Enhancing the 'real world' prediction of cardiovascular events and major bleeding with the CHA(2)DS(2)-VASc and HAS-BLED scores using multiple biomarkers

Background: Atrial fibrillation (AF)-European guidelines suggest the use of biomarkers to stratify patients for stroke and bleeding risks. We investigated if a multibiomarker strategy improved the predictive performance of CHA(2)DS(2)-VASc and HAS-BLED in anticoagulated AF patients. Methods: We included consecutive patients stabilized for six months on vitamin K antagonists (INRs 2.0-3.0). High sensitivity troponin T, NT-proBNP, interleukin-6, von Willebrand factor concentrations and glomerular filtration rate (eGFR; using MDRD-4 formula) were quantified at baseline. Time in therapeutic range (TTR) was recorded at six months after inclusion. Patients were follow-up during a median of 2375 (IQR 1564-2887) days and all adverse events were recorded. Results: In 1361 patients, adding four blood biomarkers, TTR and MDRD-eGFR, the predictive value of CHA(2)DS(2)-VASc increased significantly by c-index (0.63 vs. 0.65; p=.030) and IDI (0.85%; p<.001), but not by NRI (-2.82%; p<.001). The predictive value of HAS-BLED increased up to 1.34% by IDI (p<.001). Nevertheless, the overall predictive value remains modest (c-indexes approximately 0.65) and decision curve analyses found lower net benefit compared with the originals scores. Conclusions: Addition of biomarkers enhanced the predictive value of CHA(2)DS(2)-VASc and HAS-BLED, although the overall improvement was modest and the added predictive advantage over original scores was marginal.