Efficacy and safety of the proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab among high cardiovascular risk patients on maximally tolerated statin therapy: The ODYSSEY COMBO I study.
BACKGROUND The ODYSSEY COMBO I study (http:/clinicaltrials.gov/show/NCT01644175) evaluated efficacy and safety of alirocumab as add on therapy to stable maximally tolerated daily statin with or without other lipid lowering therapy in high cardiovascular risk patients with suboptimally controlled hypercholesterolemia. METHODS This multicenter, phase 3, randomized (2:1 alirocumab vs placebo) double blind, 52 week trial enrolled 316 patients with established coronary heart disease or coronary heart disease risk equivalents and hypercholesterolemia. Alirocumab (75 mg every 2 weeks [Q2W] or placebo Q2W was self administered subcutaneously via 1 mL prefilled pen. The alirocumab dose was increased to 150 mg Q2W (also 1 mL) at week 12 if week 8 low density lipoprotein cholesterol (LDL C) was =70 mg/dL. The primary efficacy end point was percent change in LDL C from baseline to week 24 (intention to treat analysis) RESULTS At week 24, estimated mean (95% CI) changes in LDL C from baseline were 48.2% 52.0% to 44.4% and 2.3% 7.6% to 3.1% for alirocumab and placebo, respectively, an estimated mean (95% CI) difference of 45.9% 52.5% to 39.3% (P .0001) Low density lipoprotein cholesterol <70 mg/dL was achieved by 75% alirocumab versus 9% placebo patients at week 24. At week 12, 83.2% of evaluable alirocumab treated patients remained on 75 mg Q2W. Treatment emergent adverse events were comparable between groups. CONCLUSIONS Alirocumab treatment achieved a significantly greater reduction in LDL C and allowed a greater proportion of patients to achieve LDL C goals, versus placebo after 24 weeks in high cardiovascular risk patients with suboptimally controlled hypercholesterolemia at baseline despite receiving maximally tolerated statin with or without other lipid lowering therapy. The frequency of treatment emergent adverse events and study medication discontinuations were generally comparable between treatment groups.
American heart journal