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

Diabetes Obes Metab. 2017 Jul;19(7):989-996. doi: 10.1111/dom.12909. Epub 2017 Apr 18.

Abstract

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.

Keywords: cardiovascular disease; clinical trial; dyslipidaemia; type 1 diabetes; type 2 diabetes.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • Cardiovascular Diseases / complications
  • Cardiovascular Diseases / epidemiology
  • Cardiovascular Diseases / prevention & control*
  • Cholesterol, LDL / blood
  • Cohort Studies
  • Combined Modality Therapy / adverse effects
  • Diabetes Complications / blood
  • Diabetes Complications / drug therapy*
  • Diabetes Complications / prevention & control
  • Diabetes Complications / therapy
  • Double-Blind Method
  • Drug Administration Schedule
  • Drug Therapy, Combination / adverse effects
  • Female
  • Follow-Up Studies
  • Healthy Lifestyle
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Hyperlipidemias / blood
  • Hyperlipidemias / complications
  • Hyperlipidemias / drug therapy*
  • Hyperlipidemias / therapy
  • Hypolipidemic Agents / administration & dosage
  • Hypolipidemic Agents / adverse effects
  • Hypolipidemic Agents / therapeutic use*
  • Injections, Subcutaneous
  • Male
  • Middle Aged
  • Proprotein Convertase 9 / antagonists & inhibitors*
  • Risk Factors
  • Serine Proteinase Inhibitors / administration & dosage
  • Serine Proteinase Inhibitors / adverse effects
  • Serine Proteinase Inhibitors / therapeutic use*

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Cholesterol, LDL
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Hypolipidemic Agents
  • Serine Proteinase Inhibitors
  • Proprotein Convertase 9
  • alirocumab