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

BACKGROUND

The comparative cardiovascular effectiveness of different renin-angiotensin system (RAS) inhibitors in patients receiving maintenance hemodialysis remains uncertain, and current guideline recommendations largely assume therapeutic equivalence between angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB).

METHODS

Using the TriNetX multi-institutional database, we identified adults with ESKD who newly initiated ARB or ACEI therapy from 2006 to 2025. An active-comparator new-user design and 1:1 propensity score matching were applied. The primary outcome was 1-year major adverse cardiovascular events (MACE: myocardial infarction [MI], stroke, or all-cause mortality). Secondary outcomes included individual MACE components and hyperkalemia. Hazard ratios (HRs) were estimated using Cox models, and negative-control analyses assessed residual confounding.

RESULTS

After matching, 55,894 patients were included. ARB was associated with a lower risk of MACE compared with ACEI users (30.3% vs. 35.0%; HR 0.85; 95% CI 0.83-0.88). Stroke (HR 0.90; 95% CI 0.86-0.94) and all-cause mortality (HR 0.75; 95% CI 0.71-0.78) were also associated with a lower risk, while MI risk was similar (HR 0.99; 95% CI 0.94-1.03). Hyperkalemia rates were comparable. Subgroup findings consistently favored ARBs across age, sex, diabetes, heart failure, CAD, and PAD strata. Negative-control outcomes showed no significant associations.

CONCLUSION

In this large real-world cohort of patients receiving maintenance hemodialysis, initiation of ARB was associated with lower risks of major adverse cardiovascular events, stroke, and all-cause mortality compared with ACEI. These findings suggest a potential difference in observed cardiovascular outcomes between ARBs and ACEIs in the hemodialysis population; however, causal inference is limited by the observational design.