TY - JOUR
T1 - Clinical outcomes and management associated with major bleeding in patients with atrial fibrillation treated with apixaban or warfarin
T2 - insights from the ARISTOTLE trial
AU - Held, Claes
AU - Hylek, Elaine M
AU - Alexander, John H
AU - Hanna, Michael
AU - Lopes, Renato D
AU - Wojdyla, Daniel M
AU - Thomas, Laine
AU - Al-Khalidi, Hussein
AU - Alings, Marco
AU - Xavier, Dennis
AU - Ansell, Jack
AU - Goto, Shinya
AU - Ruzyllo, Witold
AU - Rosenqvist, Mårten
AU - Verheugt, Freek W A
AU - Zhu, Jun
AU - Granger, Christopher B
AU - Wallentin, Lars
N1 - Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: [email protected].
PY - 2015/5/21
Y1 - 2015/5/21
N2 - AIM: In the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial, apixaban compared with warfarin reduced the risk of stroke, major bleed, and death in patients with atrial fibrillation. In this ancillary study, we evaluated clinical consequences of major bleeds, as well as management and treatment effects of warfarin vs. apixaban.METHODS AND RESULTS: Major International Society on Thrombosis and Haemostasis bleeding was defined as overt bleeding accompanied by a decrease in haemoglobin (Hb) of ≥2 g/dL or transfusion of ≥2 units of packed red cells, occurring at a critical site or resulting in death. Time to event [death, ischaemic stroke, or myocardial infarction (MI)] was evaluated by Cox regression models. The excess risk associated with bleeding was evaluated by separate time-dependent indicators for intracranial (ICH) and non-intracranial haemorrhage. Major bleeding occurred in 848 individuals (4.7%), of whom 126 (14.9%) died within 30 days. Of 176 patients with an ICH, 76 (43.2%) died, and of the 695 patients with major non-ICH, 64 (9.2%) died within 30 days of the bleeding. The risk of death, ischaemic stroke, or MI was increased roughly 12-fold after a major non-ICH bleeding event within 30 days. Corresponding risk of death following an ICH was markedly increased, with HR 121.5 (95% CI 91.3-161.8) as was stroke or MI with HR 21.95 (95% CI 9.88-48.81), respectively. Among patients with major bleeds, 20.8% received vitamin K and/or related medications (fresh frozen plasma, coagulation factors, factor VIIa) to stop bleeding within 3 days, and 37% received blood transfusion. There was no interaction between apixaban and warfarin and major bleeding on the risk of death, stroke, or MI.CONCLUSION: Major bleeding was associated with substantially increased risk of death, ischaemic stroke, or MI, especially following ICH, and this risk was similarly elevated regardless of treatment with apixaban or warfarin. These results underscore the importance of preventing bleeding in anti-coagulated patients. ClinicalTrials.gov Identifier: NCT00412984.
AB - AIM: In the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial, apixaban compared with warfarin reduced the risk of stroke, major bleed, and death in patients with atrial fibrillation. In this ancillary study, we evaluated clinical consequences of major bleeds, as well as management and treatment effects of warfarin vs. apixaban.METHODS AND RESULTS: Major International Society on Thrombosis and Haemostasis bleeding was defined as overt bleeding accompanied by a decrease in haemoglobin (Hb) of ≥2 g/dL or transfusion of ≥2 units of packed red cells, occurring at a critical site or resulting in death. Time to event [death, ischaemic stroke, or myocardial infarction (MI)] was evaluated by Cox regression models. The excess risk associated with bleeding was evaluated by separate time-dependent indicators for intracranial (ICH) and non-intracranial haemorrhage. Major bleeding occurred in 848 individuals (4.7%), of whom 126 (14.9%) died within 30 days. Of 176 patients with an ICH, 76 (43.2%) died, and of the 695 patients with major non-ICH, 64 (9.2%) died within 30 days of the bleeding. The risk of death, ischaemic stroke, or MI was increased roughly 12-fold after a major non-ICH bleeding event within 30 days. Corresponding risk of death following an ICH was markedly increased, with HR 121.5 (95% CI 91.3-161.8) as was stroke or MI with HR 21.95 (95% CI 9.88-48.81), respectively. Among patients with major bleeds, 20.8% received vitamin K and/or related medications (fresh frozen plasma, coagulation factors, factor VIIa) to stop bleeding within 3 days, and 37% received blood transfusion. There was no interaction between apixaban and warfarin and major bleeding on the risk of death, stroke, or MI.CONCLUSION: Major bleeding was associated with substantially increased risk of death, ischaemic stroke, or MI, especially following ICH, and this risk was similarly elevated regardless of treatment with apixaban or warfarin. These results underscore the importance of preventing bleeding in anti-coagulated patients. ClinicalTrials.gov Identifier: NCT00412984.
KW - Atrial Fibrillation/complications
KW - Factor Xa Inhibitors/administration & dosage
KW - Female
KW - Follow-Up Studies
KW - Hemorrhage/chemically induced
KW - Humans
KW - Intracranial Hemorrhages/chemically induced
KW - Male
KW - Middle Aged
KW - Myocardial Infarction/etiology
KW - Pyrazoles/administration & dosage
KW - Pyridones/administration & dosage
KW - Stroke/mortality
KW - Thromboembolism/mortality
KW - Treatment Outcome
KW - Warfarin/administration & dosage
U2 - 10.1093/eurheartj/ehu463
DO - 10.1093/eurheartj/ehu463
M3 - Article
C2 - 25499871
SN - 0195-668X
VL - 36
SP - 1264
EP - 1272
JO - European Heart Journal
JF - European Heart Journal
IS - 20
ER -