BAY2433334

CV death included death due to stroke, MI, heart failure or cardiogenic shock, sudden death or any other death due to other cardiovascular causes. Death due to non-traumatic hemorrhage was included. Acute MI was used when there was evidence of myocardial necrosis in a clinical setting consistent with acute myocardial ischemia. Stroke was defined as an acute episode of focal or global neurological dysfunction caused by an injury of the brain, spinal cord, or retina as a result of hemorrhage or infarction. ST was defined incorporating diagnostic certainty as well as timing: "Definite" ST: The highest level of certainty. Either angiographic or pathological confirmation of stent thrombosis. "Probable" ST: Regardless of the time after the index procedure, any MI that is related to documented acute ischemia in the territory of the implanted stent without angiographic confirmation of stent thrombosis and in the absence of any other obvious cause

Type 2: any overt, actionable sign of hemorrhage that doesn't fit the criteria for type 3 or 5 but meets at least one of the following criteria: 1) requires nonsurgical, med intervention by a HCP, 2) leads to hospital or rise in level of care, or 3) prompt eval. Type 3a: 1) overt bleed + Hg drop of 3 to \<5 g/dl (provided Hg drop is related to bleed); 2 any transfusion with overt bleed. Type 3b: 1) overt bleed + Hg drop ≥5 g/dL (provided Hg drop is related to bleed); 2) cardiac tamponade; 3) bleed requiring surgical intervention for control (exclude dental/nasal /skin/hemorrhoid); 4) bleed requiring IV vasoactive agents. Type 3c: 1) ICH hemorrhage (doesn't include microbleeds or HT, does include intraspinal); subcategories confirmed by autopsy or imaging or LP; 2) intraocular bleed compromising vision. Type 5: fatal bleed. Type 5a: probable fatal bleed; no autopsy or image confirmation but clinical suspicion. Type 5b: definite fatal bleed; overt bleed or autopsy or image confirmation.

Ischemic stroke was defined as either of : 1) Rapid onset (or present on awakening) of a new focal neurological deficit with clinical (\>24 hours symptoms/signs) or imaging evidence of infarction that was not attributable to a non-ischemic cause; 2) Acute worsening of an existing focal neurological deficit that was judged to be attributable to a new infarction or extension of the previous infarction in the same vascular territory, based on persisting symptoms/signs or imaging evidence of infarction and no evidence of a non-ischemic etiology. If imaging was inconclusive, persistent symptoms/signs must be significant (worsening of NIHSS score of 4 or more) and sustained (duration of ≥24 hours or until death). Covert brain infarcts were defined as incident infarcts detected by serial MRI in the absence of an adjudicated stroke consistent with the location of the infarct. MRI criteria for brain infarction were available in the MRI procedures manual.

ISTH Major Bleeding criteria: 1. Fatal bleeding, and/or 2. Symptomatic bleeding in a critical area or organ (intracranial, intraocular, intraspinal, pericardial, retroperitoneal, intraarticular, or intramuscular with compartment syndrome), and/or 3. Clinically overt bleeding associated with a recent decrease in the hemoglobin level of ≥ 2 g/dL (20 g/L; 1.24 mmol/L) compared to the most recent hemoglobin value available before the event, and/or 4. Clinically overt bleeding leading to transfusion of 2 or more units of packed red blood cells or whole blood. ISTH Clinically Relevant Non-Major Bleeding is considered any sign or symptom of hemorrhage that does not fit the criteria for the ISTH definition of major bleeding, but does meet at least one of the following criteria 1. requiring medical intervention by a healthcare professional. 2. leading to hospitalization or increased level of care. 3. prompting a face to face (i.e. not just a telephone or electronic communication) evaluation.

ISTH Major Bleeding criteria: 1. Fatal bleeding, and/or 2. Symptomatic bleeding in a critical area or organ (intracranial, intraocular, intraspinal, pericardial, retroperitoneal, intraarticular, or intramuscular with compartment syndrome), and/or 3. Clinically overt bleeding associated with a recent decrease in the hemoglobin level of ≥ 2 g/dL (20 g/L; 1.24 mmol/L) compared to the most recent hemoglobin value available before the event, and/or 4. Clinically overt bleeding leading to transfusion of 2 or more units of packed red blood cells or whole blood. ISTH Clinically Relevant Non-Major Bleeding is considered any sign or symptom of hemorrhage that does not fit the criteria for the ISTH definition of major bleeding, but does meet at least one of the following criteria 1. requiring medical intervention by a healthcare professional. 2. leading to hospitalization or increased level of care. 3. prompting a face to face (i.e. not just a telephone or electronic communication) evaluation.