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June 19, 2026Frontiers in PharmacologyOpen Access

Comparative cardiovascular outcomes of renin–angiotensin system inhibitors in patients receiving maintenance hemodialysis: a large real-world cohort study

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Why the study?

Does initiation of ARB reduce 1-year major adverse cardiovascular events compared with ACEI in adults with ESKD receiving maintenance hemodialysis?

Population

55,894 adults with end-stage kidney disease receiving maintenance hemodialysis, mean age 58.5, 60.2% male…

Comparison

Angiotensin receptor blockers newly initiated vs Angiotensin-converting enzyme inhibitors newly…

Design

Cohort

Follow-up

1 year

Key result

Initiation of angiotensin receptor blockers was associated with a lower risk of 1-year major adverse cardiovascular events compared with ACEIs (30.3% vs. 35.0%; HR 0.85) in patients receiving maintenance hemodialysis.

Authors

JWJheng-Yan WuKLKeng-Wei LeeSHS H. M. Huang

Discussion

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Overview

May support ARB over ACEI initiation in ESKD hemodialysis; leaves open confirmation by randomized trials.

Key Points

  • This study aims to assess the comparative cardiovascular effectiveness of RAS inhibitors in patients undergoing maintenance hemodialysis.
  • Utilized the TriNetX database to identify adults with end-stage kidney disease (ESKD) starting ARB or ACEI therapy from 2006 to 2025.
  • Applied 1:1 propensity score matching to create balanced comparison groups.
  • Estimated hazard ratios (HRs) for major adverse cardiovascular events (MACE) using Cox models.
  • After matching, 55,894 patients were analyzed, revealing ARB use associated with a 30.3% MACE rate vs. 35.0% for ACEI (HR 0.85; 95% CI 0.83–0.88).
  • Stroke risk was lower for ARB (HR 0.90; 95% CI 0.86–0.94) and all-cause mortality also lower (HR 0.75; 95% CI 0.71–0.78).
  • No significant difference in myocardial infarction risk (HR 0.99; 95% CI 0.94–1.03) and comparable hyperkalemia rates found.

Study Design

Type

Cohort (n=55,894)

Multicenter

Yes

Structured PICO

Does initiation of ARB reduce 1-year major adverse cardiovascular events compared with ACEI in adults with ESKD receiving maintenance hemodialysis?

P
Population
55,894 adults with end-stage kidney disease receiving maintenance hemodialysis who newly initiated ARB or ACEI therapy, followed for 1 year.
E
Exposure
Angiotensin receptor blockers (ARB) newly initiated
C
Comparator
Angiotensin-converting enzyme inhibitors (ACEI) newly initiated (1:1 propensity score matched active-comparator)
O
Outcome
1-year major adverse cardiovascular events (MACE: composite of myocardial infarction, stroke, or all-cause mortality)composite

Main Result

Hazard Ratio: 0.85 (95% CI 0.83–0.88)

Absolute Event Rate: 30.3% vs 35%

p-value: p=<0.001

In patients with ESKD on maintenance hemodialysis, initiating ARBs rather than ACEIs is associated with a lower 1-year risk of MACE, driven primarily by reductions in stroke and all-cause mortality.

Limitations

  • Potential for patient misclassification or underrepresentation in the registry-based database
  • Reliance on diagnostic and procedural coding introduces misclassification bias
  • Lack of detailed clinical data such as dialysis adequacy, blood pressure variability, and cause-specific mortality
  • Lack of information on medication dose, treatment adherence, or longitudinal treatment changes
  • Potential for residual confounding and indication bias
  • Potential selection bias from requiring a second prescription to confirm sustained treatment exposure
  • Composite endpoint included all-cause mortality rather than cardiovascular mortality
  • Relatively short follow-up duration of 1 year
  • Registry-based database with potential for patient misclassification or underrepresentation
  • Reliance on diagnostic and procedural coding
  • Lack of detailed clinical data including dialysis adequacy, blood pressure variability, and cause-specific mortality
  • Potential for residual confounding or selection bias due to observational design

Cite This Study

Wu et al. (2026) conducted a cohort in End-stage kidney disease (ESKD) receiving maintenance hemodialysis (n=55,894). Angiotensin receptor blockers (ARB) vs. Angiotensin-converting enzyme inhibitors (ACEI) was evaluated on 1-year major adverse cardiovascular events (MACE: myocardial infarction, stroke, or all-cause mortality) (HR 0.85, 95% CI 0.83-0.88, p=<0.001). Initiation of angiotensin receptor blockers was associated with a lower risk of 1-year major adverse cardiovascular events compared with ACEIs (30.3% vs. 35.0%; HR 0.85) in patients receiving maintenance hemodialysis.

synapsesocial.com/papers/6a35982fdd3be7785e70ec9dhttps://doi.org/10.3389/fphar.2026.1833065
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Also Consider

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  3. 3ACE Inhibitors vs ARBs in Hypertensive Diabetics: A systematic review of cardiovascular mortality and renal outcomes2025
  4. 4A comparative analysis of ACE Inhibitors and ARBs as cancer risk factors2026
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