Effects of age, sex, daily dose, comorbidity and co‐medication on venlafaxine‐associated cardiovascular adverse events: A pharmacovigilance analysis of the FDA Adverse Event Reporting System database

Abstract Aims This study aimed to provide a comprehensive view of cardiovascular adverse events (AEs) associated with venlafaxine (VEN) therapy. Methods Cardiovascular AE reports for patients receiving VEN therapy were retrieved from January 2004 to December 2023 from the FDA Adverse Event Reporting System database. Effects of age, sex and daily VEN dose on the occurrence of different types of cardiovascular AEs and the influence of demographics, VEN dose, comorbidity and co‐medication on death in patients with cardiovascular AEs were analysed by multivariate logistic regression analysis. Results The study included 16 110 AE reports following VEN treatment (median age: 51 years, females: 69.78%, median VEN daily dose: 100 mg/day). VEN daily dose was associated with increased risks of cardiac arrhythmias, embolic and thrombotic events, torsade de pointes/QT prolongation, ischaemic heart disease, cardiac failure, cardiomyopathy and overall cardiovascular events. The elderly (≥ 75 years), male sex, comorbidity (infections and infestations, cardiac disorders, nervous system disorders) and co‐medication (quetiapine and clozapine) were related to death following VEN‐associated cardiovascular AEs; however, the risk of cardiovascular death did not increase with regular VEN doses. Conclusions Our study confirmed the association of cardiovascular AEs with VEN therapy and revealed the influencing factors for the risk of VEN‐related cardiovascular AEs and death due to these events. Based on the obtained evidence, the cardiovascular health of late‐elderly patients with complex comorbidity and polytherapy should be closely monitored when they receive VEN therapy. As an exploratory study, prospective studies are needed to validate our findings in the future.