TOPLINE: 

Among patients with atrial fibrillation (AF) who initiated apixaban or rivaroxaban, the use of diltiazem was associated with a higher risk for serious bleeding complications than the use of metoprolol. The risk for bleeding was particularly elevated in patients who received diltiazem doses exceeding 120 mg daily.

METHODOLOGY:

• Researchers conducted a retrospective cohort study using data from over a 6-year period, starting in 2015, of adults with AF who initiated direct oral anticoagulant therapy (apixaban or rivaroxaban) with either diltiazem or metoprolol for rate control.
• They emulated a target trial to compare the safety and effectiveness of concomitant diltiazem vs metoprolol among new users of apixaban or rivaroxaban, with metoprolol serving as the active comparator. After propensity score matching, they included 23,000 users of diltiazem and 23,000 users of metoprolol (mean age for both, 64.1 years; 55% men).
• The primary outcome was serious bleeding-related hospitalization, identified using principal discharge diagnosis codes.
• Researchers stratified the initial diltiazem dosing into high dose (> 120 mg/d) and low dose (≤ 120 mg/d), with a median follow-up duration of 217 days for diltiazem users and 219 days for metoprolol users.

TAKEAWAY:

• Among the matched pairs, the use of diltiazem was associated with a higher risk for serious bleeding events than the use of metoprolol, with a rate difference of 5.4 events (95% CI, 1.2-9.6) per 1000 person-years. The higher risk for bleeding events was noted at 6 months (risk ratio [RR], 1.18; 95% CI, 1.03-1.35) and 12 months (RR, 1.18; 95% CI, 1.02-1.37).
• Bleeding risk increased with higher diltiazem doses, with doses > 120 mg/d vs metoprolol showing a rate difference of 9.2 events (95% CI, 2.7-15.7) per 1000 person-years.
• In the matched sample, rivaroxaban-diltiazem users experienced 38.5 serious bleeding events per 1000 person-years compared with 30 events among apixaban-diltiazem users, with an estimated risk difference of .64 percentage points.

IN PRACTICE:

"Our findings suggest the need for more caution about the possibility of bleeding in patients with AF who are using a DOAC [direct oral anticoagulant therapy] and diltiazem, especially when the diltiazem dose is greater than 120 mg/d," the authors of the study wrote.

SOURCE:

The study was led by Ghadeer K. Dawwas, PhD, MSc, MBA, of the Department of Medicine at the Vanderbilt University School of Medicine in Nashville. It was published online on February 24, 2026, in the Annals of Internal Medicine.

LIMITATIONS: 

Administrative claims databases did not provide information on over-the-counter medications, lifestyle factors, laboratory values, or measures of frailty. The study included patients with commercial or Medicare supplemental insurance, which may limit how well the findings apply to populations with only government coverage or those without insurance.

DISCLOSURES:

This study was supported by the National Heart, Lung, and Blood Institute. Various authors reported receiving authorship royalties, grants and gifts, and participation on a Data and Safety Monitoring Board, along with other organizations. All three authors reported being consultants for pharmaceutical companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.