P1512Assessment of absolute reductions in LDL-C associated with alirocumab therapy: results from across the Phase 3 ODYSSEY programme

Abstract

Background: Until now, assessment of efficacy of alirocumab (ALI), a PCSK9 inhibitor, has focused on percent change in LDL-C from baseline. However, by extension of the Cholesterol Treatment Trialists' (CTT) meta-analysis model (every 1 mmol/L reduction in LDL-C corresponds to a 22% reduction in major vascular events), assessment of ALI by absolute change in LDL-C may allow characterisation of potential impact on cardiovascular risk. Purpose: To determine absolute reductions from baseline in LDL-C with ALI, stratified by baseline LDL-C. used 75 mg every 2 weeks [Q2W], with potential dose increase to 150 mg Q2W at Week (W)12 if pre-specified LDL-C goals not achieved at W8 [ALI 75up150 mg]; two trials used 150 mg Q2W only) and stratified by baseline LDL-C. Results: At W24, 28% (378 of 1363 patients) had dose increase from ALI 75 to 150 mg. Absolute reductions in LDL-C associated with ALI were directly proportional to baseline values (Table). For patients with the highest baseline LDL-C values (≥190 mg/dL; ≥4.9 mmol/L), absolute LDL-C reductions at W24 translate to predicted cardiovascular risk reductions (using the CTT model) of 72% (maintained 75 mg), 71% (75up150 mg) and 74% (150 mg throughout). ALI safety profile was similar to comparator (placebo or ezetimibe), except for a higher incidence of injection-site reactions with ALI. Conclusions: Substantial absolute reductions in LDL-C, proportional in size to baseline LDL-C, were observed with both ALI doses.