uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
The novel biomarker-based ABC (age, biomarkers, clinical history)-bleeding risk score for patients with atrial fibrillation: a derivation and validation study
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
Duke Med, Duke Clin Res Inst, Durham, NC USA..
Show others and affiliations
2016 (English)In: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 387, no 10035, 2302-2311 p.Article in journal (Refereed) Published
Abstract [en]

Background: The benefit of oral anticoagulation in atrial fibrillation is based on a balance between reduction in ischaemic stroke and increase in major bleeding. We aimed to develop and validate a new biomarker-based risk score to improve the prognostication of major bleeding in patients with atrial fibrillation.

Methods: We developed and internally validated a new biomarker-based risk score for major bleeding in 14 537 patients with atrial fibrillation randomised to apixaban versus warfarin in the ARISTOTLE trial and externally validated it in 8468 patients with atrial fibrillation randomised to dabigatran versus warfarin in the RE-LY trial. Plasma samples for determination of candidate biomarker concentrations were obtained at randomisation. Major bleeding events were centrally adjudicated. The predictive values of biomarkers and clinical variables were assessed with Cox regression models. The most important variables were included in the score with weights proportional to the model coefficients. The ARISTOTLE and RE-LY trials are registered with ClinicalTrials.gov, numbers NCT00412984 and NCT00262600, respectively.

Findings: The most important predictors for major bleeding were the concentrations of the biomarkers growth differentiation factor-15 (GDF-15), high-sensitivity cardiac troponin T (cTnT-hs) and haemoglobin, age, and previous bleeding. The ABC-bleeding score (age, biomarkers [GDF-15, cTnT-hs, and haemoglobin], and clinical history [previous bleeding]) score yielded a higher c-index than the conventional HAS-BLED and the newer ORBIT scores for major bleeding in both the derivation cohort (0.68 [95% CI 0.66-0.70] vs 0.61 [0.59-0.63] vs 0.65 [0.62-0.67], respectively; ABC-bleeding vs HAS-BLED p< 0.0001 and ABC-bleeding vs ORBIT p= 0.0008). ABC-bleeding score also yielded a higher c-index score in the the external validation cohort (0.71 [95% CI 0.68-0.73] vs 0.62 [0.59-0.64] for HAS-BLED vs 0.68 [0.65-0.70] for ORBIT; ABC-bleeding vs HAS-BLED p< 0.0001 and ABC-bleeding vs ORBIT p= 0.0016). A modified ABC-bleeding score using alternative biomarkers (haematocrit, cTnI-hs, cystatin C, or creatinine clearance) also outperformed the HAS-BLED and ORBIT scores.

Interpretation: The ABC-bleeding score, using age, history of bleeding, and three biomarkers (haemoglobin, cTn-hs, and GDF-15 or cystatin C/CKD-EPI) was internally and externally validated and calibrated in large cohorts of patients with atrial fibrillation receiving anticoagulation therapy. The ABC-bleeding score performed better than HAS-BLED and ORBIT scores and should be useful as decision support on anticoagulation treatment in patients with atrial fibrillation.

Place, publisher, year, edition, pages
2016. Vol. 387, no 10035, 2302-2311 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-302217DOI: 10.1016/S0140-6736(16)00741-8ISI: 000376969100033PubMedID: 27056738OAI: oai:DiVA.org:uu-302217DiVA: diva2:956946
Available from: 2016-08-31 Created: 2016-08-31 Last updated: 2016-08-31Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Hijazi, ZiadOldgren, JonasLindbäck, JohanHeld, ClaesSiegbahn, AgnetaWallentin, Lars
By organisation
CardiologyUCR-Uppsala Clinical Research CenterDepartment of Medical Sciences
In the same journal
The Lancet
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 28 hits
ReferencesLink to record
Permanent link

Direct link