Comparative Effectiveness and Safety of Angiotensin-Converting Enzyme Inhibitors (ACEIs) and Angiotensin Receptor Blockers (ARBs) in Older Adults with Type 2 Diabetes

Study type

• Study topic:
  Disease /health condition

  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Drug utilisation

  Effectiveness study (incl. comparative)

  Safety study (incl. comparative)
• Data collection methods:
  Secondary data collection

Non-interventional study

• Non-interventional study design:
  Cohort

  Other
• Non-interventional study design, other:
  Active-comparator, new-user (ACNU) design

Study drug and medical condition

• Anatomical Therapeutic Chemical (ATC) code:
  (C09AA) ACE inhibitors, plain

  (C09CA) Angiotensin II receptor blockers (ARBs), plain
• Medical condition to be studied:
  Type 2 diabetes mellitus

Population studied

• Short description of the study population:
  1. Medicare FFS enrollees ≥65 years of age with T2D having continuous coverage in fee-for-service Medicare plans A (inpatient services), B (physician and outpatient services) and D (prescription drugs); 2. The base population for the analysis will consist of all beneficiaries with ≥1 prescription dispensing claim for ACEI or ARB between January 01, 2007, and December 30, 2019.; We will exclude the following patients:; 1) To ensure new use of either ACEIs or ARBs, we will exclude all individuals who do not have at least 12 months of continuous enrollment (inpatient, outpatient, and prescription coverage) in the appropriate insurance database prior to the first prescription dispensing claim (12-month baseline period), during which no use of any of the study drug classes compared is detected.
• Age groups:
  Adults (65 to < 75 years)

  Adults (75 to < 85 years)

  Adults (85 years and over)
• Special population of interest:
  Hepatic impaired

  Immunocompromised

  Other

  Renal impaired
• Special population of interest, other:
  Type 2 diabetes mellitus patients
• Estimated number of subjects:
  100000

Study design details

• Main study objective:
  1. To estimate absolute and relative rate and risk of in cardiovascular outcomes and all-cause mortality in Medicare beneficiaries with type 2 diabetes (T2D) initiating ACEIs or ARBs. 2. To identify subgroups of Medicare beneficiaries with T2D that are more likely to benefit from ACEI’s or ARBs to prevent cardiovascular outcomes and all-cause mortality using machine learning-based analysis.
• Outcomes:
  The primary outcomes are (i) Hospitalization of Heart failure (HHF) (ii) composite endpoint of inpatient myocardial infarction (MI), inpatient stroke or all-cause mortality (Major Cardiovascular Events, MACE outcome) (iii) the composite of MACE plus HHF. (iv) All-cause mortality (v) end stage renal disease or dialysis, Secondary outcomes include individual components of the MACE outcome (non-fatal MI, stroke, and HHF), and MACE plus invasive cardiac procedures (stents, revascularization, bypass surgery).
• Data analysis plan:
  We will estimate 2-year risks of outcomes of interest, risk differences (RD) and ratios (RR) for ACEIs vs. ARBs after weighting by IPTW and IPCW. Confidence intervals will be derived from 2.5th and 97.5th percentiles of estimates from 500 bootstrap resamples of the study population (random resampling with replacement). When estimating risks of cardiovascular outcomes in older Medicare patients, censoring those who died prior to having the outcome of interest, as commonly done in survival analyses, could bias the risks. To avoid this, we will use Aalen Johansen (AJ) estimators to estimate risks.