DARWIN EU® - Incidence of myoclonus in heart failure: a descriptive analysis in patients treated with sacubitril/valsartan and other treatments

Study type

• Study topic:
  Human medicinal product
• 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

• Medicinal product name:
  ENTRESTO
• 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:
  Myoclonus

Population studied

• Short description of the study population:
  The source population will include all patients present in the database from January 1st, 2015 (first EU approval of sacubitril/valsartan) to 31st December 2023 (or the last available date). All patients will be required to have at least 365 days of observation time before the index date and be 18 years of age or above at index date.

Study design details

• Study design:
  The incidence of the event of interest will be assessed using a population-level descriptive epidemiology design.
• Main study objective:
  1. To calculate the incidence rate of myoclonus in a newly diagnosed heart failure population and the general population, stratified by age groups and sex. ; 2. To calculate the incidence rate of myoclonus in a heart failure population following first initiation of treatment cohorts: sacubitril/valsartan, angiotensin-converting enzyme inhibitors (ACEi), and angiotensin receptor blockers (ARBs) (index date being the start of the treatment).
• Setting:
  This study used routinely collected health data from 3 databases in the DARWIN EU® network of data partners from 3 European countries.
• Outcomes:
  Incident myoclonus in line with the PRAC signal
• Summary results:
  In this disease epidemiology study of myoclonus in patients with incident HF, HF newly initiating treatments of interest (ACEi, ARBs, and sacubitril/valsartan first and later lines), and the general population in UK, Germany, and Spain, we found that patients with incident HF consistently exhibited higher incidence rates of myoclonus broad and narrow outcomes, when compared to both the HF newly-initiating treatments of interest and general populations. For myoclonus broad, the highest rates for the incident HF and treatment initiator cohorts occurred within the 0-30 days following the start of follow-up. Among new initiators of different treatments of interest in the HF population, when estimable, rates for myoclonus broad were highest among ARBs initiators, and results do not support higher rates among sacubitril/valsartan (later line) treatment. While no significant increase in myoclonus rates was observed across treatment groups, findings should be interpreted with caution due to low event counts, especially for sacubitril/valsartan first line initiators, where numbers were generally too low to provide precise estimates.