Key result
Combining DOACs with diltiazem or verapamil increases major bleeding risk ~38% versus DOAC monotherapy.
Why the study?
Diltiazem and verapamil increase direct oral anticoagulant concentrations, but real-world studies evaluating bleeding and stroke risks with concomitant use have yielded contradictory findings.
Does the concomitant use of diltiazem or verapamil with DOACs increase the risk of major bleeding compared to DOAC monotherapy?
Meta-Analysis
Does the concomitant use of diltiazem or verapamil with DOACs increase the risk of major bleeding compared to DOAC monotherapy?
Concomitant use of diltiazem or verapamil with DOACs significantly increases the risk of major and gastrointestinal bleeding, highlighting the need for caution with this drug-drug interaction.
Answers are grounded in this paper and cite their sources.
Requires caution combining diltiazem or verapamil with DOACs; confirms elevated major bleeding risk in meta-analysis.
Background: Diltiazem and verapamil are combined p-glycoprotein and moderate CYP3A4 inhibitors which significantly increase the concentrations of direct oral anticoagulants (DOACs) and may increase the risks of bleeding. Multiple real-world studies compared the concomitant therapy of diltiazem/verapamil and DOACs versus the DOAC monotherapy groups, but their main findings were contradictory. Objective: To evaluate the risks of bleeding and stroke between the concomitant therapy of diltiazem/verapamil and DOACs and DOAC monotherapy. Methods: A meta-analysis was performed to compare the concomitant therapy of diltiazem/verapamil and DOACs versus DOACs. Database searches through November 16, 2024 were performed using MEDLINE and Google Scholar. The primary outcome was major bleeding. The secondary outcomes included stroke or systemic embolism and gastrointestinal bleeding. Results: A total of 6 studies were included in this meta-analysis. It showed that the concomitant therapy of DOAC and diltiazem/verapamil was significantly associated with increased risks of major bleeding (odds ratio [OR] = 1.38; 95% CI = 1.24, 1.54; P < 0.01; I 2 = 0%) and gastrointestinal bleeding (OR = 1.19; 95% CI = 1.03, 1.37; P = 0.01; I 2 = 0%) compared with the DOAC monotherapy group. The concomitant therapy group was also significantly associated with the lower risk of stroke or systemic embolism compared with the DOAC monotherapy group (OR = 0.83; 95% CI = 0.73, 0.93; I 2 = 0%). Conclusion and Relevance: This meta-analysis found that the concomitant therapy of DOACs with diltiazem/verapamil increases the risks of bleeding outcomes compared with the DOAC monotherapy group.
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Kido et al. (2025) conducted a meta-analysis in Patients taking DOACs. Concomitant therapy of diltiazem/verapamil and DOACs vs. DOAC monotherapy was evaluated on Major bleeding (OR 1.38, 95% CI 1.24, 1.54, p=< 0.01). Concomitant therapy of DOACs with diltiazem or verapamil significantly increased the risk of major bleeding compared with DOAC monotherapy (OR 1.38; 95% CI 1.24-1.54; P<0.01).
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