Concomitant diltiazem use with DOACs pose increased bleeding risk in AF

Taking diltiazem and direct oral anticoagulants (DOACs) together appears to contribute to increased bleeding risk in patients with atrial fibrillation (AF), regardless of the presence of chronic kidney disease (CKD), as shown in a study.

Researchers looked at 4,544 AF patients who were initiated on rivaroxaban (n=1,583), apixaban (n=2,373), or dabigatran (n=5,88). Their mean age was 72 years, and 45 percent were women. The average baseline estimated glomerular filtration rate (eGFR) was 70 mL/min per 1.73 m², average CHA₂DS₂‐VASc score was 3.8, and average HAS‐BLED score was 3.2. Most patients had a history of stroke, coronary heart disease, or peripheral vascular disease; half had a bleeding history.

At the time of DOAC initiation, 15 percent of the patients were on diltiazem, and an additional 5 percent (203 of 3,862) initiated diltiazem subsequently during follow‐up (median 58 days). Patients who used diltiazem were younger and more likely to be women and healthier (higher eGFR, lower CHA₂DS₂‐VASc score, lower HAS‐BLED score, and fewer comorbidities).

Compared with use of DOACs alone, concurrent use of diltiazem was associated with a 1.5-fold increase in the risks of any bleeding‐related hospitalization (unadjusted risk difference, 2.4 events per 100 person‐years; adjusted hazard ratio [aHR], 1.56, 95 percent confidence interval [CI], 1.15–2.12) and major bleeding (unadjusted risk difference, 1.4 events per 100 person‐years; aHR, 1.84, 95 percent CI, 1.18–2.85).

The risk increase with concurrent diltiazem use was observed in both patients with and without CKD (p=0.524 and p=0.629, respectively).

Among the 13,179 patients who used warfarin (negative control), concomitant diltiazem had a null effect on bleeding risk.