Based on the established fact that anticoagulation with warfarin is superior to antiplatelet agents in the prevention of thromboembolic events in atrial fibrillation (AF), we propose that, in contrast to atherothrombotic disorders, the risk of developing a stroke or thromboembolic event in AF is more likely to be affected by the coagulation pathway than by platelet activity. Indeed, platelet-rich thrombi may be the predominant underlying pathophysiological process in coronary artery disease patients, thus representing an entirely different prothrombotic profile to the patients with AF, where clotting factor abnormalities (and thus fibrin-rich thrombi) are more likely. Thus, we would hypothesise that warfarin is probably more likely to be more beneficial than aspirin-clopidogrel combination therapy when used in this setting. Indeed, this hypothesis would need to be tested in large randomised clinical trials.