Patients with IBD requiring surgery over 2 years were significantly less likely to be treated with ACE inhibitors and ARBs compared to those not requiring surgery (2.7% vs 16.0%, p=0.034).
Observational
Does targeting the renin-angiotensin system with ACE inhibitors or ARBs reduce fibrosis and improve clinical outcomes in patients with inflammatory bowel disease?
The renin-angiotensin system is perturbed in IBD and mediates fibrosis, while treatment with ACE inhibitors or ARBs is associated with a reduced need for surgery and hospitalization.
Absolute Event Rate: 2.7% vs 16%
p-value: p=0.034
OBJECTIVE: We evaluated the influence of the renin-angiotensin system (RAS) on intestinal inflammation and fibrosis. DESIGN: Cultured human colonic myofibroblast proliferation and collagen secretion were assessed following treatment with angiotensin (Ang) II and Ang (1-7), their receptor antagonists candesartan and A779, and the ACE inhibitor captopril. Circulating and intestinal RAS components were evaluated in patients with and without IBD. Disease outcomes in patients with IBD treated with ACE inhibitors and angiotensin receptor blockers (ARBs) were assessed in retrospective studies. RESULTS: Human colonic myofibroblast proliferation was reduced by Ang (1-7) in a dose-dependent manner (p<0.05). Ang II marginally but not significantly increased proliferation, an effect reversed by candesartan (p<0.001). Colonic myofibroblast collagen secretion was reduced by Ang (1-7) (p<0.05) and captopril (p<0.001), and was increased by Ang II (p<0.001). Patients with IBD had higher circulating renin (mean 25.4 vs 18.6 mIU/L, p=0.026) and ACE2:ACE ratio (mean 0.92 vs 0.69, p=0.015) than controls without IBD. RAS gene transcripts and peptides were identified in healthy and diseased bowels. Colonic mucosal Masson's trichrome staining correlated with Ang II (r=0.346, p=0.010) and inversely with ACE2 activity (r=-0.373, p=0.006). Patients with IBD who required surgery (1/37 vs 12/75, p=0.034) and hospitalisation (0/34 vs 8/68, p=0.049) over 2 years were less often treated with ACE inhibitors and ARBs than patients not requiring surgery or hospitalisation. CONCLUSIONS: The RAS mediates fibrosis in human cell cultures, is expressed in the intestine and perturbed in intestinal inflammation, and agents targeting this system are associated with improved disease outcomes.
Garg et al. (2019) conducted an observational in Inflammatory Bowel Disease (IBD). ACE inhibitors and angiotensin receptor blockers (ARBs) vs. Patients not treated with ACE inhibitors and ARBs was evaluated on Treatment with ACE inhibitors and ARBs in patients requiring surgery vs not requiring surgery over 2 years (p=0.034). Patients with IBD requiring surgery over 2 years were significantly less likely to be treated with ACE inhibitors and ARBs compared to those not requiring surgery (2.7% vs 16.0%, p=0.034).
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