Current trends in antithrombotic drug and device development.

Abstract

During the past decade, many significant developments in the clinical management of thrombotic and vascular disorders have occurred. In particular, several newer approaches for the prophylactic and therapeutic management of such disorders as venous thrombosis, acute myocardial infarction, and stroke have been introduced. This has been possible because of the understanding of the molecular mechanisms involved in the thrombogenic process, which plays a key role in the pathophysiology of thrombotic and vascular disorders. With the increased knowledge of the pathophysiology of thrombosis have come advances in drug treatment possibilities. Advances in biotechnology and separation techniques have contributed to the development of many newer antithrombotic, anticoagulant, and thrombolytic drugs. Many new drugs and devices based on newer concepts are currently being tested in various clinical trials. Hirudin, hirulog, GPIIb/IIIa targeting antibodies, and tissue factor pathway inhibitor are some examples. From these current developments, it can be appreciated that antithrombotic drugs represent a wide spectrum of natural, synthetic, semisynthetic, and biotechnology-produced agents with marked differences in chemical composition, physicochemical properties, biochemical actions, and pharmacologic effects. The use of physical means to treat thrombotic disorders and advanced means of drug delivery add to the expanding nature of treatment. The endogenous actions of the antithrombotic drugs are quite complex. It is no longer valid to assume that an antithrombotic drug must produce an anticoagulant action in blood, as do the classical heparin and oral anticoagulants. Many of these new drugs do not produce any alteration of currently measurable blood-clotting parameters, yet they are effective therapeutic agents because of their interactions with the elements of the blood and the vasculature. Another perspective is that several of these agents require endogenous transformation to become active products. Therefore, it becomes important to rely on the pharmacodynamic actions of these agents rather than on other in vitro characteristics to assess potency or efficacy. Hematologic and vascular modulation play a key role in the mediation of the antithrombotic actions of these drugs, involving red cells, white cells, platelets, endothelial cells, and blood proteins. Thus, an optimal antithrombotic drug approach will include the targeting of all possible sites involved in thrombogenesis. Antithrombotic and anticoagulant drugs will also be useful in the development of such biomedical devices as stents and other vascular support material. Polytherapeutic approaches utilizing combinations of drugs may turn out to be the most effective in the management of thrombotic disorders.