Background: Acute ischemic stroke (AIS) is a major health challenge, often resulting in long-term disability and death. This study assesses the impact of renin-angiotensin system (RAS) inhibitors (angiotensin-converting enzyme inhibitors and angiotensin receptor blockers) on AIS patient mortality compared to non-RAS antihypertensive medications. Methods: This retrospective cohort study, conducted at Memorial Hermann–Texas Medical Center in Houston, Texas, from August 31, 2017, to August 31, 2022, examined AIS patient mortality. We used a cohort design, evaluating the effects of RAS inhibitors, either alone or in combination with beta-blockers (BBs), while exploring interactions, including those related to end-stage renal disease (ESRD) and serum creatinine levels. Eligible subjects included AIS patients aged 18 or older with specific AIS subtypes who received in-patient antihypertensive treatment. Missing data were addressed using imputation, followed by Inverse Probability of Treatment Weighting (IPTW) to achieve covariate balance. Our primary outcome was mortality rates. Statistical analyses involved cross-sectional and longitudinal approaches, including generalized linear models, G-computation, and discrete time survival analysis over a 20-day follow-up period. Results: In our study of 3058 AIS patients, those using RAS inhibitors had significantly lower in-hospital mortality (2.2%) compared to non-users (12.1%), resulting in a relative risk (RR) of 0.18 (95% CI 0.12-0.26). Further analysis using G-computation revealed a marked reduction in mortality risk associated with RAS inhibitors (Risk 0.0281 vs. 0.0913, Risk Difference (RD) of 6.31% or 0.0631, 95% CI 0.046-0.079). Subgroup analysis demonstrated notable benefits, with individuals having creatinine levels below and above 1.3 mg/dL exhibiting statistically significant RD (RD -0.0510 vs. -0.0895), and a significant difference in paired comparison (-0.0385 or 3.85%, CI 0.023-0.054). Additionally, longitudinal analysis confirmed a consistent daily reduction of 0.93% in mortality risk associated with the intake of RAS inhibitors. Conclusion: RAS inhibitors are associated with a significant reduction in in-hospital mortality in AIS patients, suggesting potential clinical benefits in improving patient outcomes.

The authors have declared no competing interest.

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This study has been approved by the Committee for the Protection of Human Subjects (the UTHSC-H IRB) under protocol HSC-MH-23-0749.

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