In high-risk individuals, clinicians should weigh the potential for drug-drug interactions when prescribing diltiazem in combination with apixaban or rivaroxaban. (Vanderbilt Health file photo)
Patients with atrial fibrillation who are prescribed diltiazem to control heart rate alongside anticoagulants (blood thinners) such as apixaban or rivaroxaban face a higher risk of serious bleeding compared with those taking metoprolol, according to a new study from Vanderbilt Health researchers and colleagues at the Perelman School of Medicine.
While diltiazem is a commonly prescribed first-line agent for heart rate control in patients with atrial fibrillation, and apixaban and rivaroxaban are standard therapies for stroke prevention, their combination may present important safety concerns.
The Food and Drug Administration has previously identified drug-drug interactions mediated by cytochrome enzymes as a leading cause of preventable adverse events. Because diltiazem inhibits these enzymes, researchers sought to determine whether it increases the plasma concentrations of anticoagulants, thereby elevating the risk of major bleeding.
The current study, published Feb. 24 in the Annals of Internal Medicine, included 46,000 atrial fibrillation patients who had commercial health care coverage and used apixaban or rivaroxaban in combination with diltiazem or metoprolol.
“These findings are particularly important at the population level,” said Ghadeer Dawwas, PhD, MBA, assistant professor of Medicine and Health Policy at Vanderbilt. “Atrial fibrillation patients frequently have multiple comorbidities and are treated with several medications simultaneously. In high-risk individuals, clinicians should carefully weigh the potential for drug-drug interactions when prescribing diltiazem in combination with apixaban or rivaroxaban.”
“Although diltiazem remains an appropriate and effective option for heart rate control in selected patients, our results underscore that bleeding risk must be a central consideration in treatment decisions,” she added. “This is especially relevant for patients receiving higher doses exceeding 120 mg/day of diltiazem or those taking additional interacting medications. In such cases, metoprolol may represent a safer alternative.”
The research was supported by the National Heart, Lung, and Blood Institute (grant R00HL159230).
