Review article: Risk of cardiovascular events in patients with inflammatory bowel disease receiving small molecule drugs

Aliment Pharmacol Ther. 2023 Jun;57(11):1231-1248. doi: 10.1111/apt.17509.Epub 2023 Apr 10.


Pablo A Olivera 1 2Juan S Lasa 1 3Giovanni Peretto 4 5Stephane Zuily 6Silvio Danese 7Laurent Peyrin-Biroulet 8


Author information

1IBD Unit, Gastroenterology Section, Department of Internal Medicine, Centro de Educación Médica e Investigación Clínica (CEMIC), Buenos Aires, Argentina.

2Zane Cohen Centre for Digestive Diseases, Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Ontario, Canada.

3Gastroenterology Department, Hospital Británico de Buenos Aires, Buenos Aires, Argentina.

4Myocarditis Disease Unit, Department of Cardiac Electrophysiology and Arrhythmology, IRCCS San Raffaele Scientific Institute, Milan, Italy.

5School of Medicine, Vita-Salute San Raffaele University, Milan, Italy.

6Vascular Medicine Division and Regional Competence Center for Rare Auto-Immune Diseases, Université de Lorraine, INSERM, DCAC and CHRU-Nancy, Nancy, France.

7Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital and Vita-Salute San Raffaele University, Milan, Italy.

8INSERM NGERE and Department of Hepatogastroenterology, Nancy University Hospital, Lorraine University, Vandoeuvre-lés-Nancy, France.


Background: In the context of an ageing inflammatory bowel disease (IBD) population, cardiovascular comorbidities become particularly relevant. Novel small molecule drugs (SMDs) for the treatment of moderate-to-severe IBD have been recently approved, including Janus kinase (JAK) inhibitors and sphingosine-1-phosphate receptor (S1P) modulators. Data from rheumatoid arthritis population have raised concerns about the risk of cardiovascular events with the use of tofacitinib, which was extrapolated to other immune-mediated diseases and other JAK inhibitors. S1P receptor modulation has been associated with potential cardiovascular events, especially bradycardia and cardiac conduction abnormalities.

Aim: To review the incidence of cardiovascular events with the use of SMDs in patients with IBD and to provide practical recommendations on mitigation strategies.

Methods: Published literature was reviewed; recommendations were synthesised by experts in both cardiovascular diseases and IBD.

Results: Evidence from the IBD population does not indicate a higher risk of cardiovascular events with tofacitinib and other JAK inhibitors. The risk is higher in patients with intermediate to high cardiovascular risk. S1P modulators may be associated with a dose-dependent, first-dose effect, transient risk of conduction abnormalities (bradycardia and AV block). Screening and monitoring of cardiovascular risk factors should be done in all patients with IBD. Risk stratification for cardiovascular disease should be performed before starting treatment with SMDs.

Conclusions: Available evidence of both JAK inhibitors and S1P modulators indicates a reassuring safety profile of SMDs from the cardiovascular perspective in the overall IBD population. Efforts should be made to identify patients with IBD at a higher risk of cardiovascular events.


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