The anticoagulant dilemma--a prescription for its resolution

Despite the fact that heparin and the coumarins are effective drugs in the prevention of venous thromboembolism and of systemic embolism and have been in use for more than one quarter of this century, there has been no recognized decrease in overall deaths attributable to these agents. Several factors contribute to this paradox: (1) the disparity between the high prevalence of thromboembolic events and the low incidence of associated mortality or disability has rendered the required size of trial populations exceedingly large, cumbersome, and costly; (2) the major use of anticoagulants has occurred after a thromboembolic event rather than as an instrument of primary prophylaxis; (3) the difficulties in regulating drug dosage persist and serious hemorrhage remains in infrequent but real complication of therapy; and (4) the physician is invariably apprised of clinical failure (further thrombosis or hemorrhage) but rarely of success (no thrombosis). Recent advances in our understanding of the mechanism of intravascular coagulation, of the pathophysiology of thromboembolism, and of the molecular basis of anticoagulant action have begun to permit more effective use of the classical drugs and to suggest the potential value of other agents and modalities for the prevention of the thromboembolism in different segments of the vasculature.