Patients prescribed non-vitamin K oral anticoagulants (NOACs) to manage symptoms of atrial fibrillation (AFib) could be at increased risk for major bleeding if they are taking certain common medications at the same time, a study published in the Journal of the American Medical Association states.

NOACs are used more frequently now than ever before due to their easy administration and efficacy over warfarin, corresponding author Chang-Fu Kuo, MD, PhD, and co-authors wrote in the study. Still, AFib patients are subject to bleeding risks, even more so when they deal with multiple morbidities, high-risk medications and polypharmacy.

Kuo’s team analyzed data from the Taiwan National Health Insurance database, focusing on 91,330 patients with nonvalvular atrial fibrillation who were prescribed at least one NOAC between January 2012 and December 2016. The researchers then evaluated how a handful of other drugs—atorvastatin, digoxin, verapamil, ketoconazole and erythromycin, to name a few—affected the patients already taking NOACs.

The average age of the study population was 75, with the majority—54,006 patients—taking the NOAC rivaroxaban. Other patients were on a regimen of dabigatran (45,347) or apixaban (12,886). The most common medications prescribed alongside NOACs were atorvastatin, diltiazem, digoxin and amiodarone.

Kuo and colleagues found that when taken with NOACs, amiodarone, fluconazole, rifampin and phenytoin were the most problematic, resulting in a significant increase in incident rates of major bleeding. The least harmful drugs, which actually lowered bleeding risks, proved to be verapamil, diltiazem, cyclosporine, ketoconazole, itraconazole, voriconazole and dronedarone, the doctors reported.

The 12 concurrent medications analyzed in Kuo’s study might not be recommended by American Heart Association guidelines, the study stated, but they’re commonly required drugs for NOAC users in clinical scenarios. In addition, most of the knowledge we have of these drug interactions come from case reports or animal studies, the authors wrote.

Next steps could include prompt or real-time postmarket monitoring on drug combos, Kuo and co-authors wrote, and it’s possible to systematically and automatically monitor the safety profiles of new drugs. It could be helpful to combine a pharmacology database of drug-drug interactions with a clinical database, they wrote.

In the meantime, Kuo’s team suggested, physicians should consider potential risks associated with prescribing NOACs to AFib patients in concurrence with other drugs.