Diltiazem use tied to serious bleeding risk in atrial fibrillation patients on apixaban or rivaroxaban: JAMA

"In the cohort study of 204 155 patients aged 65 years or older, those treated with diltiazem had a significantly higher risk of serious bleeding compared with those treated with metoprolol," the researchers reported.

Atrial fibrillation is a common cardiac arrhythmia characterized by irregular heartbeats, which can increase the risk of stroke due to the formation of blood clots in the atria. To mitigate this risk, anticoagulant therapy is often prescribed. Two widely used anticoagulants for AF are apixaban and rivaroxaban. However, when AF patients on these anticoagulants experience serious bleeding, particularly while also taking diltiazem, managing the situation becomes complex.

Diltiazem is a commonly prescribed ventricular rate–control medication for AF patients, inhibits apixaban and rivaroxaban elimination, possibly causing over-anticoagulation.

Against the above background, Wayne A. Ray, Vanderbilt University School of Medicine, Nashville, Tennessee, and colleagues aimed to compare serious bleeding risk for new users of rivaroxaban or apixaban with atrial fibrillation treated with diltiazem or metoprolol.

For this purpose, the researchers conducted a retrospective cohort study including Medicare beneficiaries aged 65 years or older with AF who initiated rivaroxaban or apixaban use and began treatment with metoprolol or diltiazem between 2012 and 2020. Patients were followed for 365 days.

A total of 204 155 US Medicare beneficiaries were included, of whom 53 275 received diltiazem and 150 880 received metoprolol. Study patients (mean age, 76.9 years; 52.7% female) had 90 927 person-years (PY) of follow-up (median, 120 days).

The study's primary outcome was a composite of bleeding-related hospitalization and death with recent evidence of bleeding. Secondary outcomes included major ischemic or hemorrhagic events (ischemic stroke, intracranial or fatal extracranial bleeding, systemic embolism, or death with recent evidence of bleeding), systemic embolism or ischemic stroke, and death without recent evidence of bleeding.

Hazard ratios (HRs) and rate differences (RDs) were adjusted for covariate differences with overlap.

Following were the study’s key findings:

• Patients receiving diltiazem treatment had increased risk for the primary outcome (RD, 10.6 per 1000 PY; HR, 1.21) and its components of bleeding-related hospitalization (RD, 8.2 per 1000 PY; HR, 1.22) and death with recent evidence of bleeding (RD, 2.4 per 1000 PY; HR, 1.19) compared with patients receiving metoprolol.
• The risk for the primary outcome with initial diltiazem doses exceeding 120 mg/d (RD, 15.1 per 1000 PY; HR, 1.29) was greater than that for lower doses (RD, 6.7 per 1000 PY; HR, 1.13).
• For doses exceeding 120 mg/d, the risk of major ischemic or hemorrhagic events was increased (HR, 1.14).
• Neither dose group had significant changes in the risk for ischemic stroke or systemic embolism, or death without recent evidence of bleeding.
• When patients receiving high- and low-dose diltiazem treatment were directly compared, the HR for the primary outcome was 1.14.

"Diltiazem was associated with a greater risk of serious bleeding than metoprolol, particularly for diltiazem doses exceeding 120 mg/d in Medicare patients with atrial fibrillation receiving apixaban or rivaroxaban," the researchers concluded.

Reference:

Ray WA, Chung CP, Stein CM, et al. Serious Bleeding in Patients With Atrial Fibrillation Using Diltiazem With Apixaban or Rivaroxaban. JAMA. Published online April 15, 2024. doi:10.1001/jama.2024.3867