Appeal type: Formulary Exception
Decision: Overturned

Diagnosis: Deep vein thrombosis, Pulmonary Embolism
Treatment: Eliquis
The insurer denied the Eliquis.
The determination is overturned.
 
The patient is a female with a history of deep vein thrombosis, pulmonary embolism, hypertension, and morbid obesity who was diagnosed with lower extremity deep vein thrombosis and was started on rivaroxaban. She presented with chest pain and dyspnea. Her symptoms had started the day prior. She was diagnosed with a pulmonary embolism. An inferior vena cava filter was placed. Testing showed evidence of Lupus anticoagulant. The patient was then switched from rivaroxaban to warfarin with enoxaparin bridging. She was unable to tolerate the frequent phlebotomies needed to monitor her international normalized ratio (INR) while on warfarin. She had an acute pulmonary embolism three days after starting treatment with rivaroxaban for deep vein thrombosis. It is unclear whether this represented a treatment failure of rivaroxaban with propagation of the lower extremity clot and subsequent embolism or if the pulmonary embolism was simply a result of a clot that had not yet fully resolved. However, the data regarding the efficacy of direct oral anticoagulants is limited and it is quite possible that rivaroxaban was ineffective. She has now been treated with apixaban (Eliquis) for over a year. At issue is whether the formulary drug will be or has been ineffective, would not be as effective as the non-formulary drug, or would have adverse effects.


This patient requires long-term anticoagulation for a history of deep vein thrombosis (DVT) and pulmonary embolism (PE). The formulary options are warfarin and rivaroxaban (Xarelto). She has previously been intolerant to warfarin. The patient was diagnosed with lower extremity deep vein thrombosis and was started on rivaroxaban. She presented with chest pain and dyspnea. Her symptoms had started the day prior. She was diagnosed with a pulmonary embolism. She has been taking apixaban for over a year.
Direct oral anticoagulants (DOACs), including apixaban, rivaroxaban, dabigatran and edoxaban, are Food and Drug Administration (FDA) approved for the prevention of recurrent deep vein thrombosis (DVT) and pulmonary embolism (PE) and have several advantages over warfarin, including a rapid onset of action with predictable pharmacokinetics and pharmacodynamics, fixed dosing, significantly fewer drug and dietary interactions, and no need for routine laboratory monitoring. Current guidelines endorse the use of one of the four direct oral anticoagulants (DOACs) listed above for long-term treatment of patients with a history of DVT and/or PE.
This issue in question in this particular case is whether rivaroxaban would be less effective or more likely to cause adverse events than apixaban. While a retrospective study suggested that apixaban was more effective in this situation, and associated with fewer major bleeding events, these results have yet to be confirmed by a randomized controlled trial. Per the American Society of Hematology 2020 guidelines for management of venous thromboembolism. "For patients with DVT and/or PE, the American Society of Hematology (ASH) guideline panel does not suggest 1 DOAC over another (conditional recommendation based on very low certainty in the evidence of comparative effects)." Thus, there are no high-quality data suggesting that apixaban would be more effective or safer than rivaroxaban in this particular case. However, this patient has previously been prescribed warfarin and rivaroxaban. She developed a DVT while on rivaroxaban and was unable to tolerate the frequent phlebotomies needed to monitor her INR ratio.
Given that this patient has been stable on apixaban for more than a year with no recurrent thromboembolism, it is this reviewer's opinion that the safest approach is to continue treatment with apixaban.