Patients with atrial utter As in 2.1 As in 2.1 - Death - All stroke - Ischemic stroke - Systemic embolism - Intracranial hem- orrhage (subdural, subarachnoid, and intracerebral) - Major extracranial hemorrhage - MI - Vascular death SR RCTs Cohort studies 6.1 Risk factors for bleeding on OAC therapy What are the risk factors for bleeding while on VKA therapy? Patients with AF on VKA therapy NA NA - Fatal hemorrhage - Intracranial hem- orrhage (subdural, subarachnoid, intracerebral) - Major extracranial hemorrhage - Minor bleeding Epidemiologic studies Cohort studies RCTs 6.2 Bleeding risk assessment What risk strati cation schemes most accurately predict the risk of bleeding? Patients with AF on OAC therapy NA NA C-statistic NRI, IDI, DCA Absolute rates of bleeding outcomes (as listed above) Clinical prediction rules 7 The patient What are the values and preferences of patients with AF regarding VKA therapy, risk of stroke, and risk of bleeding? Patients with AF NA NA Patient preferences Factors which affect patient preferences Quality of life RCTs Observational studies ACS acute coronary syndrome; AF atrial brillation; DCA decision curve analysis; ICH intracranial hemorrhage; IDI integrated discrimination index; INR international normalized ratio; LMWH low- molecular-weight heparin; MI myocardial infarction; NA not available; NOAC non-vitamin K antagonist oral anticoagulant drug; NRI net reclassi cation index; OAC oral anticoagulant; RCT randomized controlled trial; SR systematic reviews; TE thromboembolism; TEE transesophageal echocardiography; TTR time within therapeutic range; VKA vitamine K antagonist. 