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There are several disorders which carry an increased risk of thrombosis, clots that interfere with normal circulation, including: venous thromboembolism (VTE), comprising both deep vein thrombosis (DVT) and pulmonary embolism (PE), atrial fibrillation (AF), acute coronary syndromes (ACS), valve disease and endocarditis, and conditions associated with a raised risk of ischemic stroke. Due to this increased risk, a number of thromboprophylactic medications target the coagulation cascade. Effective anticoagulation can be achieved by inhibiting different coagulation factors in the coagulation cascade.

Anticoagulation can be achieved by inhibition of the various coagulation factors. Non-VKA oral anticoagulant (NOAC) development has focused on the synthesis of selective inhibitors of coagulation factors, preferably acting independently of cofactors. The NOACs act on a number of targets in the coagulation cascade, but two of its key factors, Xa and IIa (thrombin), are the major therapeutic targets. As they are involved in the final steps of the coagulation cascade, their inhibition allows blocking of both intrinsic and extrinsic coagulation pathways.

Factor Xa represents an attractive target for antithrombotic drugs as blockade of factor Xa permits inhibition of both the extrinsic and intrinsic coagulation pathways. Several factor Xa inhibitors, such as rivaroxaban, apixaban and edoxaban, have been approved for certain conditions, and are also in clinical development for other indications.

The number of available non-VKA oral anticoagulants (NOACs) has provided clinicians with a greater range of options for the management of patients with thromboembolic disorders. Recently, two meta-analyses compared the efficacy and safety of the NOACs in stroke prevention in patients with atrial fibrillation (AF) [1] and the prevention of recurrent venous thromboembolism (VTE) [2]. These meta-analyses were the first to include data for all four NOACs studied in pivotal phase III studies for these indications.