New anticoagulants: a vision of the future

Over the past two decades we have witnessed increased utilisation of anticoagulants for the treatment and prevention of thrombosis in a wide variety of patients. The two mainstay drugs that we have and continue to rely on are heparin (and its derivatives) and warfarin. These drugs have been around for over half a century and we continue to evolve our understanding of their mechanism of action and the best way to use them. There is little doubt that both heparin and warfarin have served us well but it is also fair to acknowledge that their use has come with significant morbidity and mortality. This is primarily related to the poor pharmacokinetics (PK) and pharma-codynamics (PD) of the drugs. Unpredictable absorption, food interactions and drug-drug interactions are all factors that have necessitated frequent testing for the monitoring of the anticoagulant activity. Despite frequent and best monitoring, patients are in the desired anticoagulation range 60% of the time. The rest of the time they are either over or under-anticoagulated and hence at risk of bleeding or recurrent events. The improved understanding of the biochemistry ofthe coagulation system over the past two decades has allowed the design of several new drugs with enhanced PK and PD. These drugs target the two key coagulation enzymes, thrombin and factor X a . The clinical development programsof these drugs are atan advanced stage and several have been approved for use in select application in Australasia and other countries. The improved PK and PD of these drugs allow their use at a fixed dose and without the need for monitoring. The oral bioavailability of these drugs has also considerably simplified our approach to the prevention and treatment of thrombosis. We are about to enter a new era. Are our eyes wide open, or are we going to discover that heparin and warfarin were not that bad really. These are exciting times but I think we need to tread carefully. In my presentation I will review the limitations of current anticoagulants and introduce the new drugs highlighting their advantages and potential limitations.