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

Study identification

• PURI:
  https://redirect.ema.europa.eu/resource/44900
• EU PAS number:
  EUPAS44899
• Study ID:
  44900
• Official title and acronym:
  Comparative Effectiveness and Safety of Angiotensin-Converting Enzyme Inhibitors (ACEIs) and Angiotensin Receptor Blockers (ARBs) in Older Adults with Type 2 Diabetes
• DARWIN EU® study:
  No
• Study countries:
  United States
• Study description:
  Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are widely used blood pressure lowering drugs which work by inhibiting the renin-angiotensin system. There are several head-to-head trials assessing the relative effectiveness of these two drug classes. However, the available evidence is limited by small sample size and real-world evidence is conflicting. Therefore, it is necessary to perform a high-quality real-world study to assess the comparative effectiveness of ACEIs to ARBs. More than one-third of the adults with diabetes are currently aged 65 years or older and both ACEIs and ARBs are recommended as first line therapy in type 2 diabetes with hypertension. Thus, to reduce bias and achieve better baseline comparability in real-world study, we propose to assess the comparative effectiveness of ACEIs to ARBs in older adults with type 2 diabetes. We aim to 1) 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) 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 heterogeneous treatment effect analysis. We will conduct active-comparator, new-user cohort using a 20% random sample of Medicare data including patients with ≥1 prescription dispensing claim for ACEI or ARB between January 01, 2007, and December 30, 2019. We will assess the following outcome: (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 and dialysis.
• Study status:
  Finalised

Research institution and networks

Institutions

University of North Carolina at Chapel Hill

Study timelines

Date when funding contract was signed

Planned: 01/08/2017

Actual: 01/08/2017

Study start date

Planned: 29/12/2021

Actual: 29/12/2021

Date of final study report

Planned: 29/12/2021

Actual: 29/12/2021

Sources of funding

Other

More details on funding

National Institute on Aging at NIH

Study protocol

Initial protocol

ACEI v ARB_RWE protocol_30DEC2021

Regulatory

• Was the study required by a regulatory body?:
  No
• Is the study required by a Risk Management Plan (RMP)?:
  Not applicable