The Cardiovascular Multi-dimensional Observational Investigation of the Use of PCSK9 Inhibitors (20180059) (cvMOBIUS)

Study type

• Study type:
  Non-interventional study
• Scope of the study:
  Drug utilisation

  Effectiveness study (incl. comparative)

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

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

  evolocumab

  (C10AX14) alirocumab

  alirocumab
• Medical condition to be studied:
  Myocardial infarction

  Coronary artery disease

  Peripheral arterial occlusive disease

  Hyperlipidaemia

  Ischaemic stroke

Population studied

• Age groups:
  Adults (18 to < 46 years)

  Adults (46 to < 65 years)

  Adults (65 to < 75 years)

  Adults (75 to < 85 years)

  Adults (85 years and over)
• Estimated number of subjects:
  8500

Study design details

• Main study objective:
  To evaluate the real-world effectiveness of PCKS9 inhibitors to reduce cardiovascular events in routine practice in a prospective cohort of adults presenting with a recent atherosclerotic cardiovascular disease (ASCVD) event and/or revascularization procedure.
• Outcomes:
  Time to event from baseline for the first of all-cause mortality, any non-fatal myocardial infarction, any non-fatal ischemic stroke, The individual components of the primary endpoint, coronary, peripheral or carotid revascularization procedures, major adverse limb events (MALE) including amputation, cardiovascular death, transient ischemic attack (TIA), unstable angina (UA)
• Data analysis plan:
  The primary analysis will use a marginal structural model (MSM) approach to evaluate the relative risk of the primary composite outcome (all-cause mortality, non-fatal MI, and non-fatal IS) in PCSK9i users versus non-users, while accounting for the time varying nature of PCSK9i initiation and discontinuation, and factors related to initiation and discontinuation as they change over time. Following the database lock and prior to the primary effectiveness analysis, we will implement a descriptive analysis to evaluate whether baseline characteristics are balanced between users and non-users of PCSK9is. The primary analysis will parallel an on-treatment analysis, where subjects who discontinue PCSK9i will be censored after six months off therapy. Hazard ratios will be output from a Cox proportional hazards model, weighted by inverse probability to treat weights (IPTW) and inverse probability of censoring weights (IPCW). The same approach will be used for the secondary outcomes