Abstract
Background: Existing research suggests a potential increase in bleeding risk associated with the combined use of calcium channel blockers (CCBs) and direct oral anticoagulants (DOACs). However, the evidence remains inconclusive and conflicting. To clarify this relationship, we conducted a meta-analysis to investigate the risk of major bleeding in patients with atrial fibrillation (AF) using diltiazem. Methods: We conducted a comprehensive search of major electronic databases, including PubMed, Embase, and the Cochrane Library, from their inception through April 20, 2024 for relevant studies. The primary endpoint was major bleeding, defined as a composite of bleeding-related hospitalization, requiring blood transfusion, or fatal bleeding. We conducted a conventional meta-analysis using the Hartung-Knapp-Sidik-Jonkman random-effects model. Endpoints are expressed as hazard ratio (HR) and their corresponding confidence intervals (CI). Results: A total of 5 studies with 488,884 patients with AF were included in our study, of which 23.4% of patients were on diltiazem. All patients were also on DOACs. Results of the meta-analysis showed that there was no statistically significant difference between use of diltiazem and the risk of major bleeding (HR 1.16 ; 95% CI 0.94-1.42). Sensitivity analysis showed that this result remained unaltered in terms of magnitude and direction after excluding one study at a time. When stratified by type of control group, both active comparator (HR 1.09 ; 95% CI 0.92-1.30) and non-use subgroups (HR 1.24 ; 95% CI 0.87-1.77) showed that there was no significant difference in the risk of major bleeding with diltiazem use respectively. Conclusion: We observed that there was no significant difference in the risk of major bleeding in diltiazem use compared to controls in AF patients on DOACs. Further large-scale, longitudinal, and prospective studies are essential to validate these findings.
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