Influence of Renin-Angiotensin System Inhibitors on Lower-Respiratory Tract Infections in Type 2 Diabetes: The Fremantle Diabetes Study Phase II.

Abstract

To determine whether ACE inhibitors (ACEi) and angiotensin receptor blockers (ARB) protect against lower-respiratory tract infections complicating type 2 diabetes. Of 1,732 participants with diabetes recruited to the longitudinal observational Fremantle Diabetes Study Phase II (FDS2) between 2008 and 2011, 1,482 had confirmed type 2 diabetes (mean age 65.8 years and median diabetes duration 9.0 years; 51.6% were male). All were followed for hospitalizations for or with, or deaths from, pneumonia/influenza, ascertained from validated administrative data linkage from study entry to end of 2016. Cox regression and competing risk regression were used to identify independent predictors of this outcome. Two-thirds of participants (<i>n</i> = 982) were taking an ACEi and/or ARB at study entry (498 [33.6%] ACEi, 408 [27.5%] ARB, 76 [5.1%] both). During 9,511 person-years of follow-up (mean ± SD 6.4 ± 2.0 years), 174 participants had incident pneumonia/influenza (156 hospitalizations and 18 deaths without hospitalization). In Cox regression analysis, baseline ACEi/ARB use was independently associated with a reduced risk of incident pneumonia/influenza (cause-specific hazard ratio [HR] 0.64 [95% CI 0.45, 0.89], <i>P</i> = 0.008). Allowing for the competing risk of death did not change this finding (subdistribution HR 0.67 [0.48, 0.95], <i>P</i> = 0.024), and similar reductions were seen for ACEi, ARB alone, and ACEi/ARB combination therapy. There was no significant change in use of ACEi/ARB during follow-up [interaction with ln(time), <i>P</i> = 0.70]. Other significant predictors of incident pneumonia/influenza were previously reported, clinically plausible variables. ACEi/ARB reduce the risk of pneumonia/influenza in people with type 2 diabetes.