New oral anticoagulants, NOACS (DOACs), are used widely for therapy of venous thromboembolism and secondary thrombosis prevention, of course. Medications such as dabigatran, apixaban, rivaroxaban, and edoxaban have been used to prevent complications from blood clot formation. What are the nuances of the new oral anticoagulant use? How to compare them to the older anticoagulant medications? And should new oral coagulants now completely supplant warfarin or Coumadin?

The answer to your last question is quasi-solved, nearly solved. Why? Because of the convenience of direct oral anticoagulants, more than their efficacy. Because the pivotal studies established the efficacy of direct oral anticoagulants, and then, of course, use in the real world. The effectiveness of these drugs (DOACs) is usually equivalent when they are studied. It is a known equivalence and non-superiority [of older anticoagulants]. However, there are two main facts about direct oral anticoagulants. The first one is adherence to treatment because direct oral anticoagulants can be given orally, without monitoring, is an advantage. That is a big advantage. There are other advantages of direct oral anticoagulants.

The fact is that their anticoagulant action is evident soon after the administration of direct oral anticoagulants. This gives the advantage that you can start early treatment in the presence of acute thrombosis. But at the same time, it is advantageous when you need to stop the DOC drug because the anticoagulant effect goes off very quickly. The anticoagulant effect of DOACs diminishes much more quickly than that of the drugs with which we need to compare direct oral anticoagulants. These are the vitamin K antagonists (warfarin, coumadin). And there is another advantage of direct oral anticoagulants. This advantage is shown very clearly. It is a lower incidence of intracerebral bleeding. This is, of course, is the most serious complication of any anticoagulant therapy, particularly by vitamin K antagonists. So these are the reasons for direct oral anticoagulants advantage: better convenience, better practicality, and no need of going to the hospital for laboratory monitoring. There is less of the principal side effect and the most dangerous side effect of anticoagulant therapy, cerebral bleeding.

There are also a few disadvantages of direct oral anticoagulants because I think there's mounting evidence that direct oral anticoagulants cause more gastrointestinal bleeding than vitamin K antagonists. But on the whole, the advantages of DOACs are regarding terrible bleeding. Of course, all anticoagulants cause bleeding in special circumstances. But I think, in general, it is easier to handle gastrointestinal bleeding than cerebral bleeding. Overall, it is less frequent as a complication of anticoagulant therapy by direct oral anticoagulants. So I think that's why DOACs (NOACs) are advantageous. I think they are also very advantageous for this fact. The action of direct oral anticoagulants can be reversed easier than the reversal of vitamin K antagonists (coumadin, warfarin). Vitamin K antagonists have a longer half-life. Direct oral anticoagulants have a shorter half-life of a few hours. So, in most instances, when a patient is bleeding, you can simply stop the DOC drug, and the anticoagulant effect will be abetted very soon. Whereas with a vitamin K antagonist, it will take hours, if not days. And so, you need an antidote or a reversal agent. It is the administration of the vitamin K-dependent coagulation factors particularly. In spite of the fact that bleeding might happen, in most instances, the bleeding is not dramatic; it is not very severe. So you do not need reversal agents. They have also developed the antidote for all of these direct oral anticoagulants. It is an Idarucizumab, a reversal agent of thrombin inhibitors. Andexanet reverses direct oral antocoagulants, like apixaban, edoxaban, rivaroxaban. Andexanet is used to reverse all the anti-factor Ten A agents (apixaban, edoxaban, rivaroxaban). It also this product called Ciraparantag, which I don't think is licensed yet. Thename of medication is Ciraparantag. It is useful for reversing all three direct anticoagulants (apixaban, edoxaban, rivaroxaban). But I don't want to emphasize that particularly. In general, these are the antidotes that are useful for a patient after a car accident who is actively bleeding from a wound. You are lucky to have the antidote. But the majority of instances of bleeding, including maybe intracerebral bleeding, which is less frequent, you don't need reversal agents. Because you simply stop the drug. And the advantage of direct oral anticoagulants (DOACs) is that after a few hours, the drugs will be clear from blood. So direct oral anticoagulants (DOACs) will fully replace the older oral anticoagulants. It is certainly true in our center. Direct oral anticoagulants (DOACs) have nearly replaced [warfarin and coumadin], particularly for elderly patients and in other patient populations that have a higher risk of bleeding, particularly of gastrointestinal bleeding.

I think that, ultimately, direct oral anticoagulants (DOACs) will fully replace the vitamin K antagonists. Because, of course, if I look at the list of the most expensive drugs in Italy, among the 20 most expensive medications, the first is an antihemophilic product, but there is also a direct oral anticoagulant (DOACs). But now, DOACs are given without limitation. Direct oral anticoagulants (DOACs) can also be prescribed by General Practitioners. Probably the regulatory agency is monitoring prescriptions of DOACs, so there is no excessive consumption. So I think the use of vitamin K antagonists (warfarin, coumadin) will continue because they are cheaper. They can be used in countries that are not high-income countries. But altogether, the only situation in which they are still needed is in the treatment of patients that have mechanical heart valves. It is due to heart valve disease. This is a big problem, but not so much in high-income countries. It is more important in low-income countries where cardiac surgeons have the problem of monitoring these mechanical heart valves. And, of course, it's very difficult in Sudan or Africa to go to the medical centers to do the INR. So I think there is room for vitamin K antagonists. But in most high-income countries, they will be replaced by direct oral anticoagulants (DOACs). And you mentioned atrial fibrillation. Certainly, direct oral anticoagulants (DOACs) can be used for atrial fibrillation. But DOACs can also be used for deep vein thrombosis, for secondary prevention of vein thrombosis, and prevention of stroke in atrial fibrillation.