The Cardiovascular Effects of Inflammatory Bowel Disease Therapy with Biologics and Small Molecules: A Comprehensive Review

Abstract

Background/Objectives: Ιnflammatory bowel disease (IBD), comprising Crohn's disease (CD) and ulcerative colitis (UC), is increasingly associated with cardiovascular (CV) complications, such as heart failure (HF), arrhythmias, and acute coronary syndromes (ACSs). As the therapeutic landscape of IBD evolves, with the introduction of newer biologics and small molecules, their CV safety warrants critical evaluation. The objective of this review is to provide an update on the current evidence of CV risks associated with IBD treatments. Methods: A comprehensive literature search from inception to April 2025 was conducted using PubMed and Medline to identify randomized controlled trials, observational studies, systematic reviews, as well as pharmacovigilance data reporting CV safety outcomes of biologic and small-molecule drugs approved for IBD. Additionally, analysis of the European Summary of Product Characteristics for each agent was also performed. Results: Anti-TNF agents, particularly infliximab, have been associated with increased reporting of HF and arrhythmias, particularly in patients with pre-existing cardiac disease. Ustekinumab and vedolizumab show consistently favorable CV safety profiles across trials and real-world studies. IL-23p19 inhibitors demonstrate low CV event rates overall, although signals for atrial fibrillation have emerged with risankizumab. Janus kinase inhibitors and sphingosine-1-phosphate receptor modulators carry class-specific CV warnings, due to signals mainly on non-IBD populations, and require careful use in high-risk individuals. Conclusions: Although most IBD therapies are generally safe from a CV perspective, certain agents may pose risks in vulnerable patients. Individualized CV risk assessment and ongoing post-marketing surveillance are essential to guide therapeutic choices and ensure patient safety.

Keywords: acute coronary syndromes; arrhythmias; biologics; cardiovascular safety; heart failure; inflammatory bowel disease; small molecules.

Figure 1

Cardiovascular effects of IBD therapies. Anti-TNFs may increase the risk of heart failure (HF), JAK inhibitors are associated with major adverse cardiovascular events (MACE), and S1P modulators can cause bradycardia and conduction abnormalities. In contrast, IL-12/23, IL-23p19, and α4β7 integrin inhibitors may have neutral or even beneficial cardiovascular profiles, with IL-23p19 agents possibly providing anti-atherogenic effects.