Safety and efficacy of alirocumab in patients with hypercholesterolemia and high cardiovascular risk in a real-life setting

MAIN TAKEAWAY

In high-risk patients with severe hypercholesterolemia receiving maximum tolerated dose (MTD) of statins ± lipid-lowering therapies (LLTs):

Add-on therapy with alirocumab was shown to be generally well tolerated, with the incidence of treatment-emergent adverse events (TEAEs) being similar to those reported in previous trials

Treatment with alirocumab reduced low-density lipoprotein cholesterol (LDL-C) levels by over 50% from baseline to Week 12; this was sustained throughout the treatment duration (up to 2 years)

WHY THIS MATTERS

Familial hypercholesterolemia (FH) is associated with increased cardiovascular (CV) risk

In clinical practice, despite MTD therapy (with or without ezetimibe), many patients with heterozygous FH (HeFH) fail to attain guideline-recommended LDL-C goals without additional LLTs. Statin intolerance remains a concern in some patients, and discontinuation of statin therapy may cause an increase in CV events

STUDY DESIGN

  • ODYSSEY APPRISE (NCT02476006), a real-life European/Canadian, prospective, single-arm, phase 3b, open-label study, duration ≥12 weeks to ≤30 months, evaluated the safety and efficacy of alirocumab (subcutaneous dosing regimen: 75 or 150 mg every 2 weeks, dose adjustment allowed at investigator’s discretion)
    • Alirocumab was administered on top of background MTD statin (rosuvastatin 20 or 40 mg/day, atorvastatin 40 or 80 mg/day, or simvastatin 80 mg/day) ± other LLTs
  • Eligibility criteria: Patients aged ≥18 years, with HeFH or with non-familial hypercholesterolemia and established coronary heart disease (CHD) or a CHD risk equivalent, and with hypercholesterolemia not adequately controlled with MTD ± LLT
  • Primary endpoint: To assess safety parameters including treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (TESAEs)
  • Main secondary (efficacy) endpoint: The percent change in calculated LDL-C from baseline to Week 12

KEY RESULTS

SAFETY

  • Overall, 994 patients were enrolled and treated, with a mean duration of alirocumab exposure [SD] = 72.4 [42.5] weeks
  • Primary endpoint: TEAEs were reported in 712/994 patients
    • Four deaths were reported during the on-study period: 2 were during the TEAE period but were not considered as related to alirocumab. Three additional deaths occurred post-study
    • 45/994 patients permanently discontinued treatment due to a TEAE
    • 161/994 patients developed TESAEs; 9/994 patients were considered to have TESAEs related to alirocumab
    • 34/994 patients had TEAEs corresponding to AEs of special interest

EFFICACY

  • Secondary endpoint: Mean (SD) LDL-C level decreased by 2.6 (1.2) mmol/L from baseline to Week 12 (54.8%; modified intention-to-treat population). This reduction was maintained throughout the study duration

LIMITATIONS

  • The study lacked a comparative control and a treatment bias may exist owing to the open-label design
  • Limited applicability of the study findings to other patient populations
  • Data on new-onset diabetes and changes in lipoprotein(a) levels were missing

    Gaudet D, López-Sendón JL, Averna M, Bigot G, Banach M, Letierce A, et al. Safety and efficacy of alirocumab in a real-life setting: the ODYSSEY APPRISE study. Eur J Prev Cardiol. 2020:zwaa097. doi: 10.1093/eurjpc/zwaa097. Epub ahead of print. PMID: 33624041.

MAT-BH-2100648/v1/Jul 2021