Reviving Decades-Old Wisdom: Longitudinal Analysis of Renin-Angiotensin System Inhibitors and its effects on Acute Ischemic Stroke to Improve Outcomes

Sophie Samuel; Kyndol Craver; Charles Miller; Brittany Pelsue; Catherine Gonzalez; Teresa A Allison; Brian Gulbis; H Alex Choi; Seokhun Kim

doi:10.1093/ajh/hpae033

Reviving Decades-Old Wisdom: Longitudinal Analysis of Renin-Angiotensin System Inhibitors and its effects on Acute Ischemic Stroke to Improve Outcomes

Am J Hypertens. 2024 Mar 19:hpae033. doi: 10.1093/ajh/hpae033. Online ahead of print.

Authors

Sophie Samuel¹, Kyndol Craver¹, Charles Miller², Brittany Pelsue¹, Catherine Gonzalez³, Teresa A Allison¹, Brian Gulbis¹, H Alex Choi⁴, Seokhun Kim²

Affiliations

¹ Department of Pharmacy, Memorial Hermann Hospital, Houston, Texas, USA.
² Institute of Clinical Research and Learning Health Care, UT Health Houston, Houston, Texas USA.
³ Department of Neurosurgery, UT Health Houston, Texas, USA.
⁴ Department of Neurology, UT Health Houston, Houston, Texas, USA.

PMID: 38501167
DOI: 10.1093/ajh/hpae033

Abstract

Background: While Renin-Angiotensin System (RAS) inhibitors have a longstanding history in blood pressure control, their suitability as first-line in-patient treatment may be limited due to prolonged half-life and kidney failure concerns.

Methods: Using a cohort design, we assessed the impact of RAS inhibitors, either alone or in combination with beta-blockers, on mortality, while exploring interactions, including those related to end-stage renal disease and serum creatinine levels. Eligible subjects were AIS patients aged 18 or older with specific subtypes who received in-patient antihypertensive treatment. The primary outcome was mortality rates. Statistical analyses included cross-sectional and longitudinal approaches, employing 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 (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.

Keywords: Acute Ischemic Stroke; Beta Blockers; ESRD; Longitudinal Analysis; Mortality; RAS Inhibitors; Serum Creatinine.