Impact of Angiotensin II Signaling Blockade on Clinical Outcomes in Patients with Inflammatory Bowel Disease

Abstract

Background: Preclinical data demonstrates that activation of the renin-angiotensin system (RAS) contributes to mucosal inflammation, and RAS inhibition by angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) improves colitis in animal models. Less is known regarding the effects of RAS inhibition on clinical outcomes in inflammatory bowel disease (IBD) patients. Aims: Evaluate the impact of ACEI and ARB on clinical outcomes in IBD. Methods: Rates of IBD-related hospitalizations, operations, and corticosteroid use were evaluated retrospectively in two groups. First, 111 IBD patients taking an ACEI or ARB were compared to non-users matched 1:1 based on sex, age, diagnosis, disease location, and hypertension diagnosis. Second, outcomes in a cohort of 130 IBD were compared prior to and during ACEI/ARB exposure. Results: Compared to matched controls, all IBD patients taken together with ACEI/ARB exposure had fewer hospitalizations (OR 0.26, p < 0.01), operations (OR 0.08, p = 0.02), and corticosteroid prescriptions (OR 0.5, p = 0.01). Comparing outcomes before and during ACEI/ARB use, there were no differences in hospitalizations, operations, or corticosteroid use for all IBD patients together, patients with UC had increased hospitalizations (0.08 pre-vs 0.16 during ACEI/ARB exposure, p = 0.03) but decreased corticosteroid use (0.24 pre-vs 0.12 during ACEI/ARB exposure, p < 0.01) during ACEI/ARB use. Conclusions: IBD patients with ACEI/ARB exposure had fewer hospitalizations, operations, and corticosteroid use compared to matched controls, although no differences in outcomes were

Identification of differentially expressed genes between the colon and ileum of patients with inflammatory bowel disease by gene co-expression analysis

“…31 In patients with IBD who are inhibited by angiotensin, hospitalization, surgery, and corticosteroid use are less frequent. 32 In the present study, of the 19 hub genes, ACE2 is the main component of the renin-angiotensin system. We found that expression of ACE2 was higher in the colon than in the ileum of patients with IBD.…”

Effect of ACE inhibitors and angiotensin II receptor blockers on disease outcomes in inflammatory bowel disease

“…Although our study demonstrated that rates of adverse disease activity outcomes were generally lower in patients with IBD prescribed ACE-I or ARB therapy, the results were less striking than those of previous smaller studies. [1,7] It may be that longer follow-up in this cohort of patients will provide more conclusive evidence that these drugs have a beneficial effect on the natural history of IBD.…”

Angiotensin II inhibits P‐glycoprotein in intestinal epithelial cells

“…In addition, the endothelial junctions of the blood vessels at the site of inflammation are more dilated resulting in a leaky vasculature allowing access of macromolecules to the basolateral surface. Thus, we believe that targeting angiotensin II type 1 receptors (ATR1) located at the basolateral surface by ATR1 blockers (ARBs) would be beneficial in treating IBD by attenuating the angiotensin II‐mediated inhibition of Pgp. Thus, modulation of Pgp (MDR1) by Ang II/ATR1 appears to be a novel potential target for the treatment of gut inflammatory disorders including IBD.…”