Effect of Renin-Angiotensin-Aldosterone System Inhibitors on Short-Term Mortality After Sepsis

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.

Is the use of RAS inhibitors safe in the current era of COVID-19 pandemic?

“…Because RAS blockade or beta blocker is recommended for the patient with cardiovascular complications, stopping these drugs may be harmful. In a recent retrospective population based cohort study, Hsu W, et al, reported that established RAS blockade therapy before sepsis will be protective for the sepsis related mortality [1]. These results seems to be in line with the recent study showing depressed sympathetic modulation can be a signal for sepsis in patient with infection [2].…”

Use of inhibitors of the renin‐angiotensin system in hypertensive patients and COVID‐19 severity: A systematic review and meta‐analysis

“…On the other hand, scientific societies recommend not to discontinue RAS inhibitors because of insufficient evidence of their potential harm and overwhelming evidence on their benefits 35‐39 and even some researchers advocate for the use of RAS inhibitors based on the fact that, through increasing the expression of ACE2, they counterbalance the reduction in pulmonary ACE2 provoked by the virus either through internalization with viral entry and/or downregulation of ACE2 enzyme during this process, which would lower the production of inflammatory cytokines, 40 thus exerting a protective role in lung injury 41 . Remarkably, RAS inhibitors have been shown to be associated with reduced mortality in patients with sepsis 42 . A study conducted by Henry C et al 43 have found a beneficial effect of ACEI/ARB in patients admitted with viral pneumonia, as they significantly reduced the pulmonary inflammatory response and cytokine release caused by virus infection.…”

Renin-angiotensin system inhibitors improve the clinical outcomes of COVID-19 patients with hypertension

“…The abnormal increase in Angiotensin II was related to hypertension and lung failure. In addition, RAS inhibitors have been shown to be associated with reduced mortality in patients with sepsis [9]. Angiotensin II positively regulates the expression of inflammatory cytokines through the activation of AT1R [10].…”