Health care providers are questioning how to select the new oral anticoagulants with direct factor Xa inhibitor activity, rivaroxaban (Xarelto), apixaban (Eliquis), and edoxaban (Savaysa) OR direct thrombin inhibitor activity, dabigatran (Pradaxa). There are currently four drugs available in these classes with several references, new or novel oral anticoagulants (NOACs), direct oral anticoagulants (DOACs) and target-specific anticoagulants (TSACs). We will use the term NOAC for this article. Another agent, betrixaban, is expected to be released in the next.
When compared to the vitamin K antagonist, warfarin, each of the NOACs has a unique set of approved indications, dosing, clinical and therapeutic considerations and drug interactions. See the attached Comparison of Oral Anticoagulants for a detailed view of these differences and assistance in selecting the appropriate agent.
In 2014 NEPHO had a 53% increase in expenses for the NOAC class of medications as compared to the previous year. In addition, the average cost per prescription was $262 vs. $80 per month for warfarin including INR testing.
There are several considerations when selecting an agent for the most common indications for chronic oral anticoagulation, atrial fibrillation (AF) and venous thromboembolism (VTE) including deep vein thrombosis (DVT) and pulmonary embolism (PE).
See below for some guidance:
- Generally, if a patient is currently on warfarin and INRs are stable there is no compelling reason to switch to a NOAC
- NOACs are indicated for nonvalvular AF, warfarin is currently the preferred agent for patients with mechanical heart valves
- All NOACs have been proven to be as least as effective as warfarin for current indications; no current data available comparing NOACs to each other
- Advantages vs. warfarin:
- rapid onset/offset of action
- more predictable pharmacologic profiles
- less drug / food interactions, (see Comparison of Oral Anticoagulants) but consider:
- warfarin - drug interactions can be managed with increased monitoring and dose adjustments and are not contraindicated
- NOACs - drug interactions are contraindicated or a precaution; no ability to monitor and dose adjust based on response.
- Disadvantages vs. warfarin:
- cost (~$262 vs $80 per month); (particularly important for Medicare Part D patients as once annual drug costs total $2,960, the donut hole is reached and patient is responsible for 45% - 65% of the cost of drugs and must pay out of pocket until a total of $4,700 drug expenses is reached.)
- out-of-pocket costs based on insurance; copays range from $25 - $75
- currently no antidote (although one in the works for dabigatran/Pradaxa)
- Dabigatran/Pradaxa and apixaban/Eliquis may prevent more strokes than other current NOACs
- Rivaroxaban/Xarelto and edoxaban/Savaysa may benefit patient requiring once a day dosing; others are twice daily; warfarin once a day.
- Check patient weight before starting NOACs: apixaban/Eliquis and edoxaban/Savaysa dose adjusted for weight < 60 kg
- All require renal some dosing adjustment; suggest renal function monitoring with all the new anticoagulants; edoxaban/Savaysa should be avoided if CrCl is OVER 95 mL/min (yes that is OVER)
Bottom line: select an oral anticoagulant based on indication, interactions, renal function, formulary status, and patient preference.
2014 AHA/ACC/HRS Guidelines for Management of Patients with Atrial Fibrillation
Lexicomp Accessed June 2015
Comparison of Oral Anticoagulants Prescriber Letter June 2014