Lipid‐lowering efficacy and safety of alirocumab in patients with or without diabetes: A sub‐analysis of ODYSSEY COMBO II

AIM: This sub‐analysis of the ODYSSEY COMBO II study compared the effects of alirocumab, a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, in high cardiovascular risk patients with or without diabetes mellitus (DM) receiving maximally tolerated statin therapy. METHODS: COMBO II was a 104‐week, double‐blind study (n = 720) enrolling patients with documented atherosclerotic cardiovascular disease (ASCVD) and baseline LDL‐C ≥70 mg/dL (1.8 mmol/L), and patients without documented ASCVD at high cardiovascular risk with LDL‐C ≥100 mg/dL (2.6 mmol/L). Patients receiving maximally tolerated statin therapy were randomized (2:1) to alirocumab 75 mg every 2 weeks (Q2W; 1 mL subcutaneous injection) or oral ezetimibe 10 mg daily. Alirocumab dose was increased to 150 mg Q2W (also 1 mL) at Week 12 if Week 8 LDL‐C was ≥70 mg/dL. RESULTS: History of DM was reported in 31% (n = 148) of patients on alirocumab and 32% (n = 77) of patients on ezetimibe. At Week 24, alirocumab consistently reduced LDL‐C from baseline in patients with (−49.1%) or without DM (−51.2%) to a significantly greater extent than ezetimibe (−18.4% and −21.8%, respectively). Occurrence of treatment‐emergent adverse events was similar between groups. Efficacy results at 104 weeks were similar to those at 24 weeks. CONCLUSIONS: Over a 104‐week double‐blind study period, alirocumab provided consistently greater LDL‐C reductions than ezetimibe, with similar LDL‐C results in patients with or without DM. Safety of alirocumab was similar regardless of baseline DM status.