Drugs may increase risk of bleeding with NOACs

Rivaroxaban

Concurrent use of non-vitamin K oral anticoagulants (NOACs) and drugs that share metabolic pathways with NOACs may affect the risk of major bleeding in patients with nonvalvular atrial fibrillation (NVAF), according to a study published in JAMA.

Researchers studied more than 91,000 Taiwanese patients with NVAF who were taking dabigatran, rivaroxaban, or apixaban.

Concurrent use of these NOACs with amiodarone, fluconazole, rifampin, or phenytoin was associated with a significant increase in major bleeding, when compared to use of NOACs alone.

On the other hand, major bleeding was significantly decreased for patients concurrently receiving NOACs and atorvastatin, digoxin, or erythromycin/clarithromycin.

Chang-Fu Kuo, MD, PhD, of Chang Gung Memorial Hospital in Taoyuan, Taiwan, and colleagues conducted this study.

The team used data from the Taiwan National Health Insurance database to study 91,330 patients with NVAF who received at least 1 NOAC prescription of dabigatran (n=45,347), rivaroxaban (n=54,006), or apixaban (n=12,886). The patients’ mean age was 74.7, and 55.8% were male.

The researchers estimated the bleeding risk associated with or without the concurrent use of commonly prescribed medications that share metabolic pathways with NOACs—atorvastatin, digoxin, verapamil, diltiazem, amiodarone, cyclosporine, rifampin, phenytoin, dronedarone, erythromycin/clarithromycin, fluconazole, and other azoles (ketoconazole, itraconazole, voriconazole, or posaconazole).

There were 4770 major bleeding events in the patient population.

The data showed that concurrent use of amiodarone, fluconazole, rifampin, and phenytoin with NOACs significantly increased the incidence rates of major bleeding. The adjusted incidence rates per 1000 person-years were:

• 38.09 for NOAC use alone vs 52.04 for amiodarone (difference=13.94, adjusted rate ratio [aRR]=1.37, P<0.01)
• 102.77 for NOAC alone vs 241.92 for fluconazole (difference=138.46, aRR=2.35, P<0.01)
• 65.66 for NOAC alone vs 103.14 for rifampin (difference=36.90, aRR=1.57, P<0.01)
• 56.07 for NOAC alone vs 108.52 for phenytoin (difference=52.31, aRR=1.94, P<0.01).

The incidence rate for major bleeding was significantly lower with concurrent use of atorvastatin, digoxin, and erythromycin or clarithromycin. The adjusted incidence rates per 1000 person-years were:

• 48.96 for NOAC alone vs 34.57 for atorvastatin (difference=-14.38, aRR=0.71, P<0.01)
• 50.14 for NOAC alone vs 45.69 for digoxin (difference=-4.46, aRR=0.91, P<0.01)
• 99.28 for NOAC alone vs 59.38 for erythromycin/clarithromycin (difference=-39.78, aRR=0.60, P<0.01).

The incidence rates of major bleeding were not significantly different for NOAC use alone and concurrent use of NOACs with verapamil, diltiazem, cyclosporine, dronedarone, and ketoconazole, itraconazole, voriconazole, or posaconazole.

The researchers noted that this study has some limitations, including that bleeding risk and anticoagulant treatment are different in Asian and Western populations. Therefore, the external generalizability of these results, particularly to a Western population, may be limited.

Still, the team said physicians prescribing NOACs should consider the potential risks associated with concomitant use of other drugs.

Rivaroxaban

Concurrent use of non-vitamin K oral anticoagulants (NOACs) and drugs that share metabolic pathways with NOACs may affect the risk of major bleeding in patients with nonvalvular atrial fibrillation (NVAF), according to a study published in JAMA.

Researchers studied more than 91,000 Taiwanese patients with NVAF who were taking dabigatran, rivaroxaban, or apixaban.

Concurrent use of these NOACs with amiodarone, fluconazole, rifampin, or phenytoin was associated with a significant increase in major bleeding, when compared to use of NOACs alone.

On the other hand, major bleeding was significantly decreased for patients concurrently receiving NOACs and atorvastatin, digoxin, or erythromycin/clarithromycin.

Chang-Fu Kuo, MD, PhD, of Chang Gung Memorial Hospital in Taoyuan, Taiwan, and colleagues conducted this study.

The team used data from the Taiwan National Health Insurance database to study 91,330 patients with NVAF who received at least 1 NOAC prescription of dabigatran (n=45,347), rivaroxaban (n=54,006), or apixaban (n=12,886). The patients’ mean age was 74.7, and 55.8% were male.

The researchers estimated the bleeding risk associated with or without the concurrent use of commonly prescribed medications that share metabolic pathways with NOACs—atorvastatin, digoxin, verapamil, diltiazem, amiodarone, cyclosporine, rifampin, phenytoin, dronedarone, erythromycin/clarithromycin, fluconazole, and other azoles (ketoconazole, itraconazole, voriconazole, or posaconazole).

There were 4770 major bleeding events in the patient population.

