The Risk for Bleeding in Patients With Atrial Fibrillation From Concomitant Use of Apixaban or Rivaroxaban With Diltiazem Compared With Metoprolol.

BACKGROUND

Diltiazem is a potent inhibitor of cytochrome P450 3A4 and P-glycoprotein substrates, which can affect the metabolic pathways of factor Xa inhibitors, predisposing patients with atrial fibrillation (AF) to serious bleeding complications.

OBJECTIVE

To compare the risk for bleeding among patients with AF who used apixaban or rivaroxaban in combination with diltiazem compared with metoprolol.

DESIGN

Retrospective cohort active comparator study.

SETTING

U.S. administrative health care database.

PATIENTS: Persons with AF.

INTERVENTION: Use of apixaban or rivaroxaban with diltiazem or metoprolol.

MEASUREMENTS: The primary study outcome was a composite of serious bleeding events leading to hospitalization. Secondary study outcomes included composites of stroke or systemic embolism. Diltiazem was stratified by high dose (>120 mg/d) and low dose (≤120 mg/d). Propensity score matching was used to adjust for differences between diltiazem and metoprolol users.

RESULTS

In the matched cohort of patients with AF, 23 000 were users of diltiazem and 23 000 were users of metoprolol. After propensity score matching, diltiazem (vs. metoprolol) was associated with a higher risk for bleeding events (rate difference [RD], 5.4 [95% CI, 1.2 to 9.6] per 1000 person-years). The risk for bleeding increased with high- versus low-dose diltiazem (high dose: RD, 9.2 [CI, 2.7 to 15.7]; low dose: RD, 2.6 [CI, 0.5 to 8.0]). The estimated 12- and 6-month risk differences between diltiazem and metoprolol were 0.48 percentage points (CI, 0.09 to 0.83 percentage points) and 0.31 percentage points (CI, 0.04 to 0.58 percentage points), respectively.

LIMITATION: Residual confounding.

CONCLUSION

In commercially insured patients with AF receiving apixaban or rivaroxaban, the use of diltiazem was associated with an increased risk for serious bleeding complications when compared with metoprolol.

PRIMARY FUNDING SOURCE: National Heart, Lung, and Blood Institute.