Definition of major bleeding complication and use of antiplatelet agents
| Study name | Major bleeding complication definition | Antiplatelet agent |
|---|---|---|
| Venous thromboembolism prophylaxis | ||
| EXULT A7 | Occurrence of at least one of the following: | Not allowed |
| 1. Critical site (intracranial, retroperitoneal, intraocular, intraspinal, pericardial) | ||
| 2. Bleeding index ≥2.0 (difference between baseline and postbleeding haemoglobin level (g/l) plus number of packed cells or whole blood transfusion | ||
| 3. Need for medical or surgical intervention at operative site | ||
| 4. Fatal | ||
| EXULT B8 | Not clearly stated | Not allowed |
| RE-NOVATE9 | Acute overt clinical bleeding with one of the following: | Aspirin dose <162 mg daily permitted |
| 1. Critical site (intracranial, retroperitoneal, intraocular, intraspinal, pericardial) | ||
| 2. Fall in haemoglobin ≥20 g/l in excess of that expected by investigator | ||
| 3. Transfusion ≥2 units of packed cells or whole blood in excess of that expected by investigator | ||
| 4. Leading to re-operation | ||
| 5. Warranting treatment cessation | ||
| 6. Fatal | ||
| RE-MODEL10 | As in RE-NOVATE | Aspirin dose <160 mg daily permitted |
| RE-MOBILIZE11 | Occurrence of at least one of the following: | Aspirin dose <160 mg |
| 1. Symptomatic intracranial, retroperitoneal, intraocular or intraspinal bleeding | daily permitted | |
| 2. Clinically overt bleeding with fall of haemoglobin ≥2.0 g/dl and/or leading to transfusion of ≥2 units of packed cells or whole blood | ||
| 3. Need for treatment cessation or surgical intervention at operative site | ||
| 4. Fatal | ||
| RE-NOVATE II12 | As in RE-NOVATE | Aspirin dose <162 mg daily permitted |
| RECORD113 | Occurrence of at least one of the following: | Not mentioned |
| 1. Intracranial, retroperitoneal, intraocular or intraspinal bleeding | ||
| 2. Clinically overt bleeding with fall of haemoglobin ≥2.0 g/dl | ||
| 3. Transfusion of ≥2 units of packed cells or whole blood | ||
| 4. Need for surgical intervention at operative or bleeding site | ||
| 5. Fatal | ||
| RECORD214 | Occurrence of at least one of the following: | Not mentioned |
| 1. Critical site bleeding; for example, intracranial, retroperitoneal, intraocular or intraspinal | ||
| 2. Clinically overt bleeding with fall of haemoglobin ≥2.0 g/dl (calculated from first post-operative level) | ||
| 3. Transfusion of ≥2 units of packed cells or whole blood | ||
| 4. Need for surgical intervention at operative or bleeding site | ||
| 5. Fatal | ||
| RECORD315 | Occurrence of at least one of the following: | not mentioned |
| 1. Critical organ bleeding | ||
| 2. Clinically overt bleeding with fall of haemoglobin ≥2.0 g/dl | ||
| 3. Transfusion of ≥2 units of packed cells or whole blood | ||
| 4. Need for reoperation | ||
| 5. Fatal | ||
| RECORD416 | Clinically overt bleeding: | not mentioned |
| 1. In critical organ; for example, intracranial, retroperitoneal, intraocular or intraspinal | ||
| 2. Fall of haemoglobin ≥2.0 g/dl (calculated from postoperative level) | ||
| 3. Transfusion of ≥2 units of blood | ||
| 4. Need for operation | ||
| 5. Fatal | ||
| ADVANCE 117 | Acute overt clinical bleeding with one of the following: | not allowed |
| 1. Critical site (intracranial, retroperitoneal, intraocular, intraspinal, pericardial) | ||
| 2. Fall in haemoglobin ≥2 g/dl within 24 h | ||
| 3. Transfusion ≥2 units of packed cells | ||
| 4. Need for surgical intervention at operative site | ||
| 5. Intramuscular bleeding with compartment syndrome | ||
| 6. Fatal | ||
| ADVANCE 218 | As in ADVANCE 1 | Not allowed |
| ADVANCE 319 | As in ADVANCE 1 | Not allowed |
| Treatment of venous thromboembolism | ||
| THRIVE20 | Clinically overt bleeding: | Aspirin at lowest |
| 1. In critical sites | effective dose | |
| 2. Fall of haemoglobin ≥2.0 g/dl | permitted | |
| 3. Transfusion of ≥2 units of blood or packed cells | ||
