In well-designed studies, dabigatran, rivaroxaban, and apixaban have all been shown to be noninferior to warfarin in the initial treatment of acute DVT and pulmonary embolism (PE).14-17 All 3 agents were also shown to have lower rates of major bleeding than warfarin. Rivaroxaban and apixaban were also superior to warfarin with regard to bleeding events, and dabigatran was noninferior to warfarin for this outcome.14-17
NOACs help prevent recurrence
All 3 NOACs have been studied for long-term prevention of recurrent VTE after 3 to 18 months of anticoagulation, as well. Dabigatran was found in the RE-MEDY trial to be noninferior to warfarin for the risk of recurrent VTE, and to have lower rates of bleeding.18 In separate trials, all 3 agents were superior to placebo in preventing recurrent VTE. Rates of long-term major bleeding were significantly higher than placebo with rivaroxaban and dabigatran, but not with apixaban.15,18,19
Rivaroxaban is the only NOAC to be FDA approved for the treatment of acute DVT and PE, and the ACCP’s 2012 guidelines list it as a viable alternative to parenteral anticoagulation when initiating treatment for acute VTE.6,13 When treating VTE long term, the guidelines continue to recommend warfarin or LMWH rather than dabigatran or rivaroxaban.13 Recommendations may change in coming years, as physicians gain more experience with NOACs and more clinical trials are published.16-19
Starting or converting to NOAC therapy
In patients who have not been on anticoagulant therapy, any NOAC can be initiated immediately, with no need for parenteral, or “bridge” therapy. This is because of the rapid onset of action of the NOACs.12
To transition a patient from warfarin to a NOAC, it is necessary to discontinue warfarin therapy completely and closely monitor INR, then initiate NOAC therapy when INR≤2. No parenteral anticoagulation is necessary (TABLE 2).5-7
If it is necessary to transition a patient from a NOAC to warfarin, the protocol depends on the agent. Because dabigatran has no significant impact on prolongation of prothrombin time (PT), it can be overlapped with warfarin. Rivaroxaban and apixaban have a significant impact on PT prolongation, however, and overlapping either agent with warfarin is not recommended.4 Keep in mind that the recommended dosages for the NOACs are not standardized, and can differ drastically depending on the indication for use as well as on patient-specific factors, including renal function, body weight, and age.
Laboratory monitoring is not required
While warfarin has a great deal of interpatient variability and requires frequent lab monitoring, an oft-cited advantage of the NOACs is that they do not require regular monitoring. However, that also has a downside (TABLE 3).1,3-10,12,14-17,20-22 Monitoring INR in patients on warfarin allows physicians to assess patient compliance. And, if a patient on warfarin requires an invasive procedure, coagulation status and bleeding risk can easily be determined. That is not the case with the NOACs.
While some routine laboratory tests may be elevated in a patient taking a NOAC, the degree of elevation does not correlate well with anticoagulant concentration. And, because each NOAC has a different mechanism of action, different measures will be elevated in a patient taking dabigatran vs apixaban or rivaroxaban.4
Activated partial thromboplastin time (aPTT) is the most readily available lab test to assess the presence or absence of dabigatran.4 A normal aPTT indicates that there is little to no dabigatran present.4 But, while an elevated aPTT suggests the presence of dabigatran, it provides little information about how much.4
PT is a useful test to assess coagulation status in patients on either rivaroxaban or apixaban. A normal PT suggests that minimal amounts (or none) of the NOAC are present in the plasma.4 (A direct thrombin inhibitor assay, calibrated to more accurately assess dabigatran concentration, is being developed for clinical use, but is currently available only for research purposes in the United States; a chromogenic antifactor Xa test specific to apixaban and rivaroxaban is also being developed, but is not yet commercially available.4)
What to do when NOAC reversal is required
Patients often need to stop taking an oral anticoagulation in the days leading up to a planned invasive procedure. In an individual with normal renal function who will undergo a procedure with a standard bleeding risk, a NOAC would generally need to be withheld for one to 2 days prior to surgery, given the relatively short half-life. If a patient has acute renal failure or CKD, however, dabigatran may need to be withheld for a prolonged period (3-6 days) in order to safely proceed to surgery.4,23 NOACs may also need to be withheld for 2 to 6 days prior to any surgery with a high risk for bleeding.4