Real-world Comparative Effectiveness of Evolocumab Versus Ezetimibe in Reducing the Risk of Fatal and Nonfatal Myocardial Infarction (20240027)

Study type

• Study topic:
  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Effectiveness study (incl. comparative)

Non-interventional study

• Non-interventional study design:
  Other
• Non-interventional study design, other:
  Observational retrospective cohort study

Study drug and medical condition

• Name of medicine:
  REPATHA
• Study drug International non-proprietary name (INN) or common name:
  EVOLOCUMAB
• Anatomical Therapeutic Chemical (ATC) code:
  (C10AX13) evolocumab

  evolocumab
• Medical condition to be studied:
  Myocardial infarction

Population studied

• Short description of the study population:
  Adult patients with ASCVD who were new users of evolocumab or ezetimibe
• Estimated number of subjects:
  423556

Study design details

• Study design:
  It is an observational retrospective cohort study to compare treatment effectiveness of evolocumab vs. ezetimibe in reducing risk of fatal and nonfatal myocardial infarction in US adult patients with ASCVD.
• Main study objective:
  The primary objectives of this study are to describe weighted and unweighted baseline demographic and clinical characteristics among new users of evolocumab or ezetimibe, utilize a staged approach to assess the sample size, comparability, and potential uncontrolled confounding between the new users of evolocumab or ezetimibe using negative control outcomes (NCOs), and compare the risk of fatal and nonfatal myocardial infarction (MI) between the new users of evolocumab and ezetimibe.
• Setting:
  The study cohort will be drawn from Komodo’s Healthcare Map and will consist of U.S. adults (aged ≥18 years at initiation of evolocumab or ezetimibe) with documented history of ASCVD and statin use, who were new users of evolocumab or ezetimibe (no prior use of PSCK9i, ezetimibe, or bempedoic acid) between 01 January 2017 and 31 December 2023. ; Patients will be followed up to compare effectiveness of treatment with evolocumab vs. ezetimibe in reducing risk of fatal and nonfatal MI.
• Comparators:
  New users of evocolumab vs. new users of ezetimibe
• Outcomes:
  Risk of fatal and nonfatal MI using cumulative risk, risk difference, and risk ratio
• Data analysis plan:
  Primary Objective 1; Descriptive analyses will be conducted to assess weighted and unweighted baseline participant demographic characteristics, clinical history and medication use for evolocumab and ezetimibe cohorts. ; Comparability of the evolocumab and ezetimibe cohorts will be assessed by calculating standardized mean differences of variables included in the propensity-score model, and assessing the distributions and amount of overlap in propensity scores for the two treatment groups.; Primary Objective 2; 2, 3 and 4-year cumulative incidences, risk differences (RD) and risk ratios (RR) and their 95% confidence intervals will be estimated for each NCO comparing the evolocumab cohort with the ezetimibe cohort. Inverse probability of treatment and censoring weights will be used to account for confounding at baseline and potentially informative censoring. ; Deaths will be included as competing events for analyses of individual NCOs. A table will be created of outcome frequencies within each treatment cohort. If NCO analyses indicate acceptable levels of residual bias and there is sufficient sample size to detect clinically meaningful differences in outcomes Primary Objective 3 will go ahead. ; If NCO analyses indicate that confounding is not adequately controlled the inclusion/exclusion criteria and propensity score models will be re-evaluated to address remaining bias until an acceptable threshold is met.; Primary Objective 3; Plots will be created of the 2, 3 or 4-year cumulative incidences of fatal and nonfatal MI outcomes in the population overall and within each treatment cohort. ; RDs and RRs and their 95% confidence intervals for fatal and nonfatal MI will be estimated comparing the evolocumab cohort with the ezetimibe cohort. ; Inverse probability of treatment and censoring weights will be utilized to account for confounding at baseline and potentially informative censoring. Deaths attributed to causes other than MI will be included as competing events.;
• Summary results:
  Not available