Antidote for xabans

NOAC drugs are undoubtedly a breakthrough in the prevention of ischemic strokes in patients with atrial fibrillation. Why is their appearance so important?

For years, in anticoagulant treatment we could only use vitamin K antagonists, the most frequently used of which is warfarin. However, warfarin treatment is associated with numerous restrictions regarding diet, simultaneous use of other medications, the need to individually adjust the dose, and therefore frequent blood sampling to monitor coagulation. Fortunately, for over 10 years we have had a group of drugs that we initially called new oral anticoagulants (NOACs – novel oral anticoagulants). Now they are no longer new, but the abbreviation remains. New oral anticoagulants act on various stages of the coagulation system. There are three drugs from this group available in Poland: dabigatran (thrombin inhibitor) and two xabans (rivaroxaban and apixaban, which are factor Xa inhibitors). Each of them has been compared with warfarin in large studies.

All of them are at least as effective as warfarin, but safer than it, i.e. causing fewer bleeding complications. Therefore, they are the drugs of choice for stroke prevention. Additionally, they are easy to use because there is no need to monitor the coagulation system, the dosage does not depend on diet, and they are easier to combine with other drugs, although kidney function needs to be monitored from time to time.

In the prevention of stroke in patients with atrial fibrillation, NOAC drugs are not reimbursed in Poland. But although they are not reimbursed, due to their advantages and the fact that they have a class I recommendation, i.e. the strongest, they are widely used. However, we are approaching the moment when reproductive drugs will appear, the so-called generics, the price of which will be much more affordable for patients.

NOAC drugs, due to their mechanism of action, pose a risk of bleeding, which may even be life-threatening. Are there any preparations available in Poland that reverse their effects?

Anyone who takes anticoagulants has a slightly increased risk of bleeding complications. Bleeding can be small, but unfortunately also large, clinically significant and life-threatening. Heavy bleeding does not always mean loss of a large volume of blood. Sometimes the location of the bleeding itself is dangerous, for example in the central nervous system or the eyeball. In such situations, reversing the effects of drugs is very helpful.

The second group of patients requiring inhibition of the action of anticoagulants are people who need immediate surgery.

The action of dabigatran is blocked by a drug called idarucizumab, which has been available for several years. An antidote to xabans has recently been registered. First, the drug was approved by the US Drug Administration, then the European one. This is andexanet alfa, which specifically inhibits the action of these drugs. It is only registered for the indication “uncontrolled or life-threatening bleeding”. There is no indication related to surgery, as is the case with idarucizumab. Despite the lack of registration, it happened that andexanet alfa was administered to a patient taking rivaroxaban or apixaban when an immediate life-saving operation was necessary.

Antidotes for NOAC are not reimbursed in Poland. Both are quite expensive. Andeksanet alfa is becoming available in Poland on a similar basis to idarucizumab – hospitals can take it on commission from the manufacturer, they do not have to pay for it immediately. They pay their bills for the amount they consume.

Andexanet alfa is currently the only recommended method for reversing the effects of rivaroxaban and apixaban, but the class of recommendations in various guidelines varies. The guidelines of the European Society of Cardiology, also valid in Poland, say to consider administering a specific antidote in the event of severe or life-threatening bleeding. In short, this is a very good solution for a relatively narrow group of patients. Intracranial bleeding occurred in 0.3-0.5% of cases in this population. There is slightly more bleeding from the gastrointestinal tract, but in these situations, apart from discontinuing the anticoagulant drug, an attempt is made to control the bleeding using the endoscopic method.

Interviewed by Iwona Kazimierska