Oral anticoagulant therapy in atrial fibrillation patients at high stroke and bleeding risk.

Atrial fibrillation (AF) is associated with a 5-fold greater risk of ischemic stroke or systemic embolism compared with normal sinus rhythm. Cardioembolic AF-related strokes are often more severe, fatal or associated with greater permanent disability and higher recurrence rates than strokes of other aetiologies. These strokes may be effectively prevented with oral anticoagulant (OAC) therapy, using either vitamin K antagonists (VKAs) or non-vitamin K antagonist OACs (NOACs) such as the direct thrombin inhibitor dabigatran or direct factor Xa inhibitors rivaroxaban, apixaban or edoxaban. Most AF patients have a positive net clinical benefit from OAC, excluding those with AF and no conventional stroke risk factors. Balancing the risks of stroke and bleeding is necessary for optimal use of OAC in clinical practice, and modifiable bleeding risk factors must be addressed. Concerns remain over 'non-changeable' bleeding risk factors such as older age, significant renal or hepatic impairment, prior stroke(s) or prior bleeding event(s) and active malignancies. Such AF patients are often termed 'special' AF populations, due to their 'special' risk profile that includes increased risks of both thromboembolic and bleeding events, and due to fear of bleeding complications these AF patients are often denied OAC. Evidence shows, however, that the absolute benefits of OAC are the greatest in patients at the highest risk, and NOACs may offer even a greater net clinical benefit compared to warfarin particularly in these high risk patients. In this review article, we summarize available data on stroke prevention in AF patients at increased risk of both stroke and bleeding and discuss the use of NOACs for thromboprophylaxis in these 'special' AF populations.