Another Dangerous DOAC Drug Interaction

It’s not common for me to revisit a topic so soon after first covering it. Pharmacy Learning Network recently published a column discussing new data showing that the combination of amiodarone and rivaroxaban was potentially unsafe. In this installment of Talking Therapeutics, we explore another potentially dangerous direct-acting oral anticoagulant (DOAC) combination, this time with diltiazem.

Talking Point: Cause for Alarm With Multiple DOACs

Diltiazem is a moderate inhibitor of CPY3A4, which causes it to interact with many different drug classes, including DOACs. A recently published retrospective cohort study included over 200,000 patients with Medicare aged 65 years or older with atrial fibrillation (AFiB) who were treated with either apixaban or rivaroxaban and also began treatment with diltiazem or metoprolol. The primary outcome was a composite of bleeding-related hospitalization and death with recent evidence of bleeding.

Patients receiving diltiazem treatment had increased risk for the primary outcome (RHR, 1.21 [95% CI, 1.13-1.29]) and its components of bleeding-related hospitalization (HR, 1.22 [95% CI, 1.13-1.31]) and death with recent evidence of bleeding (1.19 [95% CI, 1.05-1.34]) compared with patients receiving metoprolol. Risk for the primary outcome was higher when the initial diltiazem doses exceeding 120 mg per day.

Talking Point: Time to Reconsider Diltiazem as First-Line Treatment

This study is much more serious than the study discussed in the recently published Pharmacy Learning Network column. Diltiazem is used much more commonly than amiodarone, and both most popularly prescribed DOACs are implicated. Diltiazem is considered to be a co-first-line drug with metoprolol for rate control in AFiB, assuming the patient doesn’t have heart failure with a reduced ejection fraction.

Given the bleeding risk highlighted in this new study, this position needs to be reconsidered. Beta-blockers should be elevated to first-line therapy for rate control, and diltiazem should be reserved for those with contraindications to beta-blockers.