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

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.

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.