For the past several decades, warfarin has been the go-to anticoagulant for doctors, but new treatments have recently emerged in the form of direct oral anticoagulants (DOACs). DOACs are considered more effective and safer than warfarin, especially in relation to serious bleeding episodes. These anticoagulants include apixaban, betrixaban, dabigatran, edoxaban, and rivaroxaban.

NATF is dedicated to offering readers a closer look at each DOAC in order to empower patients to make informed healthcare decisions. In this issue of The Beat, NATF takes a closer look at betrixaban:

What is betrixaban? What makes it unique?

Betrixaban, also known as Bevyxxa, is the newest DOAC on the market. It is similar to the other DOACs, but it has a unique purpose: it’s specifically approved to protect medically ill hospitalized patients from developing a blood clot. Patients on betrixaban start with an initial single oral dose of 160 mg and follow that up with a once daily dose of 80 mg for 35 to 42 days. This helps to protect them while they are in the hospital and during the initial period after they’ve been discharged.

Did you know that these hospitalized patients are at a very high risk for developing a blood clot in their lungs (pulmonary embolism or PE) or in their legs (deep vein thrombosis or DVT)? According to the Surgeon General, hospital-acquired PE is the most common and most preventable cause of PE.
Betrixaban was approved for treatment on June 23, 2017, after being fast-tracked by the FDA. This fast-tracked designation was the result of how high the need was to protect these vulnerable patients.

“The fast track designation was applied for the high unmet need,” explained Dr. C. Michael Gibson, an investigator for the APEX trial. “Despite all of the currently available agents, there are still high rates of VTE (venous thromboembolism) development in medically ill patients.”

The APEX trial was the key trial that proved betrixaban could help these patients. The trial was a randomized, double-blind, multinational clinical trial that compared extended duration betrixaban to enoxaparin, the standard treatment for these patients. In the trial, 7,513 patients were randomized to receive betrixaban for 35 to 42 days, with a placebo injection for 6 to 14 days, or an injection of enoxaparin for 6 to 14 days, with a placebo pill for 35 to 42 days. In the end, the trial showed fewer adverse events in patients on betrixaban than those on enoxaparin.

In addition to serving a unique population, betrixaban has several other properties that set it apart from the rest of the DOACs.

“First, it has a longer half-life of nearly one day, where the other agents are half that or less,” explained Dr. Gibson. “This means the drug can truly be given once a day. The other distinguishing property is the very, very low renal clearance of betrixaban. It’s not cleared by the kidney, which makes it particularly attractive for elderly patients who have impaired renal function.”

How does it work?

Betrixaban works by stopping a system known as the “clotting cascade.” The clotting cascade is the system that causes blood to clot. This comes in handy when you are bleeding, but it causes problems when blood clots form where they shouldn’t, such as the lungs or limbs. Betrixaban interrupts the clotting cascade by binding to a factor Xa molecule, stopping the clotting process from continuing.

“All roads to forming a blood clot lead through factor Xa. It doesn’t matter how you kick the process off, you have to go through factor Xa. This drug blocks that step,” summarized Dr. Gibson.

What are the risks?

As with all of the DOAC medications and blood thinners, patients taking betrixaban are at risk for bleeding. Patients and their physicians need to consider this when deciding if this is a medication they should be on.

“Every patient is different. Physicians will need to weigh the patient’s risk of bleeding versus their potential magnitude of benefit,” explained Dr. Gibson, stressing the importance of reading the drug’s package insert.

“Betrixaban has been studied in 7,000 patients and looked to be quite safe. There was no excess major bleeding with the drug,” explained Dr. Gibson, referencing the APEX trial. “There was some excess risk of minor to moderate bleeds. That’s something patients will have to weigh as they make a decision. Do they want to prevent a blood clot going to their lung, or do they want to have light bleeding? I think patients and physicians will have to work together and engage in shared decision making to make the right choice for the right patient.”

Patients with severe renal impairment or those on P-glycoprotein inhibitors should talk to their doctor about receiving the recommended lower dose of the drug.

It is important to take betrixaban exactly as prescribed. If you have missed a dose of betrixaban, see the drug’s package insert to determine your next steps. If you think that betrixaban may be a good option for you, talk to your doctor about your options. Only your personal healthcare provider c an give you the individualized medical advice you need. This DOAC Deep Dive is for informational purposes only.