Real Costs of Apixaban vs. Warfarin for DVT

This is just a brief post to start a conversation on the cost of treatment of acute deep vein thrombosis (DVT)  with initial low molecular weight heparin plus warfarin vs the new and per-pill expensive apixaban (Eliquis®) recently approved by the FDA for this treatment of acute DVT and pulmonary embolism. Warfarin therapy has been the standard treatment for the potentially life threatening and quite common condition called deep vein thrombosis, which occurs when a blood clot forms in the veins of the legs with the potential to break loose and travel to the lungs.  When the clot lodges in the lung circulation it is called a pulmonary embolus and can cause sudden death in some cases. Warfarin works by interfering with the vitamin K dependent synthesis of clotting factors in the liver, which takes several days to give effective anticoagulation, so use of a faster acting anticoagulant is needed. In  recent years a form of heparin that can be used outside the hospital has made outpatient therapy of some cases of DVT.  Patients are treated with this low molecular weight heparin until the warfarin has time to take effect, and the dose of warfarin needed for an individual is refined.  This means a patient needs to use once or twice daily injections of heparin for about a week.   Apixaban works very quickly because it directly interferes with the clotting cascade, so initial heparin is not needed.

The typical dose of apixaban, 5 mg twice daily is about $8.98 / day ( vs. a typical 5 mg dose of warfarin at $0.13 / day. This sounds like it’s not even close, but the devil is in the details. Patients can start on apixaban  at the time of diagnosis without use of initial heparin therapy, a considerable cost savings.   In addition therapy with warfarin requires frequent monitoring with lab tests and dosage adjustments, each test and dose adjustment adding a lab and provider fee. Let’s look at a comparison of the bare basics for a typical 6 month course of therapy with initial enoaparin (the type of low molecular weight heparin used in the head-to-head study) along with warfarin, vs. treatment from the time of diagnosis with apixaban. We will assume an 80 kg patient needing 80 mg of enoxaparin injected twice daily for 7 days, a daily dose of 5 mg of apixaban and 5 mg of warfarin (same mg dose strictly coincidence, these are typical doses) , 12 anticoagulation clinic visits for patients on warfarin at $75/ visit, and no other costs at all.

Apixaban Warfarin Difference
Drug cost 1639. 19.34 1619.75
Monitoring costs 0 900. -900
Initial enoxaparin Cost 0 343.87 -343.87
Initial cost of 6 monthsOf drug therapy 1639. 1263.21 375.88

For a 6 month course of treatment the much more expensive drug becomes less dramatically more expensive. This assumes the same amount of physician follow up visits, equal costs of any further diagnostic tests, equal costs for complications and treatment failures. These added assumptions may not be true, but the initial published study of apixaban vs. warfarin therapy showed non-inferiority and both failure rates and bleeding complication rates statistically non-significantly favoring apixaban. I have no data on the actual frequency of need for anticoagulation testing, or the actual duration of need for low molecular weight heparin use in real life, but I chose conservative estimates in my opinion.  It is not unusual to have considerable difficulty in achieving initial adequate but not excessive anticoagulation in patients new to warfarin, and studies have shown in the best of circumstances only about a 60% rate of therapeutic INR values in anticoagulation monitoring.  More than 12 visits for testing in the 6 months of therapy would not be exceptional.
The concerns that the new oral anticoagulants do not have a means of rapid reversibility remains, and much aftermarket data is yet to come in, but if the argument against use of apixaban is that the expense of using apixaban for a new onset DVT or PE diagnosis is the reason for choosing warfarin then I want to see a more eloquent and detailed analysis of costs.  I suspect many patients when offered a cost differene for a 6 month course of therapy of less than $400. to avoid the need for 14 injections, 12 b lood tests and visits to an anticoagulation clinic (far from cheap if missing work is needed for any of these visits) because my initial crude calculations don’t support a huge cost difference.

The analysis for treatment of atrial fibrillation to prevent stroke becomes more difficult because of the very uncertain duration of therapy.  The same arguement applies in patients with DVT for whom an indefinate duration of anticoagulation is anticipated.  In addition if the use of apixaban allows outpatient therapy vs. inpatient therapy for even one day then the cost of warfarin with admission skyrockets.

Any thoughts from readers on this analysis? Leave a comment.

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