The long path to NOAC^[*]

Summary

The discovery of anticoagulant drugs occurred at a time when the process of blood coagulation only had been roughly described and their mode of action was unknown. Nevertheless, heparin – which was discovered 100 years ago – and warfarin – which was developed in the 1920s – had taken off on a triumphal course which is unique in medical history. The synthesis of anticoagulants with targeted mode of action was only achieved at the end of the last century, e. g. the inhibitor of factor Xa fondaparinux or the recombinant production of the direct thrombin inhibitor hirudin, closely followed by the synthesis of the direct oral inhibitors of factor Xa and thrombin. These compounds had been clinically developed in the early 21st century and meanwhile, they have become available for several indications. Dabigatran is the only thrombin inhibitor and rivaroxaban, apixaban and edoxaban are the three factor Xa inhibitors which entered the market and have started replacing the conventional anticoagulants for treatment of venous thromboembolic complications and for prevention of stroke in patients with atrial fibrillation. They have several characteristics in common such as a reproducible bioavailability, much shorter halflives than vitamin K antagonists, low interaction with other drugs, fixed dosing regimens without the necessity for routine coagulation controls and a better risk-/benefit profile than conventional anticoagulants. However, there are differences between the various compounds with regard to metabolism, renal elimination and the various dosing regimens which definitely need to be considered when prescribed to various patient populations.

Keywords

Heparin - low molecular weight heparins - vitamin K antagonists - oral anticoagulants - NOAC

¹ This paper is essentially based on the lecture given by the author to the 57th Annual Congress of the German Society for Phlebology in Bamberg on the occasion of the presentation of the Max Ratschow medal, which was awarded by the Curatorium Angiologiae Internationalis in recognition of her lifetime’ s work. “ The long path to NOAC ” is thus also a summary of her academic life devoted to this topic and contains a corresponding excerpt of the list of publications in the literature.

• References

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