Analysis of Upper Gastrointestinal Adverse Events Associated with Oral Anticoagulants and Potential Drug Interactions with Cardiovascular Drugs: Exploratory Study Using FDA Adverse Event Reporting System.

Background

This study aimed to evaluate the risk of upper gastrointestinal (UGI) adverse events (AEs) associated with oral anticoagulants (OACs) and identify potential interactions with cardiovascular (CV) drugs.

Methods

Individual case safety reports (ICSRs) from the FDA Adverse Event Reporting System from July 2014 to December 2023 were analyzed. Dataset I was constructed to assess the associations between OACs and UGI AEs using disproportionality analysis. Dataset Ⅱ included OAC-related ICSRs to explore potential interactions with CV drugs through logistic regression. Positive signals were defined as potential associations identified by disproportionality analysis metrics, such as reporting odds ratios (RORs) or adjusted RORs (aRORs) accounting for confounders.

Results

Dataset I included 12,905,290 ICSRs, and a positive signal for dabigatran was detected with an ROR of 1.19 (95% CI, 1.13-1.25). A total of 364,044 OAC-related ICSRs were included in dataset II. At the pharmacologic drug class level, several positive signals were identified, represented as aRORs with 95% CIs: for warfarin, amiodarone analogs (1.22; 1.04-1.43); for apixaban, angiotensin-converting enzyme inhibitors (1.34; 1.24-1.45), angiotensin receptor blockers (1.23; 1.14-1.33), dihydropyridine calcium channel blockers (1.30; 1.21-1.41), and digitalis glycosides (1.72; 1.49-2.00); and for edoxaban, angiotensin receptor blockers (1.88; 1.48-2.37), amiodarone analogs (1.73; 1.06-2.85), and anti-platelets (1.56; 1.20-2.03). No signals were observed for rivaroxaban or dabigatran. At the individual drug level, 62 OAC-CV pairs were identified as having potential interactions.

Conclusions

Drug-specific interaction profiles should be considered to ensure safe and personalized use of OACs in clinical practice.