Bleeding risk associated with the co-use of direct oral anticoagulants and non-dihydropyridine calcium channel blockers: a meta-analysis.

BACKGROUND

Oral anticoagulation is a cornerstone of stroke prevention in patients with atrial fibrillation (AF) and elevated thromboembolic risk. However, evidence regarding the association between co-use of direct oral anticoagulants (DOACs) and non-dihydropyridine calcium-channel blockers (CCBs) and bleeding risk remains controversial.

METHODS

We systematically searched PubMed, Embase, and the Cochrane Library for randomized clinical trials, cohort, and case-control studies evaluating bleeding risk associated with DOAC + CCB co-use in patients with AF. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for binary outcomes.

RESULTS

Nine studies met inclusion criteria, comprising 408,276 patients overall, of whom 67,359 were using DOACs + CCBs. Meta-analysis showed a significantly higher incidence of major bleeding with DOAC + CCB co-use compared with DOAC alone (OR 1.21 [95% CI 1.18-1.43]; p < 0.001; I2 = 21%). By contrast, there was no significant difference in any bleeding events between groups (OR 1.21 [95% CI 0.83-1.77]; p = 0.31; I2 = 77%).

CONCLUSION

Co-use of DOACs and non-dihydropyridine CCBs is associated with an increased risk of major bleeding, whereas the overall risk of any bleeding does not differ significantly. Large randomized controlled trials are warranted to confirm these findings and to further evaluate the safety of this combination.