 Clinically significant bleeding will be a composite of major and non-major clinically significant bleeding. Clinically significant major bleeding will be defined according to the criteria of the International Society on Thrombosis and Hemostasis ISTH, as clinically overt bleeding accompanied by one or more of the following: a decrease in hemoglobin level 20 gl over a 24-hour period, transfusion of 2 or more units of packed red cells, bleeding at a critical site intracranial, intraspinal, intraocular, pericardial, intramuscular with compartment syndrome, or retroperitoneal, or fatal bleeding. 18 This definition is the same as that used recently in all trials comparing NOAC with warfarin. Clinically significant non-major bleeding will be defined similarly as it was in the ROCKET trial, i.e., any bleeding requiring hospitalization or invasive procedure, which doesn t meet the ISTH major criteria. 