| 4. Fatal | ||
| RE-COVER21 | Clinically overt bleeding: | Aspirin ≤100 mg daily |
| 1. In critical sites | permitted | |
| 2. Fall of haemoglobin ≥20 g/l | ||
| 3. Transfusion of ≥2 units of blood or packed cells | ||
| 4. Fatal | ||
| RE-SONATE22 | Not stated | Not stated |
| REMEDY23 | Not stated | Not stated |
| EINSTEIN24 | Clinically overt bleeding: | Aspirin ≤100 mg daily |
| 1. In critical sites; for example, intracranial and retroperitoneal | or clopidogrel 75 mg | |
| 2. Fall of haemoglobin ≥20 g/l | daily, or both, were | |
| 3. Transfusion of ≥2 units of blood or packed cells | permitted | |
| 4. Fatal | ||
| Prevention of embolic events in atrial fibrillation | ||
| SPORTIF III25 | Occurrence of at least one of the following: | Aspirin ≤100 mg |
| 1. Intracranial, retroperitoneal, intraocular, intraspinal, pericardial or atraumatic intra-articular bleeding | daily permitted (21%)* | |
| 2. Clinically overt bleeding with fall of haemoglobin ≥20 g/l | ||
| 3. Transfusion of ≥2 units of erythrocytes or whole blood | ||
| 4. Fatal | ||
| SPORTIF V26 | As in SPORTIF III | As in SPORTIF III (18%)* |
| RE-LY27 | Occurrence of at least one of the following: | Aspirin <100 mg daily |
| 1. Critical area or organ bleeding; for example, intracranial | or antiplatelet agent | |
| 2. Clinically overt bleeding with fall of haemoglobin ≥20 g/l | permitted (40%)* | |
| 3. Transfusion of ≥2 units of blood | ||
| 4. Need for surgery | ||
| 5. Fatal | ||
| ROCKET AF28 | Clinically overt bleeding: | Aspirin ≤100 mg daily |
| 1. In critical anatomic site; for example, intracranial, retroperitoneal, ocular, spinal, pericardial, articular or intramuscular with compartment syndrome | or monothienpyridine therapy permitted | |
| 2. Fall of haemoglobin ≥2.0 g/dl | (38.5%)* | |
| 3. Transfusion of ≥2 units of whole blood or packed cells | ||
| 4. Permanent disability | ||
| 5. Fatal | ||
| AVERROES29 | Clinically overt bleeding: | Thienopyridine therapy |
| 1. In critical sites; for example, intracranial, retroperitoneal, ocular, spinal, pericardial, articular or intramuscular with compartment syndrome | permitted if needed | |
| 2. Fall of haemoglobin ≥2.0 g/dl | ||
| 3. Transfusion of ≥2 units of packed cells | ||
| 4. Fatal | ||
| ARISTOTLE30 | Clinically overt bleeding: | Aspirin ≤165 mg daily |
| 1. In critical sites | or monothienopyridine | |
| 2. Fall of haemoglobin ≥2.0 g/dl over a 24 h period | permitted (32%)* | |
| 3. Transfusion of ≥2 units of packed cells | ||
| 4. Fatal | ||
| Treatment of acute coronary syndrome | ||
| RE-DEEM31 | Occurrence of one of the following: | All patients receiving |
| 1. Bleeding in critical sites; for example, intracranial, retroperitoneal, ocular, spinal, pericardial, articular or intramuscular with compartment syndrome | dual antiplatelet agents | |
| 2. Fall of haemoglobin ≥2.0 g/dl | ||
| 3. Transfusion of ≥2 units of packed cells or whole blood | ||
| 4. Fatal | ||
| ATLAS ACS 2 | Occurrence of one of the following: | All patients received |
| TIMI 5132 | 1. Fall of haemoglobin ≥5.0 g/dl or haematocrit >15% | low-dose aspirin and |
| 2. Intracranial haemorrhage | thienopyridine permitted | |
| APPRAISE33 | Occurrence of one of the following: | All patients received |
| 1. Bleeding in critical sites; for example, intracranial, retroperitoneal, ocular, spinal, pericardial, articular or intramuscular with compartment syndrome | aspirin ≤165 mg daily and thienopyridine | |
| 2. Fall of haemoglobin ≥2.0 g/dl | therapy permitted | |
| 3. Transfusion of ≥2 units of packed cells or whole blood | ||
| 4. Fatal | ||
| APPRAISE 234 | Occurrence of one of the following: | Use of aspirin and |
| 1. Fall of haemoglobin ≥5.0 g/dl or haematocrit >15% | thienopyridine | |
| 2. Intracranial haemorrhage | permitted | |
*Proportion receiving antiplatelet therapy.
Please refer to footnote of table 1 for acronyms.