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Abstract: PO2378

Risk of Bleeding Associated with Direct Oral Anticoagulants Is Higher Among Patients with Concomitant Use of Diltiazem in Patients with and without CKD

Session Information

Category: CKD (Non-Dialysis)

  • 2102 CKD (Non-Dialysis): Clinical, Outcomes, and Trials

Authors

  • Xu, Yunwen, Johns Hopkins University, Baltimore, Maryland, United States
  • Chang, Alex R., Geisinger Health, Danville, Pennsylvania, United States
  • Inker, Lesley Ann, Tufts Medical Center, Boston, Massachusetts, United States
  • McAdams-DeMarco, Mara, Johns Hopkins University, Baltimore, Maryland, United States
  • Grams, Morgan, Johns Hopkins University, Baltimore, Maryland, United States
  • Shin, Jung-Im, Johns Hopkins University, Baltimore, Maryland, United States
Background

Inhibitors of the cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp) systems can increase blood levels of direct oral anticoagulants (DOACs). Diltiazem, a moderate CYP3A4/P-gp inhibitor, is commonly used for heart rate control in patients with atrial fibrillation (AF). We hypothesized that the co-administration of diltiazem with DOACs would be associated with bleeding events, particularly in patients with CKD.

Methods

We identified adult patients with AF and without end-stage kidney disease in the Geisinger Health System who initiated any DOAC between 2010-2018. We used Cox proportional hazard models with time-varying exposure to diltiazem, adjusting for characteristics at DOAC initiation as well as time-varying eGFR and use of antiplatelets and nonsteroidal anti-inflammatory drugs. We examined whether the risk of bleeding differed by CKD (eGFR <60 ml/min/1.73 m2) status. As a negative control, we repeated the same analysis among warfarin users (n=13179), since there is no known interaction between warfarin and diltiazem.

Results

Among the 4544 patients who initiated apixaban (n=2373), rivaroxaban (n=1583), or dabigatran (n=588), the mean (SD) age was 72 (12) years, 45% were female, and the average eGFR was 69 (21) mL/min/1.73 m2. At the time of DOAC initiation, 15% were on diltiazem and additional 4% initiated diltiazem during the follow-up. Among DOAC users, concomitant use of diltiazem was associated with a higher risk of bleeding (hazard ratio, 1.64; 95% confidence interval [CI]: 1.20-2.24), consistently across CKD status (Figure A). Among warfarin users (the negative control), concomitant use of diltiazem was not associated with bleeding (Figure B).

Conclusion

Concomitant use of diltiazem with DOACs was associated with a higher risk of bleeding in patients with AF, with similar risk with and without CKD.

Funding

  • NIDDK Support