Non-interventional post-authorization multi-database safety study to characterize the risk of angioedema and other specific safety events of interest in association with use of Entresto® (sacubitril/valsartan) in adult patients with heart failure

Study type

• Study type:
  Non-interventional study
• Scope of the study:
  Safety study (incl. comparative)
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

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

  VALSARTAN
• Anatomical Therapeutic Chemical (ATC) code:
  (C09DX04) valsartan and sacubitril

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

  Cardiac failure

Population studied

• Short description of the study population:
  Adult patients with heart failure
• 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:
  24000

Study design details

• Study design:
  A non-interventional, cohort study using European healthcare database information in a population of adult patients with prevalent or incident HF, newly starting treatment with sacubitril/valsartan (with or without prior exposure to ACEIs or ARBs), or ACEIs (as new users, and prevalent users).
• Main study objective:
  The primary objectives of the study were:; - To estimate the incidence of specific safety events of interest in adult patients with HF newly starting treatment with sacubitril/valsartan (regardless of prior exposure to ACEIs or angiotensin receptor blockers [ARBs]).; - To estimate the incidence of all safety events of interest in adult HF patients newly starting treatment with sacubitril/valsartan without prior exposure to ACEIs or ARBs.
• Outcomes:
  Angioedema is the primary safety event of interest, hypotension, hyperkalemia, hepatotoxicity, and renal impairment are secondary safety events of interest.
• Data analysis plan:
  Demographic and baseline characteristics of patients initiating sacubitril/valsartan or ACEIs will be described using contingency tables for categorical variables and mean, SD, range, median and IQR for continuous variables in each database. The risk of the outcomes of interest will be assessed as incidence rates (IRs) along with 95% confidence intervals (CIs) in users of sacubitril/valsartan and ACEIs. Exploratory: Adjusted relative risks of angioedema will be estimated as hazard ratios (HRs) with 95% CIs among new users of sacubitril/valsartan, (a) who are treatment-naïve to ACEIs and ARBs, and (b) separately, in LCZ696 initiators regardless of prior ACEI or ARB use, relative to new users of ACEIs (treatment-naïve to ACEIs) by using Cox regression models.