For patients who were not receiving VKA therapy at study entry, VKA therapy was associated with a nonsigni cant trend toward a 69% relative increase in major bleeding compared with dual antiplatelet therapy, whereas in patients already receiving VKA therapy at study entry, VKA therapy was associated with a nonsigni cant trend toward a 24% relative decrease in major bleeding compared with dual antiplatelet therapy. 2.1.5 Dual Antiplatelet Therapy With Aspirin and Clopidogrel vs Aspirin Alone: The ACTIVE A study compared combination aspirin and clopid- ogrel therapy with aspirin alone.81 The trial enrolled 7,554 patients considered unsuitable for VKA therapy (approximately one-half because of a physician s judg- ment that VKA was inappropriate, one-fourth because of a speci c risk of bleeding, and one-fourth because of the patient s preference not to take a VKA as the sole reason) and found that combination therapy is more effective in reducing the risk of nonfatal stroke in patients with AF but also increases the risk of non- fatal major extracranial bleeds compared with treat- ment with aspirin alone (Table 7). 2.1.6 New Oral Anticoagulants vs VKAs: Anti- thrombotic therapy for AF is evolving rapidly because of the development of new oral anticoagulants that directly target different parts of the coagulation path- way, have a more predictable anticoagulant effect, and do not require INR monitoring. Included in this new group of drugs are direct thrombin inhibitors (eg, dabigatran) and direct factor Xa inhibitors (apixa- ban, rivaroxaban, edoxaban). Results of large phase 3 clinical trials of these agents in patients with AF have been recently published or will be reported soon (Table 8). 