Individualized antithrombotic therapy
Authors: Steffel J. , Lüscher T. F. 
Published: January 2015

SummaryClot formation in the circulation is a physiological mechanism preventing bleeding at sites of loss of vascular integrity. Clot formation may also occur intravascularly under pathological conditions, e. g. leading to myocardial infarction, stroke, and critical limb ischaemia. Clot formation involves activation of the coagulation cascade and of platelets eventually leading to an occlusive clot. In the venous circulation, clots are rich in erythrocytes and fibrin, while in the arterial circulation platelets predominate. Accordingly, drugs have been developed to interfere with the activation of the coagulation and/or platelets. As several coagulation factors such as factor VII, VIIII, X and thrombin (factor II) are vitamin K-dependent, drugs interfering with the effects of the vitamin (VKAs), i. e. warfarin, marcoumar or sintrom have been used for decades to prevent thromboembolism and embolic stroke. With the advent of selective inhibitors of factor X (apixaban, edoxaban and rivaroxaban) or factor II (dabigratan) the therapeutic spectrum of anti-thrombotic therapy has been expanded. On the other hand, platelet inhibitors such as aspirin and thienopyridines, i.e. clopidogrel, prasugrel, and ticagrelor have extensively been used to treat arterial disease in the coronary, cerebrovascular and peripheral circulation. Individualized antithrombotic therapy considers (1) characteristics of the disease and (2) those of the patient. Such a decision tree first separates “arterial” and “venous” thrombi. For the prevention of arterial thrombi that occur in acute myocardial infarction and certain forms of stroke and critical limb ischemia, platelet inhibitors are indicated. The first line drug is aspirin which interferes with thromboxane A2 (TXA2) formation and partially inhibits platelet activation. In patients receiving a stent or in acute coronary syndromes (ACS), the combination of aspirin with a thienopyri-dine is indicated. On the other hand, patients with venous clots should be treated with anticoagulants interfering with the activation of the coagulation cascade. While the longest experiences exist with vitamin K antagonists, the novel oral anticoagulants (NOACs) are at least as effective, but associated with less intracerebral and life-threatening bleeding. VKAs remain the treatment of choice in patients receiving artificial heart valves or with renal failure (in general a GFR of 30 ml/min/KG or less). In the remaining patients, current evidence suggests that NOACs should be preferred. The NOACs are well documented in patients with thromboembolism and atrial fibrillation. Whether patients with an acute ACS should receive dual antiplatelet drugs plus a low dose NOAC is a matter of debate, although conceptually it is an attractive concept. In patients after stent implantation with atrial fibrillation, in which a triple therapy with dual antiplatelet drugs and an anticoagulant is indicated, bleeding is an issue. Recent data suggest that administering a thienopyridine plus warfarin (or possibly a NOAC), while at the same time skipping aspirin may be an alternative to avoid severe bleeding and to maintain antithrombotic efficacy. Conclusion: An extensive therapeutic arsenal to interfere with clot formation requires an individualized approach considering the disease condition and co-morbidities of the patient, the anticoagulants’ and patient characteristics. This review builds on and extends previous publications of the authors on this topic.