<International Circulation>: Antithrombotic therapies in acute coronary syndromes are always an important issue. New anticoagulants are constantly emerging. What is the current state-of-the-art and what does the future hold in this area?

    Prof. Verheugt: In the management of acute coronary syndromes， there has been huge attention in the last 15 years on improving antiplatelet therapy. Of course， there is aspirin which is the cornerstone of treatment for acute coronary syndromes. Since we know more about platelet physiology and pathophysiology， new drugs have been developed but most of them failed， with only clopidogrel making it to the market. The intravenous glycoprotein IIb/IIIa inhibitors were introduced but I believe have already been replaced by oral drugs. During those years， we almost abandoned the search for anticoagulants because to make a clot in a vessel you need the coagulation proteins and the platelets and the coagulation pathways were forgotten. In the last few years， we have seen a huge improvement in these treatment strategies where you interfere with the coagulation cascade. We had heparin and it is important together with aspirin of course but it is a nasty drug to use. It is unpredictable in its effect and may cause excessive bleeding. Then the low-molecular-weight-heparins arrived and were not much of an improvement but were easy to administer by subcutaneous injection and requiring no monitoring. They were， however， aspecific in their actions. Now we have more specific IV blockers of the coagulation cascade – bivalirudin is a good example. It is still too early to use it in all patients and it is expensive too. More options are required for the IV route. For the oral anticoagulants there has been good progress. We continue to use warfarin， but not very often in acute coronary syndromes worldwide but in the Netherlands it has been quite popular. It is a very effective agent but difficult to use because of monitoring of the INR. We now have direct oral blockers of thrombin which do not need any monitoring， and we have direct blockers of factor Xa， both interfering with the final common pathway of the coagulation cascade. When you combine these with antiplatelet drugs you get increased bleeding but you will also see increased efficacy. In the whole setting of antithrombotic therapy in the acute coronary syndromes， there always needs to be a balance between efficacy and bleeding. Effect and side effect.