Survival of Heparins, Oral Anticoagulants, and Aspirin after the Year 2010

The conventional management of thrombotic and cardiovascular disorders is based on the use of heparin, oral anticoagulants, and aspirin. Despite remarkable progress in life sciences, these drugs still remain a challenge and a mystery to us, and their use is far from optimized. The development of low-molecular-weight heparins and the synthesis of heparinomimetics, such as the chemically synthesized pentasaccharide, represent a reﬁned use of heparin. Additional drugs from this knowledge will continue to develop; however, none of these drugs will ever match the polypharmacology of heparin. Aspirin still remains the leading drug in the management of thrombotic and cardiovascular disorders. The newer antiplatelet drugs such as adenosine diphosphate receptor inhibitors, glycoprotein IIb/IIIa inhibitors, and other speciﬁc inhibitors have limited effects and have been tested in patients who have already been treated with aspirin. Warfarin provides a convenient and affordable approach in the long-term outpatient management of thrombotic disorders. The optimized use of these drugs still remains as the approach of choice to manage thrombotic disorders. The new anticoagulant targets, including speciﬁc sites in the hemostatic network such as tissue factor, individual clotting factors (IIa, VIIa, IXa, Xa, XIIa, and XIIIa), recombinant forms of serpins (antithrombin, heparin cofactor II, and tissue factor pathway inhibitors), recombinant activated protein C, thrombomodulin, and site-speciﬁc serine protease added a new dimension in the management of thrombotic disorders. The favorable clinical outcomes with aspirin and clopidogrel have validated cyclooxygenase (COX)-1 and P2Y 12 receptors as targets for new drug development. Prasugrel, a novel thienopyridine, cangrelor, and AZD 6140 represent newer P2Y 12 antagonists. Cangrelor and AZD 6140 are direct inhibitors, whereas prasugrel requires metabolic activation. Though clinically effective, recent results have prompted a closure of a large clinical trial with prasugrel due to bleeding. The newer anticoagulant and antiplatelet drugs are attractive for several reasons; however, none of these are expected to replace the conventional drugs in polytherapeutic approaches. Heparins, warfarin, and aspirin will continue to play a major role in the management of thrombotic and cardiovascular disorders beyond 2010. a complex multicomponent pathologic process involving both cellular and humoral factors. Endothelial damage, cellular activation, release of mediators (including inﬂammatory components), and modulators of vascular tone all contribute to the overall pathogenic mechanisms. The complete understanding of the thrombogenic process is not known, but it is known that it is not fully dependent on the generation of thrombin and related enzymes. TFPI, tissue factor pathway inhibitor; TAFI, thrombin-activatable ﬁbrinolysis inhibitor; PAI-1, plasminogen activator inhibitor-1; TF, tissue factor; NO, nitric oxide; TXB 2 , thromboxane B 2 ; LTs, leukotriene; FPA, ﬁbrinopeptide A; PAI-1, plasminogen activator inhibitor-1; PF4, platelet factor 4; C5a, complement C5a; s-TM, soluble thrombomodulin; F1.2, prothrombin fragment F1.2, PAP, plasminogen antiplasmin complex; TAT, thrombin antithrombin complex.