C0409 - The Effect of Commonly Prescribed Renin-Angiotensin-Aldosterone System Blocking Agents on the 5- and 10-year Disease Course of Crohn’s Disease Patients With Hypertension

Monday, October 24, 2022

3:00 PM – 5:00 PM ET

Location: Crown Ballroom

Has Audio

Presenting Author(s)

Christian Karime, MD

Mayo Clinic
Jacksonville, FL

Christian Karime, MD¹, Jana G. Hashash, MD, MSc¹, Michael F. Picco, MD, PhD¹, Joseph A. Murray, MD², Francis A. Farraye, MD, MSc³
¹Mayo Clinic Florida, Jacksonville, FL; ²Mayo Clinic Rochester, Rochester, MN; ³Mayo Clinic, Jacksonville, FL

Introduction: Activation of the renin-angiotensin-aldosterone system (RAAS) has been associated with gastrointestinal inflammation and fibrosis, suggesting that blockade may be beneficial in patients with inflammatory bowel disease (IBD). Using retrospective analysis, we aimed to compare the disease course of Crohn’s disease (CD) patients initiated on two commonly prescribed classes of RAAS-blocking agents.

Methods: Patients with CD and hypertension who were initiated on an angiotensin-converting-enzyme inhibitor (ACEI, n=40) or angiotensin-receptor blocker (ARB, n=40) between 2000-2016 were included. A control group (n=40) was created and matched on gender, body mass index, CD Montreal classification, age at CD diagnosis, CD duration, and common comorbid conditions. Data was collected on surrogate markers of IBD severity in the 3-, 5-, and 10-years following ACEI or ARB initiation. Surrogate markers included clinical (emergency department visits, hospitalizations, corticosteroid use, and biologic therapy use), radiological (computer tomography [CT], CT enterography, magnetic resonance imaging, magnetic resonance enterography), and procedural (endoscopic procedures, IBD-related operations) variables. Statistical analysis was performed by one-way multivariate analysis of variance with Tukey post-hoc testing.

Results: Compared to control, patients taking ARBs had fewer instances of systemic corticosteroid use (1.06 vs.2.88, p< 0.01, -63%) at the 10-year interval. On the other hand, patients taking ACEIs had an overall worse disease course, with more imaging studies (3.00 vs.1.75, p=0.03, +71%) and endoscopic procedures (2.70 vs. 1.78, p=0.01, +52%) at 5-years, and more imaging studies (6.19 vs.3.50, p< 0.01, +77%), endoscopic procedures (5.91 vs.3.78, p< 0.01, +56%), and IBD-related operations (0.59 vs.0.18, p< 0.02, +228%) at 10-years. ACEI-treated patients were also more likely to initiate biologic therapy compared to control (56.0% vs.32.3%) and ARB-treated patients (56.0% vs.17.4%).

Discussion: Our study provides insight into the long-term use of RAAS-blocking agents in patients with CD, suggesting that differences exist between commonly prescribed medication classes. While ACEIs were associated with an overall worse disease course at 5- and 10-years, patients taking ARBs were noted to have fewer instances of corticosteroid use at 10-years. Given the frequent use of ACEI and ARB therapy, future large-scale studies are needed to further explore the association RAAS-blockade and IBD disease course.

	Average number of events per patient
Variable	3 years				5 years				10 years
	CD-ACEI (n= 40)	CD-ARB (n= 40)	CD-Control (n= 40)	p-value	CD-ACEI (n= 40)	CD-ARB (n= 40)	CD-Control (n= 40)	p-value	CD-ACEI (n= 32)	CD- ARB (n= 33)	CD-Control (n= 40)	p-value
Emergency department visits (all)	1.25	1.50	1.90	0.33	2.52	2.30	2.60	0.87	5.34	3.91	6.1	0.10
Emergency department visits (abdominal pain)	0.58	0.48	0.48	0.87	1.05	0.60	0.75	0.29	2.34	0.91	1.70	< 0.02
Hospitalizations (abdominal pain)	0.18	0.15	0.25	0.72	0.38	0.23	0.28	0.56	0.88	0.30	0.65	0.07
Systemic corticosteroid use (single instances)	0.63	0.35	1.00	0.09	1.53	0.45	1.28	0.03	3.72	1.06	2.88	< 0.01
Abdominal imaging	2.05	1.55	1.25	0.12	3.00	1.83	1.75	< 0.02	6.19	2.73	3.50	< 0.01
Endoscopic procedures	1.45	0.90	1.05	0.12	2.70	1.60	1.78	< 0.01	5.91	2.61	3.78	< 0.01
Gastrointestinal operations	0.13	0.08	0.08	0.72	0.15	0.10	0.08	0.18	0.59	0.15	0.18	< 0.01

