Thrombosis, the result of a complex interplay between platelet activation and activation of the coagulation cascade, is a key pathophysiological mechanism in many cardiovascular disorders, including acute coronary syndromes and atrial fibrillation. Atrial fibrillation (AF) is associated with an increased risk of systemic emboli caused by intra-atrial thrombus formation, triggered by mechanical and haemostatic disturbances. In acute coronary syndromes (ACS), plaque rupture exposes von Willebrand factor and collagen, triggering platelet adhesion and activation. The coagulation cascade is also activated by complex formation of tissue factor with activated factor VII. This complex, in turn, leads to activation of factor X and subsequently thrombin formation.
Anticoagulation with warfarin, a vitamin K antagonist, is the mainstay of the prophylactic treatment of stroke and systemic embolic events in most patients with AF.1
An international normalised ratio (INR) of 2 to 3 is the usual target level of anticoagulation in AF. Inhibiting the coagulation cascade has also been extensively studied in ACS. The benefits of short term treatment after ACS with aspirin and heparin are well known. Nevertheless, there is evidence of a clinically relevant prothrombotic reactivation after cessation of heparin treatment,2,3
suggesting that prolonged antithrombin treatment after ACS could be desirable. Indeed, extended administration of high intensity warfarin and moderate intensity warfarin in combination with aspirin also reduces ischaemic complications after ACS.4–6
Until now, vitamin K antagonists, such as warfarin, are the only clinically available oral anticoagulants. Chronic anticoagulation, however, is often cumbersome. Not only does the effect of warfarin differ among patients, it also varies over time in the same individual. Also, various intercurrent illnesses, drugs, and food can influence the level of anticoagulation. Therefore, repeated monitoring of the anticoagulant effect and careful adjustments of warfarin dosage is necessary. In spite of these adjustments oral anticoagulation is associated with an increased risk of bleeding complications. These caveats explain in part why over 40% of patients with AF do not receive anticoagulant treatment, and why physicians are reluctant to give prolonged anticoagulant treatment after ACS.