title: Major Bleeding in Patients with Non-Valvular Atrial Fibrillation: Impact of Time in Therapeutic Range on Contemporary Bleeding Risk Scores.
abstract: Bleeding risk represents a major concern in anticoagulated patients with atrial fibrillation (AF). Several bleeding prediction scores have been described: HAS-BLED, ATRIA, HEMORR2HAGES and ORBIT. Of these, only HAS-BLED considers quality of anticoagulation control amongst vitamin K antagonist (VKA) users. We hypothesised that predictive value of bleeding risk scores other than HAS-BLED could be improved incorporating time in therapeutic range (TTR) in warfarin-treated patients. Of the 127 adjudicated major bleeding events, 21.3% of events occurred in 'low-risk' HAS-BLED category (1.8 per 100 patient-years), compared to higher proportions (≥50% of events; ~2.5 per 100 patient-years) in 'low-risk' categories for other scores. Only the 'low-risk' HAS-BLED category was associated with the absence of investigator-defined major bleeding events (OR: 1.46;95% CI: 1.00-2.15). 'High' or 'medium/high' risk categories for the HAS-BLED (p = 0.023) or ORBIT (p = 0.022) scores, respectively, conferred significant risk for adjudicated major bleeding events. On Cox regression analysis, adjudicated major bleeding was associated only with HAS-BLED (HR: 1.62;95% CI: 1.06-2.48) and ORBIT (HR: 1.83;95% CI: 1.08-3.09) 'high-risk' categories. Adding 'labile INR' (TTR < 65%) to ORBIT, ATRIA and HEMORR2HAGES significantly improved their reclassification and discriminatory performances. In conclusion, HAS-BLED categorised adjudicated major bleeding events in low-risk and high-risk patients appropriately, whilst ORBIT and ATRIA categorised most major bleeds into their 'low-risk' patient categories. Adding TTR to ORBIT, ATRIA and HEMORR2HAGES led to improved predictive performance for major bleeding.
authors.affiliation: University of Birmingham Institute of Cardiovascular Sciences, City Hospital, Birmingham, United Kingdom.|Department of Internal Medicine and Medical Specialties, Sapienza-University of Rome, Rome, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Proietti
authors.affiliation: University of Birmingham Institute of Cardiovascular Sciences, City Hospital, Birmingham, United Kingdom.
authors.forename: Keitaro
authors.initials: K
authors.lastname: Senoo
authors.affiliation: University of Birmingham Institute of Cardiovascular Sciences, City Hospital, Birmingham, United Kingdom.
authors.forename: Deirdre A
authors.initials: DA
authors.lastname: Lane
authors.affiliation: University of Birmingham Institute of Cardiovascular Sciences, City Hospital, Birmingham, United Kingdom.|Aalborg Thrombosis Research Unit, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.
authors.forename: Gregory Y H
authors.initials: GY
authors.lastname: Lip
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000009:adverse effects* / Q000627:therapeutic use; D001281:Atrial Fibrillation / Q000150:complications* / Q000188:drug therapy; D003661:Decision Support Techniques; D005260:Female; D006470:Hemorrhage / Q000175:diagnosis* / Q000473:pathology*; D006801:Humans; D008297:Male; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D013997:Time Factors; D014859:Warfarin / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D000925:Anticoagulants; D014859:Warfarin