Association of angiotensin converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARB) on coronavirus disease (COVID-19) incidence and complications

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

Study drug and medical condition

• Anatomical Therapeutic Chemical (ATC) code:
  (C09) AGENTS ACTING ON THE RENIN-ANGIOTENSIN SYSTEM

  AGENTS ACTING ON THE RENIN-ANGIOTENSIN SYSTEM
• Medical condition to be studied:
  COVID-19

Population studied

• Short description of the study population:
  Hypothesis 1, the cohort will consist of adult patients aged 18 years and over who receive at least one eligible prescription for an exposure drug between 1st November 2019 and 31st January 2020 (with index date set as the last prescription in this window) and are observable in each database for at least one year prior to the index date. Patients are required to have a history of hypertension at any point prior to or including the index date and to be prescribed antihypertensive treatment recommended for first line or initial pharmacological treatment of hypertension at the index date as either monotherapy in one analysis or in combination with other hypertensive treatments that do overlap with the comparison cohort in a second analysis. Cohort exit will be the earliest of: the occurrence of an outcome event; the end of exposure; death; loss or deregistration from the database; or date of last data collection.; Hypothesis 2,We will identify adult patients aged 18 years or over who have an incident diagnosis of COVID19 occurring after 1st December 2019 and assign the date of diagnosis as the index date. Patients will be required to be registered or observable in each database for at least 180 days prior to index date, have a history of hypertension at any point prior to the index date and be a prevalent user of antihypertensive treatment recommended for first line treatment of hypertension as monotherapy at the index date. The end of follow-up will be the earliest occurrence of either: the outcome event, discharge, date of last data collection, end of follow-up (30 days) or death.
• 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:
  Other
• Special population of interest, other:
  COVID-19 patients
• Estimated number of subjects:
  100000

Study design details

• Main study objective:
  To measure the risk of COVID-19 susceptibility and severity in patients exposure to ACE inhibitors and ARBs compared to patient exposed to other antihypertensive agents.
• Outcomes:
  COVID-19 susceptibility and severity, Major acute cardiovascular events (MACE)
• Data analysis plan:
  We will use a prevalent user cohort design to estimate the relative risk of each outcome associated with monotherapy only and monotherapy or combo-therapy comparisons among patients prescribed ACE inhibitors and ARBs compared to patients with diuretics and calcium channel blockers. We will measure the risk of incident COVID-19 diagnosis and also outcomes following hospitalization with COVID-19. Data driven approaches will be used to identify potential covariates for inclusion in matched or stratified propensity score models identified using regularized logistic regression that allow balancing on a large number of baseline potential confounders. Cox regression analysis will be used to calculate hazard ratios. In addition negative control outcomes will allow for evaluating residual bias in the study design.