Objectives Current international guidelines advocate the application of bleeding risk scores only to identify modifiable risk factors, but not to withhold treatment in patients at high risk of bleeding. VTE-BLEED (ActiVe cancer, male with uncontrolled hyperTension, anaEmia, history of BLeeding, agE and rEnal Dysfunction) is a simple bleeding risk score that predicts major bleeding (MB) in patients with venous thromboembolism, but has never been evaluated in patients with atrial fibrillation (AF). We sought to evaluate VTE-BLEED in patients with AF included in the Randomised Evaluation of Long-term anticoagulant therapY (RE-LY) trial, to assess whether score classes (high vs low bleeding risk) interact with the tested dabigatran doses (150 vs 110 mg twice daily), and to investigate whether dose reductions based on this interaction might help to lower the incidence of the composite outcome MB, stroke/systemic embolism or death.
Methods The score was calculated in the safety population of RE-LY (n=18 040) and recalibrated for AF (AF-adapted VTE-BLEED or AF-BLEED). HRs were calculated to evaluate the score’s predictive accuracy for MB. The risk ratios (RRs) for the composite outcome comparing dabigatran 150 and 110 mg twice daily were calculated for the high-risk group.
Results AF-BLEED classified 3534 patients (19.6%) at high bleeding risk, characterised by a 2.9-fold to 3.4-fold higher risk of bleeding than low bleeding risk patients, across the treatment arms. High bleeding risk patients randomised to 110 mg twice daily had a lower incidence of the composite outcome than those randomised to 150 mg twice daily, for an RR of 0.52 (95% CI 0.35 to 0.78). Compared with the label criteria for dose reduction, AF-BLEED identified an additional 11% of patients who might have benefited from dose reduction.
Conclusions AF-BLEED identified patients with AF at high risk of bleeding. Our findings raise the hypothesis that dabigatran 110 mg twice daily might be considered in patients classified as high risk according to the AF-BLEED score. This study provides a basis for future studies to explore safe dose reductions of direct oral anticoagulants in selected patient groups based on bleeding scores.
- atrial fibrillation
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Contributors The authors have reviewed and approved the submission of this manuscript. FAK and MVH were responsible for the conception of the research. GK-BC, LV, SJvdW, SB and FAK drafted the manuscript. LV performed the data analysis. LV, GK-BC, SJvdW, SB and FAK interpreted the data. SK and MVH reviewed and revised the manuscript.
Funding This RE-LY trial was funded by Boehringer Ingelheim, Ingelheim, Germany. No specific funding was related to the present study.
Competing interests SB reports congress and travel payments from Daiichi-Sankyo and Bayer HealthCare, and lecture honoraria from EKOS Corporation/BTG. SK reports having received consultancy and lecture honoraria from Bayer, Boehringer Ingelheim, Daiichi-Sankyo, MSD and Pfizer—Bristol-Myers Squibb, and institutional grants from Actelion, Bayer, Boehringer Ingelheim, Daiichi-Sankyo and Pfizer—Bristol-Myers Squibb. MVH reports grants from ZonMW Dutch Healthcare Fund, grants and personal fees from Boehringer Ingelheim, grants and personal fees from Pfizer-BMS, grants and personal fees from Bayer Health Care, grants from Aspen, grants and personal fees from Daiichi-Sankyo, outside the submitted work. FAK reports research grants from Bayer, Bristol-Myers Squibb, Boehringer-Ingelheim, Daiichi-Sankyo, MSD and Actelion, the Dutch Heart Foundation and the Dutch Thrombosis Association, outside the submitted work
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Patient consent for publication Not required.
Ethics approval The RE-LY study was approved by all appropriate national regulatory authorities and ethics committees of the participating centres. For the RE-LY study, patients had to provide written informed consent prior to participation. This post hoc analysis of the RE-LY study did not require approval from an ethics committee. The research proposal for this study was submitted to www.clinicalstudydatarequest.com for review and access to anonymised individual patient data from RE-LY was provided.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement Data may be obtained from a third party and are not publicly available. Not available. Unique identifier: NCT0026260.
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