Association of hydrophilic versus lipophilic angiotensin-converting enzyme inhibitor use on pneumonia-related mortality

BACKGROUND: Recent studies suggest that angiotensin-converting enzyme (ACE) inhibitors may have beneficial effects for patients with or at risk for pneumonia. However, other studies have not found a survival benefit. Other research suggests that ACE inhibitors that are lipophilic may be superior to hydrophilic ACE inhibitors in terms of tissue penetration and inhibition of ACE. Our aim was to examine the associations of prior outpatient use of lipophilic and hydrophilic ACE inhibitors on mortality for patients hospitalized with community-acquired pneumonia. METHODS: A retrospective cohort study of subjects hospitalized with pneumonia at 2 tertiary teaching hospitals. We examined whether the prior outpatient use of hydrophilic or lipophilic ACE inhibitors was associated with 30-day mortality in a logistic regression analysis that adjusted for potential confounders using a propensity score. RESULTS: Data were abstracted on 787 subjects at the 2 hospitals. In our cohort, 24% (n = 186) were on ACE inhibitors at presentation: 111 lipophilic and 74 hydrophilic. Mortality was 9.2% at 30 days. In the multivariable model, lipophilic ACE inhibitor use (odds ratio 0.3, 95% confidence interval 0.1-0.8), but not hydrophilic ACE inhibitor use (0.7, 0.3-1.7), was significantly associated with 30-day mortality. CONCLUSIONS: Our study suggests that future research of ACE inhibitors in pneumonia must describe the specific medications received. Confirmatory studies are needed, as well as research to determine the mechanism(s) of this protective effect.