Background: Inflammatory bowel disease (IBD) is associated with an increased risk of Major Adverse Cardiovascular Events (MACE) due to underlying chronic inflammation. Decreasing the inflammatory burden may decrease this risk however certain medications used to treat IBD and cardiovascular (CV) risk factors are associated with an increased risk of MACE. We aim to determine the association between MACE and IBD medications in a large national cohort of patients with IBD.

Methods: We performed a retrospective analysis using the multi-institutional database TriNetX and assessed IBD patients (Ulcerative Colitis and Crohn’s Disease) between 2015-2023. We compared patients on various IBD therapies [non-advanced (prednisone, budesonide, 5-aminosalicylates), immunomodulators (IM), anti-TNF (infliximab, adalimumab, certolizumab, golimumab), anti-integrin (vedolizumab), anti-IL12/23 (ustekinumab, risankizumab), JAK inhibitors (tofacitinib, upadacitinib)] and statins for outcomes of myocardial infarction (MI), ischemic stroke, percutaneous coronary intervention (PCI)/coronary artery bypass graft (CABG), and composite MACE. Outcomes were assessed after the IBD index date. Patients with other chronic inflammatory disorders, celiac disease, and malignancy were excluded. Data on demographics, CV risk factors, and prior coronary artery disease (CAD) was collected at the time of IBD diagnosis. Python programming language with the statsmodels package was used to perform logistic regression and outcomes were adjusted for age, gender, CV risk factors, prior CAD, history of heart failure, anemia, non-advanced IBD therapy, IM, and statin use. A p-value of <0.05 was considered statistically significant.

Results: We identified 113,729 patients with IBD (Table 1). Most patients were young and had low rates of CV risk factors (5-6%) and statin use (6-10%) at the time of IBD diagnosis. Patients on anti-TNF were less likely to have MI, stroke, PCI/CABG, and composite MACE which was statistically significant after adjusting for variables for PCI/CABG [adjusted odds ratio [aOR] 0.56, p 0.002] and composite MACE [aOR 0.78, p 0.005] (Table 2). Patients on anti-integrins and anti-IL12/23 medications were less likely to have MI, stroke, PCI/CABG, and composite MACE with a significant risk reduction with anti-integrins for composite MACE [aOR of 0.76, p 0.035]. Patients on JAK inhibitors were less likely to have MI, stroke, PCI/CABG, and composite MACE. Results for the Sphingosine-1-phosphate (S1p) receptor modulator ozanimod were not included due to a small number of patients.

Conclusion: IBD patients treated with biologics and JAK inhibitors are less likely to have MACE with the most notable risk reduction seen with anti-TNF medications after adjusting for CV risk factors. Studies are needed to see whether this decrease in risk is due to control of the disease or mechanism of a drug.

Table 1: Demographic and risk factors for cardiovascular disease of patients with IBD on biologics and JAK inhibitors.

Table 2: Major adverse cardiovascular events (MACE) in IBD patients on various biologics and JAK inhibitors. Adjusted to age, gender, anemia CV risk factors, prior coronary artery disease, and heart failure.

Jake Luo

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