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 Jun 14;37(7):531-539. 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 Acute Ischemic Stroke (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 3,058 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.

Conclusions: 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; ESRD; RAS inhibitors; beta-blockers; blood pressure; hypertension; longitudinal analysis; mortality; serum creatinine.

MeSH terms

  • Adrenergic beta-Antagonists / therapeutic use
  • Aged
  • Aged, 80 and over
  • Angiotensin Receptor Antagonists / therapeutic use
  • Angiotensin-Converting Enzyme Inhibitors* / therapeutic use
  • Antihypertensive Agents / therapeutic use
  • Blood Pressure / drug effects
  • Cross-Sectional Studies
  • Drug Therapy, Combination
  • Female
  • Hospital Mortality*
  • Humans
  • Hypertension / drug therapy
  • Hypertension / mortality
  • Hypertension / physiopathology
  • Ischemic Stroke* / blood
  • Ischemic Stroke* / diagnosis
  • Ischemic Stroke* / drug therapy
  • Ischemic Stroke* / mortality
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Renin-Angiotensin System* / drug effects
  • Risk Assessment
  • Risk Factors
  • Time Factors
  • Treatment Outcome

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Antihypertensive Agents
  • Adrenergic beta-Antagonists
  • Angiotensin Receptor Antagonists