Why the study?
The study aimed to evaluate whether adding CYP2C9 and VKORC1 genotype bins to the HAS-BLED score improves bleeding risk prediction in warfarin-treated patients with AF.
Does the addition of genotype bins to the HAS-BLED score improve bleeding risk prediction in warfarin-treated patients with atrial fibrillation?
Does the addition of genotype bins to the HAS-BLED score improve bleeding risk prediction in warfarin-treated patients with atrial fibrillation?
The addition of CYP2C9 and VKORC1 genotype bins to the HAS-BLED score significantly improves the prediction of clinically relevant and major bleeding in warfarin-treated patients with atrial fibrillation.
Adding genotype bins may refine HAS-BLED bleeding prediction in warfarin-treated AF; hypothesis-generating pending prospective validation.
Background. This study aimed to analyse the role of the HAS-BLED score with the addition of genotype bins for bleeding risk prediction in warfarin-treated patients with atrial fibrillation (AF). Methods and Results. Consecutive patients with AF on initial warfarin treatment were recruited. For each patient, CYP2C9 <a:math xmlns:a="http://www.w3.org/1998/Math/MathML" id="M1"> <a:msup> <a:mrow/> <a:mrow> <a:mi>∗</a:mi> </a:mrow> </a:msup> </a:math> 3 and VKORC1-1639 A/G genotyping was performed to create 3 genotype functional bins. The predictive values of the HAS-BLED score with or without the addition of genotype bins were compared. According to the carrier status of the genotype bins, the numbers of normal, sensitive, and highly sensitive responders among 526 patients were 64 (12.17%), 422 (80.23%), and 40 (7.60%), respectively. A highly sensitive response was independently associated with clinically relevant bleeding (HR: 3.85, 95% CI: 1.88–7.91, <c:math xmlns:c="http://www.w3.org/1998/Math/MathML" id="M2"> <c:mi>P</c:mi> <c:mo>=</c:mo> <c:mn>0.001</c:mn> </c:math> ) and major bleeding (HR:3.75, 95% CI: 1.17–11.97, <e:math xmlns:e="http://www.w3.org/1998/Math/MathML" id="M3"> <e:mi>P</e:mi> <e:mo>=</e:mo> <e:mn>0.03</e:mn> </e:math> ). With the addition of genotype bins, the performance of the HAS-BLED score for bleeding risk prediction was significantly improved (c-statistic from 0.60 to 0.64 for clinically relevant bleeding and from 0.64 to 0.70 for major bleeding, <g:math xmlns:g="http://www.w3.org/1998/Math/MathML" id="M4"> <g:mi>P</g:mi> <g:mo><</g:mo> <g:mn>0.01</g:mn> </g:math> ). Using the integrated discriminatory, net reclassification improvement, and decision curve analysis, the HAS-BLED score plus genotype bins could perform better in predicting any clinically relevant bleeding than the HAS-BLED score alone. Conclusions. Genotypes have an incremental predictive value when combined with the HAS-BLED score for the prediction of clinically relevant bleeding in warfarin-treated patients with AF.
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Liu et al. (2021) studied this question.
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