Oral Factor Xa Inhibitors
Apixaban
The FXa inhibitors are a new class of prophylactic anticoagulants. Apixaban, one of the more recent oral FXa inhibitors, has a half-life of approximately 12 hours, predictable pharmacokinetics, and is cleared primarily via the GI tract. Given its hepatic metabolism, patients taking apixaban along with cytochrome P3A4 inhibitors (eg, certain antibiotics and antifungals) may be at increased risk of bleeding.26 As evidenced by the ARISTOTLE trial, compared to standard treatment with warfarin, apixaban is an effective alternative therapy for patients with atrial fibrillation.27 Of note, however, the ADOPT trial showed increased rates of bleeding in patients with comorbid conditions taking apixaban compared to standard enoxaparin dosing.28
Rivaroxaban
Rivaroxaban is another oral FXa inhibitor, with similar pharmacokinetics as apixaban and a half-life ranging from 8 hours in young healthy subjects to 12 hours in elderly patients. Since one third of the drug is renally cleared, rivaroxaban should be prescribed with caution in patients who have impaired creatinine clearance. Moreover, as the remaining two thirds undergo hepatic clearance, as with apixaban, its use is contraindicated in patients taking other cytochrome P-inhibiting medications.29
The MAGELLAN trial found rivaroxaban to be an effective means of DVT prophylaxis compared to control subjects who received enoxaparin injections, but there was in increased rate of clinically significant bleeding in the rivaroxaban group—arguably one of the more important outcome measures for the emergency provider.30 The ROCKET-AF trial, however, showed reduced rates of stroke in patients who received rivaroxaban versus warfarin. Both drugs had similar rates of major and minor bleeding, but rivaroxaban showed a decrease in intracranial hemorrhage and fatal bleeding.31
Monitoring and Reversal
As with the DTIs, monitoring the anticoagulant activity of factor Xa inhibitors can be a challenge, though various factor X assays have been proposed.31 Similar difficulties likewise exist in terms of reversal. There is no specific reversal agent for the FXa inhibitors, and current treatment guidelines recommend the use of PCCs, APCCs, or recombinant factor VIIa—though limited data exist on which agent to base clinical practice. In contrast to the DTIs, neither apixaban nor rivaroxaban are dialyzable.32 The relatively short half-life of these products, however, can prove beneficial, with cessation of the medication being the first line therapy in the case of any clinically significant bleeding.33
Conclusion
Parenteral DTIs have been utilized for years in the ED setting. With the increasing use of newer oral DTIs and FXa inhibitors, emergency physicians must also become familiar with the drug profile of these products, including appropriate anticoagulation monitoring and effective methods to treat DTI- and FXa-associated bleeding. Many questions remain unanswered about these drugs, necessitating further research—specifically in areas of practical monitoring of anticoagulation and possible reversal protocols in the bleeding patient.
Dr Byrne is a clinical instructor in the department of emergency medicine, Eastern Virginia Medical School, Norfolk. Dr Byars is an associate professor in the department of emergency medicine, Eastern Virginia Medical School, Norfolk.
Disclosure: The authors report no conflict of interest.