Table: Table 1: Summary of clinical, radiological, and procedural surrogate markers of inflammatory bowel disease severity in the 3-, 5-, and 10-years following initiation of renin-angiotensin-aldosterone system blocking therapy.
Values are expressed as average number of events per patient at 3-, 5-, and 10-years following initiation of either an angiotensin-converting-enzyme inhibitor (ACEI) or angiotensin-receptor blocker (ARB). In case of control patients, values represent the average number of events per patient at 3-, 5-, and 10-years following start of follow-up interval. Emergency department visits included all visits as well as visits with abdominal pain as the chief complaint. Hospitalization included only those with abdominal pain as the chief complaint. Systemic corticosteroid usage was defined as single instances of systemic corticosteroid therapy. Abdominal imaging was defined as imaging of the abdominal area with Crohn’s disease as the primary indication. Endoscopic procedures included colonoscopy, sigmoidoscopy, double balloon enteroscopy, esophagogastroduodenoscopy. Gastrointestinal operations were defined as operations with Crohn's disease as the primary indication (including colectomy, small bowel resection, ileocecectomy, and proctocolectomy).

ACEI: Angiotensin-converting-enzyme inhibitor, ARB: Angiotensin receptor blocker, CD: Crohn’s disease

Disclosures:

Christian Karime indicated no relevant financial relationships.

Jana Hashash indicated no relevant financial relationships.

Michael Picco indicated no relevant financial relationships.

Joseph Murray: Allakos – Grant/Research Support. Bionix – Consultant. Bristol Myers Squibb – Consultant. Chugai Pharma – Consultant. Cour – Grant/Research Support. Dr. Schar USA – Consultant. Dren Bio – Consultant. Evelo Biosciences – Intellectual Property/Patents. GSK – Consultant. Immunic – Consultant. Immunic – Consultant. Immunogenics – Grant/Research Support. Johnson & Johnson – Grant/Research Support. Kanyos/Anakion – Grant/Research Support. National Institutes of Health – Grant/Research Support. Nexpep/ImmusanT – Grant/Research Support. Oberkotter – Grant/Research Support. Takeda Pharmaceutical – Grant/Research Support. Torax Medical – Royalties. UKKO – Consultant.

Francis Farraye: Adiso Therapeutics – DSMB. BMS – Advisory Committee/Board Member. Braintree Labs – Advisory Committee/Board Member. GSK – Advisory Committee/Board Member. IBD Educational Group – Advisory Committee/Board Member. Innovation Pharmaceuticals – Stock Options. Iterative Scopes – Advisory Committee/Board Member. Janssen – Advisory Committee/Board Member. Lilly – DSMB. Pfizer – Advisory Committee/Board Member. Sebela – Advisory Committee/Board Member. Theravance – DSMB.

Christian Karime, MD¹, Jana G. Hashash, MD, MSc¹, Michael F. Picco, MD, PhD¹, Joseph A. Murray, MD², Francis A. Farraye, MD, MSc³. C0409 - The Effect of Commonly Prescribed Renin-Angiotensin-Aldosterone System Blocking Agents on the 5- and 10-year Disease Course of Crohn’s Disease Patients With Hypertension, ACG 2022 Annual Scientific Meeting Abstracts. Charlotte, NC: American College of Gastroenterology.