Efficacy and safety of alirocumab in high cardiovascular risk patients with inadequately controlled hypercholesterolaemia on maximally tolerated doses of statins: the ODYSSEY COMBO II randomized controlled trial.

Aims To compare the efficacy [low-density lipoprotein cholesterol (LDL-C) lowering] and safety of alirocumab, a fully human monoclonal antibody toproproteinconvertase subtilisin/kexin 9,compared with ezetimibe, as add-on therapy tomaximally tolerated statin therapy in high cardiovascular risk patients with inadequately controlled hypercholesterolaemia. Methods and results COMBOII is a double-blind, double-dummy, active-controlled, parallel-group, 104-week study of alirocumab vs. ezetimibe. Patients (n = 720)with high cardiovascular risk and elevated LDL-Cdespitemaximaldoses of statinswere enrolled (August 2012-May 2013). This pre-specified analysis was conducted after the last patient completed 52 weeks. Patients were randomized to subcutaneous alirocumab 75 mg every 2weeks (plus oral placebo) ororal ezetimibe 10 mgdaily (plus subcutaneous placebo) on a background of statin therapy. At Week 24, mean±SE reductions in LDL-C from baseline were 50.6±1.4% for alirocumab vs. 20.7±1.9% for ezetimibe (difference 29.8±2.3%; P < 0.0001); 77.0% of alirocumab and 45.6% of ezetimibe patients achieved LDL-C ,1.8 mmol/L (P<0.0001). Mean achieved LDL-C at Week 24 was 1.3±0.04 mmol/Lwith alirocumab and 2.1±0.05 mmol/Lwith ezetimibe, andweremaintained toWeek 52. Alirocumab was generally well tolerated, with no evidence of an excess of treatment-emergent adverse events. Conclusion In patients at high cardiovascular risk with inadequately controlled LDL-C, alirocumab achieved significantly greater reductions in LDL-C compared with ezetimibe, with a similar safety profile. [ABSTRACT FROM AUTHOR]