Effect of Renin-Angiotensin-Aldosterone System Inhibitors on Short-Term Mortality After Sepsis: A Population-Based Cohort Study

Abstract

Antagonists of the renin-angiotensin-aldosterone system (RAAS), including ACEIs (angiotensin-converting enzyme inhibitors) and ARBs (angiotensin II receptor blockers), may prevent organ failure. We, therefore, investigated whether specific RAAS inhibitors are associated with reduced mortality in patients with sepsis.We conducted a population-based retrospective cohort study using multivariable propensity score-based regression to control for differences among patients using different RAAS inhibitors. A multivariable-adjusted Cox proportional-hazards regression model was used to determine the association between RAAS inhibitors and sepsis outcomes. To directly compare ACEI users, ARB users, and nonusers, a 3-way propensity score matching approach was performed. Results were pooled with previous evidence via a random-effects meta-analysis. A total of 52 727 patients were hospitalized with sepsis, of whom 7642 were prescribed an ACEI and 4237 were prescribed an ARB. Using propensity score-matched analyses, prior ACEI use was associated with decreased 30-day mortality (hazard ratio, 0.84 [95% CI, 0.75-0.94]) and 90-day mortality (hazard ratio, 0.83 [95% CI, 0.75-0.92]) compared with nonuse. Prior ARB use was associated with an improved 90-day survival (hazard ratio, 0.88 [95% CI, 0.83-0.94]). These results persisted in sensitivity analyses focusing on patients without cancer and patients with hypertension. By contrast, no beneficial effect was found for antecedent β-blockers exposure (hazard ratio, 0.99 [95% CI, 0.94-1.05]). The pooled estimates obtained from the meta-analysis was 0.71 (95% CI, 0.58-0.87) for prior use of ACEI/ARB.The short-term mortality after sepsis was substantially lower among those who were already established on RAAS inhibitor treatment when sepsis occurred.

Keywords: angiotensin-converting enzyme inhibitor; hypertension; pharmacoepidemiology; propensity score; renin-angiotensin system; sepsis.