDL–C lowering versus adding ezetimibe or doubling the rosuvastatin dose. Highlights: Many high CV risk patients do not achieve their LDL–C goal on current therapies. Adding alirocumab to rosuvastatin reduced LDL–C more than other therapeutic options. Alirocumab 75 mg and 150 mg Q2W dosing regimens allow a treat-to-target approach.