Non-interventional post-authorization multi-database safety study to assess the risk of myotoxicity, hepatotoxicity and acute pancreatitis in statin-exposed heart failure patients with or without concomitant use of sacubitril/valsartan (Entresto®)

Study type

• Study type:
  Non-interventional study
• Scope of the study:
  Assessment of risk minimisation measure implementation or effectiveness

Non-interventional study

• Non-interventional study design:
  Case-control

Study drug and medical condition

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

  VALSARTAN
• Anatomical Therapeutic Chemical (ATC) code:
  100000166629

  valsartan and sacubitril
• Medical condition to be studied:
  Chronic left ventricular failure

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:
  7117

Study design details

• Main study objective:
  To assess individually the relative risk of myotoxic events, hepatotoxic events, and acute pancreatitis associated with concomitant exposure of LCZ696 together with statins compared with statin exposure alone in adult patients with HF using rea-world data.
• Outcomes:
  Myotoxic events Hepatotoxic events Acute pancreatitis
• Data analysis plan:
  Demographic and clinical characteristics of case and control patients at the index date will be described separately for each outcome of interest using contingency tables for categorical variables and mean, standard deviation (sd), range, median and interquartile range (IQR) for continuous variables in each individual database. Conditional logistic regression analyses will be used to estimate crude and adjusted odds ratios (ORs) of each specific outcome with corresponding 95% confidence intervals (CIs). The primary analysis is current LCZ696 and statin versus current use of statin (any dose) without current use of LCZ696. Secondary analyses comprise investigation of dose of statin and duration of LZC696, recent use of LZC696 or statins, and individual statins. In dose specific analysis for statins the reference category will be current low dose of statins and non-use of LCZ696. Control for confounding will be based on matching (1:4 case: control ratio) and confounder adjustment.