The data showed that concurrent use of amiodarone, fluconazole, rifampin, and phenytoin with NOACs significantly increased the incidence rates of major bleeding. The adjusted incidence rates per 1000 person-years were:

• 38.09 for NOAC use alone vs 52.04 for amiodarone (difference=13.94, adjusted rate ratio [aRR]=1.37, P<0.01)
• 102.77 for NOAC alone vs 241.92 for fluconazole (difference=138.46, aRR=2.35, P<0.01)
• 65.66 for NOAC alone vs 103.14 for rifampin (difference=36.90, aRR=1.57, P<0.01)
• 56.07 for NOAC alone vs 108.52 for phenytoin (difference=52.31, aRR=1.94, P<0.01).

The incidence rate for major bleeding was significantly lower with concurrent use of atorvastatin, digoxin, and erythromycin or clarithromycin. The adjusted incidence rates per 1000 person-years were:

• 48.96 for NOAC alone vs 34.57 for atorvastatin (difference=-14.38, aRR=0.71, P<0.01)
• 50.14 for NOAC alone vs 45.69 for digoxin (difference=-4.46, aRR=0.91, P<0.01)
• 99.28 for NOAC alone vs 59.38 for erythromycin/clarithromycin (difference=-39.78, aRR=0.60, P<0.01).

The incidence rates of major bleeding were not significantly different for NOAC use alone and concurrent use of NOACs with verapamil, diltiazem, cyclosporine, dronedarone, and ketoconazole, itraconazole, voriconazole, or posaconazole.

The researchers noted that this study has some limitations, including that bleeding risk and anticoagulant treatment are different in Asian and Western populations. Therefore, the external generalizability of these results, particularly to a Western population, may be limited.

Still, the team said physicians prescribing NOACs should consider the potential risks associated with concomitant use of other drugs.

Rivaroxaban

Concurrent use of non-vitamin K oral anticoagulants (NOACs) and drugs that share metabolic pathways with NOACs may affect the risk of major bleeding in patients with nonvalvular atrial fibrillation (NVAF), according to a study published in JAMA.

Researchers studied more than 91,000 Taiwanese patients with NVAF who were taking dabigatran, rivaroxaban, or apixaban.

Concurrent use of these NOACs with amiodarone, fluconazole, rifampin, or phenytoin was associated with a significant increase in major bleeding, when compared to use of NOACs alone.

On the other hand, major bleeding was significantly decreased for patients concurrently receiving NOACs and atorvastatin, digoxin, or erythromycin/clarithromycin.

Chang-Fu Kuo, MD, PhD, of Chang Gung Memorial Hospital in Taoyuan, Taiwan, and colleagues conducted this study.

The team used data from the Taiwan National Health Insurance database to study 91,330 patients with NVAF who received at least 1 NOAC prescription of dabigatran (n=45,347), rivaroxaban (n=54,006), or apixaban (n=12,886). The patients’ mean age was 74.7, and 55.8% were male.

The researchers estimated the bleeding risk associated with or without the concurrent use of commonly prescribed medications that share metabolic pathways with NOACs—atorvastatin, digoxin, verapamil, diltiazem, amiodarone, cyclosporine, rifampin, phenytoin, dronedarone, erythromycin/clarithromycin, fluconazole, and other azoles (ketoconazole, itraconazole, voriconazole, or posaconazole).

There were 4770 major bleeding events in the patient population.

The data showed that concurrent use of amiodarone, fluconazole, rifampin, and phenytoin with NOACs significantly increased the incidence rates of major bleeding. The adjusted incidence rates per 1000 person-years were:

• 38.09 for NOAC use alone vs 52.04 for amiodarone (difference=13.94, adjusted rate ratio [aRR]=1.37, P<0.01)
• 102.77 for NOAC alone vs 241.92 for fluconazole (difference=138.46, aRR=2.35, P<0.01)
• 65.66 for NOAC alone vs 103.14 for rifampin (difference=36.90, aRR=1.57, P<0.01)
• 56.07 for NOAC alone vs 108.52 for phenytoin (difference=52.31, aRR=1.94, P<0.01).

The incidence rate for major bleeding was significantly lower with concurrent use of atorvastatin, digoxin, and erythromycin or clarithromycin. The adjusted incidence rates per 1000 person-years were:

• 48.96 for NOAC alone vs 34.57 for atorvastatin (difference=-14.38, aRR=0.71, P<0.01)
• 50.14 for NOAC alone vs 45.69 for digoxin (difference=-4.46, aRR=0.91, P<0.01)
• 99.28 for NOAC alone vs 59.38 for erythromycin/clarithromycin (difference=-39.78, aRR=0.60, P<0.01).

The incidence rates of major bleeding were not significantly different for NOAC use alone and concurrent use of NOACs with verapamil, diltiazem, cyclosporine, dronedarone, and ketoconazole, itraconazole, voriconazole, or posaconazole.

The researchers noted that this study has some limitations, including that bleeding risk and anticoagulant treatment are different in Asian and Western populations. Therefore, the external generalizability of these results, particularly to a Western population, may be limited.

Still, the team said physicians prescribing NOACs should consider the potential risks associated with concomitant use of other drugs.