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Use of diltiazem along with anticoagulants (apixaban or rivaroxaban) in patients aged 65 years or older with atrial fibrillation (AF) was associated with a higher risk of serious bleeding than metoprolol, a study has found.
The retrospective cohort study, published on 15 April 2024 in The Journal of the American Medical Association, included data from 204,155 Medicare beneficiaries in the United States, who filled a prescription for apixaban or rivaroxaban between January 2012 and November 2020.
Participants were included in the study cohort if they also filled prescriptions for diltiazem or metoprolol during this time. The mean age of study participants was 76.9 years. Diltiazem, a calcium channel blocker was prescribed in 53,275 patients and metoprolol, a beta blocker, in 150,880 patients.
The primary composite outcome consisted of bleeding-related hospitalisation or death with recent evidence of bleeding.
Researchers found that patients receiving diltiazem had an increased risk of the primary outcome (hazard ratio [HR]: 1.21 (95% confidence interval [CI]) compared with patients receiving metoprolol.
Bleeding risk associated with diltiazem was also increased with initial diltiazem dose — patients treated with 120mg/day (HR 1.13 [95% CI]) versus patients treated with doses higher than 120mg/day (HR 1.29 [95% CI]).
Commenting on the study, Anna Man, lead pharmacist for clinical and cardiothoracic services at Mid and South Essex NHS Foundation Trust, said: “Currently, dose adjustment is not advised with the combination of diltiazem, an inhibitor of CYP3A4, and apixaban.
“This study has provided insight of the extent of this interaction and the adverse effects in elderly patients taking high doses of diltiazem (>120mg/day).
“Drug–drug interactions are typically based on small cohort or case reports. This large study will have an impact on how we monitor and educate our patients to report bleeding. The dose-related element is also useful to help guide us on who are more at risk,” said Man.
“The recently reported incident of warfarin and tramadol co-administration highlight the importance to be vigilant of under-recognised interactions,” she added.
In December 2023, a prevention of future deaths report was issued following the death of a patient owing to the “result of a generally unknown interaction between warfarin and tramadol”.
In response to the coroner’s report, the warfarin–tramadol interaction was included in the British National Formulary from January 2024.
