A Post-marketing Database Surveillance to Investigate the Risk of Rhabdomyolysis and Myopathy in Hypercholesterolemic Patients Treated with ATOZET or Ezetimibe Atorvastatin coadministration in Japan (MK-0653C-854)

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

  Safety study (incl. comparative)
• 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

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, OR; (8) Patients whose CK level exceeded the ULN in the 6 months before index date, OR; (9) Patients who were diagnosed with rhabdomyolysis or myopathy in the 6 months before the index date 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 (C10AA05), 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 a
• 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)
• Special population of interest:
  Hepatic impaired
• Estimated number of subjects:
  2000

Study design details

• Main study objective:
  To compare the incidence rates of muscle HOI between those taking ATOZET and those taking the coadministration of ezetimibe and atorvastatin.
• Outcomes:
  The primary HOIs are the combination of a rhabdomyolysis diagnosis code AND laboratory test value (CK >10 x upper limit of normal) and the combination of a myopathy diagnosis code AND laboratory test value (CK > 10 x upper limit of normal). The secondary HOIs are a rhabdomyolysis or myopathy diagnosis code AND/OR various definitions of an abnormal CK laboratory test value.
• Data analysis plan:
  - Calculation of number of muscle 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 muscle HOI, adjusting for covariates, for the ATOZET and ezetimibe/atorvastatin coadministration groups

Documents

Study results

MK-0653C-854-CSR_final redaction