Current indications for the new oral anticoagulants
The indications for the new oral anticoagulants in the United States and the licensed doses are summarized in Table 4. In the United States, Europe, Canada and many other countries, dabigatran and rivaroxaban are licensed as alternatives to warfarin for prevention of stroke or systemic embolism in patients with atrial fibrillation. It is likely that apixaban will soon be licensed for this indication and it is possible that apixaban may also be approved as an alternative to aspirin in atrial fibrillation patients who are unable or unwilling to take warfarin. However, there are country-specific differences in the licensed doses of dabigatran and the in the use of dabigatran and rivaroxaban in patients with a creatinine clearance below 30 mL/min. In the United States, the 150 mg twice-daily dose regimen of dabigatran is licensed for all patients with a creatinine clearance more than 30 mL/min, whereas a dose of 75 mg twice daily is approved for patients with a creatinine clearance of 15 to 30 mL/min. The latter dose regimen was selected based on pharmacokinetic data indicating that it yields drug exposures in patients with impaired renal function similar to those produced by the 150 mg twice-daily regimen in patients with normal renal function. In contrast, in all other countries, dabigatran is contraindicated in those with a creatinine clearance below 30 mL/min. The 110 mg twice-daily dabigatran regimen is approved in all countries except the United States and is the dose recommended for those 75 to 80 years of age or older, and for patients at risk of gastrointestinal bleeding. For rivaroxaban, the 20 mg once-daily dose is licensed in the United States, Europe and Canada for patients
with a creatinine clearance of 50 mL/min or higher, whereas a dose of 15 mg once-daily is approved in the United States for those with a creatinine clearance of 15 to 49 mL/min. In contrast, in all other countries, the 15 mg once-daily dose of rivaroxaban is restricted to patients with a creatinine clearance of 30 to 49 mL/min and the drug is not recommended in those with a creatinine clearance below 30 mL/min.
In the United States, Europe and Canada rivaroxaban is licensed for thromboprophylaxis after elective hip or knee replacement surgery. Although dabigatran and apixaban also are licensed for this indication in Europe and Canada, this is not the case in the United States. Likewise, rivaroxaban is licensed in Europe and Canada for treatment of deep vein thrombosis, but not yet in the United States. Finally, based on the results of the ATLAS-2 trial,13 rivaroxaban is likely to be licensed as an adjunct to antiplatelet therapy to prevent recurrent ischemic events in patients with stabilized acute coronary syndrome.
With the availability of several new oral anticoagulants and the expanding list of licensed indications, how do we choose the right drug for the right patient?