A Post-marketing Database Surveillance to Investigate the Risk of Hepatic Events in Hypercholesterolemic Patients Treated with ATOZET or Ezetimibe Atorvastatin coadministration in Japan (MK-0653C-853)

Study type

• Study topic:
  Disease /health condition

  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Assessment of risk minimisation measure implementation or effectiveness
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

  Other
• Non-interventional study design, other:
  Post-marketing database surveillance (PMS)

Study drug and medical condition

• Anatomical Therapeutic Chemical (ATC) code:
  (C10AA05) atorvastatin

  atorvastatin

  (C10AX09) ezetimibe

  ezetimibe

  (C10BA05) atorvastatin and ezetimibe

  atorvastatin and ezetimibe
• Medical condition to be studied:
  Hypercholesterolaemia

Population studied

• Short description of the study population:
  The surveillance populations will include patients with hypercholesterolemia who are: 1) undergoing treatment with ATOZET, or 2) undergoing treatment with coadministration of ezetimibe and atorvastatin, between 1-APR-2018, and 30-SEP-2020, (selection period) in the MID-NET database.; ; Inclusion criteria; 1) Patients who have a hypercholesterolemia diagnosis (ICD code: E78.5) during the selection period,; AND; 2) Patients who have received ATOZET (ATC code: C10BA05) or coadministration of ezetimibe and atorvastatin (ATC code: C10AX09 and C10AA05) during the selection period.; ; The exclusion criteria are as follows:; • For the ATZ-group; 1) Patients given ezetimibe monotherapy (C10AX09) as a pre-treatment drug, OR; 2) Patients given other lipid modifying agents (C10) as a pre-treatment drug except atorvastatin (C10AA05), OR; 3) Patients who were not given any pre-treatment drug, OR; 4) Patients who had ATOZET treatment before April 2018, OR; 5) Patients who do not have a 6-month lookback period prior to the index date, OR; 6) Patients who have any missing information on critical variables (e.g., gender, age), OR; 7) Patients who have severe liver dysfunction considered as the contraindication for the use of ATOZET will be excluded; • For the EZE-ATV-group; 1) Patients given ezetimibe (C10AX09) as a pre-treatment drug, OR; 2) Patients given other lipid modifying agents (C10) as a pre-treatment drug except atorvastatin (C10AX09), OR; 3) Patients who were not given any pre-treatment drug, OR; 4) Patients who had Ezetimibe/Atorvastatin coadministration treatment before April 2018, OR; 5) Patients who do not have a 6-month lookback period prior to the index date, OR; 6) Patients who have any missing information (e.g., gender, age), OR; 7) Patients who have severe liver dysfunction considered as the contraindication for the use of Ezetimibe or Atorvastatin will be excluded.
• Age groups:
  • Adult and elderly population (≥18 years)

    • Adults (18 to < 65 years)

      • Adults (18 to < 46 years)
      • Adults (46 to < 65 years)
    • Elderly (≥ 65 years)

      • Adults (65 to < 75 years)
      • Adults (75 to < 85 years)
      • Adults (85 years and over)
• Special population of interest:
  Hepatic impaired
• Estimated number of subjects:
  2000

Study design details

• Main study objective:
  To compare the incidence rates of hepatic health outcomes of interest (HOI) between those taking ATOZET and those taking the coadministration of ezetimibe and atorvastatin.
• Outcomes:
  The primary hepatic HOI is the combination of hepatic diagnoses (fulminant hepatitis, hepatitis, jaundice) AND laboratory test values (AST > 3 × ULN or ALT > 3 × ULN). The secondary hepatic HOI is hepatic diagnoses (fulminant hepatitis, hepatitis, jaundice) AND/OR various definitions of abnormal AST or ALT.
• Data analysis plan:
  - Calculation of number of hepatic HOI (based on various definitions) per 1,000 person years for the ATOZET and ezetimibe/atorvastatin coadministration groups - Calculation of incidence rate ratios (IRR) of various hepatic HOI, adjusting for covariates, for the ATOZET and ezetimibe/atorvastatin coadministration groups