Andexanet as an Antidote for Oral Anti-Factor Xa Anticoagulants—Commentary

People who have certain disorders, such as a blood clot in their leg or lungs, or atrial fibrillation usually need to take drugs that slow down the ability of the blood to clot. These drugs are called anticoagulants or blood thinners. Because these drugs interfere with clotting, people who take anticoagulants are at risk of bleeding. The bleeding can be life-threatening. A common anticoagulant that has been used for many years is warfarin (Coumadin). If bleeding occurs in people taking warfarin, the bleeding can be stopped by giving the person vitamin K and fresh-frozen plasma.

However, people who take warfarin need to have frequent blood tests so that doctors can see whether to change the dose of warfarin. People taking warfarin also have to eliminate certain foods from their diets and be cautious about taking certain other drugs because certain foods and drugs change the effectiveness of warfarin.

 Newer oral anticoagulants, such as apixaban (Eliquis) and rivarixaban (Xarelto)  have an advantage over warfarin in that people do not need blood tests and do not need to change their diet. These drugs, called factor Xa inhibitors, block the action of factor Xa, which is one of the body’s substances that helps stop bleeding. Like warfarin, these newer anticoagulants can cause bleeding. However, unlike warfarin, there was no drug available to reverse the action of these anticoagulants if severe bleeding occurred.

A recent news article reported on the development of a cleverly designed antidote for factor Xa inhibitors. This drug, andexanet, may fill this important therapeutic gap.

The study found that when andexanet was given to healthy people who had taken an anticoagulant, it restored the function of factor Xa and caused no adverse effects.

Blood specialists such as myself are optimistic that andexanet is very likely to be able to control severe bleeding caused by factor Xa inhibitors. However, we don’t know for sure because doctors have not yet finished tests of andexanet in people who actually have bleeding. Until these studies are done and the drug is shown to improve the outcome in people who are bleeding, we must take a wait-and-see attitude. But if the new tests are successful, many doctors will feel more comfortable prescribing the newer, easier to use anticoagulants because they would have an antidote to use if bleeding occurred.

It is worth noting that another newer anticoagulant, dabigatran (Pradaxa), has not had an antidote until this October, when idarucizumab (Praxibind) became available.

Effective, safe antidotes to the newer oral anticoagulants will be a helpful and timely addition to the care of people who require long term anticoagulant therapy.