Efficacy and safety of alirocumab vs ezetimibe in statin-intolerant patients, with a statin rechallenge arm: The ODYSSEY ALTERNATIVE randomized trial

Abstract

Alirocumab produced greater LDL-C reductions than ezetimibe in statin-intolerant patients, with fewer skeletal-muscle adverse events vs atorvastatin.

Efficacy and safety of alirocumab among individuals with diabetes mellitus and atherosclerotic cardiovascular disease in the ODYSSEY phase 3 trials

“…The percentage reduction in Lp(a) observed in individuals with DM and ASCVD who were treated with alirocumab was similar to that observed in the overall alirocumab‐treated patient populations in the ODYSSEY trials,39 with the exception of the pool without statins. For the DM and ASCVD population, Lp(a) changes from baseline were −36.0% with alirocumab and +10.0% with ezetimibe, compared with −25.9% with alirocumab and −7.3% with ezetimibe in the overall population 25. These differences are possibly a result of the small number of individuals with DM and ASCVD in that pool.…”

“…There were relatively few individuals in the pool with no background statin therapy (ie, the ALTERNATIVE study), which probably contributes to some discrepancies that were observed in this pool, including imbalances in baseline LDL‐C between alirocumab and ezetimibe groups, and an observed 4% increase in LDL‐C from baseline in the ezetimibe group; in the primary trial, ALTERNATIVE, LDL‐C reductions from baseline to Week 24 were 45.0% with alirocumab and 14.6% with ezetimibe 25. The analysis of glycaemic parameters is limited by the duration of the trials, the longest follow‐up being 104 weeks.…”

“…This post‐hoc pooled analysis included individuals with a medical history of Type 1 or Type 2 DM and ASCVD who participated in 9 randomized, double‐blind, placebo‐ or ezetimibe‐controlled ODYSSEY Phase 3 trials with subcutaneous alirocumab administered every 2 weeks (Q2W), with trial durations of 24‐104 weeks (LONG TERM [NCT01507831],26 FH I [NCT01623115],23 FH II [NCT01709500],23 HIGH FH [NCT01617655],22 COMBO I [NCT01644175],24 COMBO II [NCT01644188],20 OPTIONS I [NCT01730040],19 OPTIONS II [NCT01730053]21 and ALTERNATIVE [NCT01709513]) 25. Individual trial results have been published previously.…”

“…Alirocumab is a PCSK9 inhibitor that signficantly reduced LDL‐C and other atherogenic lipid parameters in participants with hypercholesterolaemia in Phase 3 ODYSSEY trials,19, 20, 21, 22, 23, 24, 25, 26 including dedicated trials involving individuals with DM who were receiving insulin therapy27 or with mixed dyslipidaemia,28 with a safety profile comparable to controls. Alirocumab has also been demonstrated to reduce major adverse cardiovascular events vs placebo in patients with recent acute coronary syndrome in the ODYSSEY OUTCOMES trial 29.…”

PCSK9 Inhibitors in Lipid Management of Patients With Diabetes Mellitus and High Cardiovascular Risk: A Review

“…Alirocumab and evolocumab, either alone or in combination with statins and/or other lipid‐lowering therapies, have been shown in their respective phase 3 clinical trial programs (ODYSSEY and PROFICIO [Program to Reduce LDL‐C and Cardiovascular Outcomes Following Inhibition of PCSK9 In Different Populations]) to significantly reduce LDL‐C levels by up to 60% from baseline (depending on dosing regimen; Table) in patients with hypercholesterolemia, including those with familial hypercholesterolemia, moderate to very high cardiovascular risk, and statin intolerance 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62. The inclusion/exclusion criteria and other details of each phase 3 ODYSSEY and PROFICIO trial are shown in Table S2.…”