The therapeutic potential of novel anticoagulants

For several decades, conventional anticoagulant therapy has been based on indirect inhibition of coagulation factors with heparin and warfarin (coumadin). Although used widely and effectively, heparin and warfarin display liabilities which have prompted the development of new anticoagulants over the last two decades. The first to be developed was a series of low molecular weight heparins (LMWHs). Their favourable pharmacokinetic profiles and risk/benefit ratios led to widespread use in Europe and more recently, approval for their use in the USA. Paralleling the development of LMWHs, but lagging behind in terms of clinical development, has been the pursuit of a different strategy focused on direct rather than indirect inhibition of enzymes in the coagulation cascade. In contrast to heparin, LMWHs, or other glycosaminoglycans, direct inhibitors, exert their effects independent of either antithrombin III (ATIII) or heparin co-factor II (HCII) and more effectively inhibit clot-bound thrombin or FXa. Highly po...