Practical questions on therapy with new antithrombotic agents

Czech version

Authors: Jan Vojáček
Authors‘ workplace: I. interní kardioangiologická klinika LF UK a FN Hradec Králové, přednosta prof. MUDr. Pavel Červinka, Ph. D.
Published in: Vnitř Lék 2014; 60(4): 389-395
Category: 60th Birthday - prof. MUDr. Petr Widimský, DrSc., FESC, FACC

Overview

Recently, new peroral antithrombotic agents have proved better prevention of thrombotic complications in many clinical events such as acute coronary syndrome, tromboembolic disease or atrial fibrillation. New peroral anticoagulants (NPA) were introduced – dabigatran, rivaroxaban and apixaban and new antiplatelet agents – ticagrelol and prasugrel. Outcomes of pilot studies: RE-LY, ROCKET AF, ARISTOTLE, PLATO a TIMI 38 TRITON and subsequent clinical experiences supported their usage. NPA have proved non-inferiority in incidence of stroke or systemic embolism. Moreover, apixaban and dabigatran with administration of 150 mg twice a day have proved superiority. In addition, all 3 molecules have been non-inferior in incidence of severe bleeding. Apixaban and dabigatran – 110 mg twice a day have been proved as superior. Therefore, the guidelines favour NPA before warfarin in most patients. Previous antiplatelet agent – clopidogrel is ineffective due to genetic polymorphism in P450 (polymorphism of CYP2C19 and CYP3A4 allele – *1 isoforms in function, *2 and *3 non-functioning alleles) and due to failure of metabolic conversion to active molecule. This resistance depends on population and is present in 20–35% patients. New antiplatelet medications have faster and more homogenous onset in comparison with clopidogrel. Their metabolism is different and resistance is not so frequent. Prasugrel is contraindicated in patients after stroke or TIA, in elderly patients (more than 75 years) and in patients with weight less than 60 kg. Prasugrel has data of benefit especially in patients with STEMI or diabetes. Ticagrelor reduces mortality in patients with acute coronary syndrome concurrently without clinically significant bleeding comparing ticagrelor to clopidogrel administration. On the other hand, higher incidence of significant bleeding has been revealed unrelated to aortocoronary bypass with ticagrelor therapy, including higher incidence of fatal intracranial hemorrhage and reduced incidence of fatal hemorrhage of other types. Ticagrelor significantly reduced the primary end-point compared to clopidogrelu in patients with chronic kidney disease and creatinine clearance 30–60 ml/min. In addition, ticagrelor reduces all cause mortality in these patients. New antithrombotic agents have brought improvement not only in reducing the incidence of thrombotic and bleeding complications, but in decision-making algorithm as well. However, search for optimal therapy of thrombosis will clearly require more intensive clinical research.

Key words:
new peroral anticoagulants – prasugrel – ticagrelor

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