Effectiveness of PCSK9 Inhibitors in Familial Hypercholesterolemia: Feasibility Analysis

Study type

• Study topic:
  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Drug utilisation

  Feasibility analysis
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Name of medicine:
  PRALUENT

  REPATHA
• Study drug International non-proprietary name (INN) or common name:
  ALIROCUMAB

  EVOLOCUMAB
• Anatomical Therapeutic Chemical (ATC) code:
  (C10AX13) evolocumab

  evolocumab

  (C10AX14) alirocumab

  alirocumab
• Additional medical condition(s):
  Heterozygous Familial Hypercholesterolemia

Population studied

• Short description of the study population:
  The study population will include all patients aged 10 years or older (66 years or older in Ontario) who began treatment with a PCSK9i in the study provinces between April 1, 2015 (or the date of the first claim for PCSK9i in each province) and March 31, 2023.
• Age groups:
  Children (2 to < 12 years)

  Adolescents (12 to < 18 years)

  Adult and elderly population (≥18 years)
• Estimated number of subjects:
  20000

Study design details

• Study design:
  Descriptive cohort study
• Main study objective:
  The main objectives are:; 1. To determine the percentage of patients with FH who are achieving the public drug plans’ recommended treatment goal of at least 40% reduction in LDL-C during treatment with PCSK9i.; 2. To estimate the incidence of major adverse cardiovascular events among patients with FH who are prescribed PCSK9i.
• Setting:
  Using administrative healthcare data from the provinces of Alberta, British Columbia, and Ontario, we will identify patients who began treatment with a PCSK9i (alirocumab or evolocumab) between 2015 and 2023. PCSK9i initiators will be identified using prescription drug claims, and FH status will be inferred using a combination of public drug plan reimbursement (which is limited to those with FH) and laboratory test values for LDL-C (using an adaptation of Ruel et al.’s criteria). To ensure patients are new users, we will require a minimum of 365 days of data availability with no prescription for PCSK9i. Cohort entry will be defined as the date of the first dispensing of a PCSK9i. For the purposes of cardiovascular outcome assessment, patients will be followed from the date of cohort entry to the first of: a major adverse cardiovascular event, treatment discontinuation, loss of health insurance, death, or end of the study period.
• Outcomes:
  We will study 4 sets of measures:; ; 1. Patient characteristics at cohort entry (sociodemographic and clinical characteristics); ; 2. Duration of PCSK9i therapy; ; 3. Attainment of LDL-C treatment targets: Among patients for whom the required laboratory data are available, we will determine the percentage who:; a. Achieve the public drug plan’s recommended 40% reduction in LDL-C within 8 weeks of PCSK9i initiation; b. Maintain the public drug plan’s recommended 40% reduction in LDL-C during PCSK9i therapy; c. Achieve the 2021 Canadian Cardiovascular Society post-treatment absolute LDL-C thresholds for primary prevention (no previous atherosclerotic cardiovascular disease (ASCVD)) or secondary prevention (previous ASCVD) within 8 of PCSK9i initiation; d. Achieve specific LDL-C thresholds within 8 weeks of PCSK9i initiation for primary and secondary prevention patients; ; 4. Incidence of major adverse cardiovascular events (MACE): defined a composite outcome previously used in a CNODES study (Filion et al. 2020), consisting of myocardial infarction, ischemic stroke, or cardiovascular death (using the algorithm previously validated by Lix et al. 2021); ; The incidence of MACE during treatment will be estimated to support assessment of the feasibility of future observational studies of PCSK9i.
• Data analysis plan:
  Analyses will be completed in each provincial database with measures pooled cross-provincially as appropriate. First, patient characteristics at the time of PCSK9i initiation will be described. Second, the mean and median duration of PCSK9i therapy will be estimated, from the date of treatment initiation to the date of discontinuation. Third, the percentage of patients achieving the LDL-C treatment targets (described above) will be determined. Fourth, the crude and age- and sex-standardized incidence rate and corresponding 95% confidence intervals of MACE will be estimated among all PCSK9i initiators and among the subset with and without a history of these events, and those with and without a history of ASCVD. MACE will also be computed by subgroups. Last, a sensitivity analysis will be conducted for the attainment of LDL-C targets in the subset of patients with baseline measures in a shorter timeframe preceding PCSK9i initiation.

Documents

Study, other information

Link to project page on CNODES website.

Major adverse cardiovascular events definition

Cardiovascular death algorithm definition