Stroke reduction benefit of OAC outweighs high bleeding risk
History of bleeding and outcomes with apixaban versus warfarin in patients with atrial fibrillation in the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation trial
De Caterina R, Andersson U, Alexander JH, et al.
Am Heart J 2016;175:175-83
BackgroundIn patients with AF, the use of predictive algorithms for bleeding are recommended to guide clinical decision making regarding anticoagulation therapy [1,2]. The following scores are used for this purpose:
- HEMORR2HAGES (Hepatic or Renal Disease, Ethanol Abuse, Malignancy, Older Age, Reduced Platelet Count or Function, Re-Bleeding, Hypertension, Anemia, Genetic Factors, Excessive Fall Risk and Stroke) 
- HAS-BLED (Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile International Normalized Ratio, Elderly, Drugs/Alcohol) 
- ATRIA (Anticoagulation and Risk Factors in Atrial Fibrillation) 
Main resultsA history of clinically relevant or spontaneous bleeding was associated with:
- a 35% increase in risk for major bleeding (adjusted HR: 1.35; 95% CI: 1.14-1.61; P = 0.0008)
- a 48% increase in risk for major bleeding/clinically relevant non-major bleeding (adjusted HR: 1.48; 95% CI: 1.31-1.68; P = 0.001)
- increased risk of GUSTO mild bleeding: 7.7% vs 14.2 %; HR: 1.60; 95% CI: 1.46-1.77; P<0.001
- increased risk of ISTH minor bleeding: 5.2% vs 9.3%; HR: 1.58; 95% CI: 1.41-1.78; P<0.001
- similar risk of hemorrhagic stroke: 0.4% vs 0.3%; HR: 0.88; 95% CI: 0.52-1.49; P = 0.6215
- similar risk of intracranial bleeding: 0.6% vs 0.5%; HR: 0.90; 95% CI: 0.59-1.36; P = 0.6027
- similar risk of stroke or systemic embolism: 1.4% vs 1.5%; HR 0.97; 95% CI: 0.75-1.24; P = 0.7791
A history of GI bleeding was associated with an increased risk of bleeding during the trial:
- major bleeding adjusted HR: 1.97; 95% CI: 1.28-3.02
- major or clinically relevant non-major bleeding adjusted HR: 1.79; 95% CI: 1.29-2.50
Despite a history of any clinically relevant or spontaneous bleeding being associated with more major bleeding occurring consistently throughout the trial, apixaban was consistently associated with lower rates of major bleeding compared with warfarin in both patient groups with and without a history of bleeding.
ConclusionIn AF patients at increased risk for stroke, a history of bleeding was associated with a higher risk of major bleeding, with the exception of intracranial haemorrhage. The beneficial effects of apixaban over warfarin remained consistent regardless of history of bleeding. A history of bleeding was not associated with the risk of subsequent ischemic events.
Editorial comment In his editorial article, Goodman points out that the De Caterina et al analysis supports the concept in which the stroke reduction benefit of oral anticoagulation (OAC) outweighs the bleeding risk, even in patients with a history of bleeding. Moreover, he outlines physicians’ and patients’ perspectives on this topic: ‘Physicians tend to underestimate the risk of stroke and overestimate the risk of bleeding: we will only see the bleeds we “cause” and never the strokes we “prevented”, however,
Find this article online at American Heart Journal
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