Biomarkers May Enhance Risk Stratification in AF, Studies Show

Biomarkers, such as troponin, N-terminal-pro-BNP (NT-pro-BNP), and D-dimer, provide clinicians with very useful information when it comes to diagnosis and prognosis of coronary artery disease, heart failure, and pulmonary embolism. These tools, however, have historically had limited application when evaluating risk in patients with atrial fibrillation (AF). For these patients, the primary clinical risk predictors used are the bleeding risk tools, ie, the CHA₂DS₂-Vasc and HAS-BLED scores. However, data continue to emerge that demonstrate the utility of certain biomarkers in improving risk prediction in patients with AF who are on anticoagulation.

Two studies, one published in the Journal of the American College of Cardiology¹ in November 2013 and one published in Stroke² in March 2014, showed that high-sensitivity troponin T (hs-TnT) and NT-pro-BNP, respectively, had independent prognostic value in predicting risk of adverse events such as thromboembolism and bleeding in patients with AF.  (See earlier article on the role of biomarkers in workup of new onset AF.)

In the first and much larger study (a post-hoc analysis of the ARISTOTLE trial³), hs-TnT was measured at baseline in 14,897 patients with nonvalvular AF. There was a much higher risk of stroke or systemic embolism, cardiac death, and major bleeding in patients in the highest compared with the lowest quartile of hs-TnT. In the second study, in 1172 patients with permanent AF on oral anticoagulation with warfarin, high baseline NT-pro-BNP was independently associated with the risk of stroke, composite vascular events, and mortality.  However, there was no association with bleeding events. When added to the CHA₂DS₂-Vasc score, NT-pro-BNP did improve the ability to predict embolic events and the risk of death.

These data suggest, for the first time, that biomarkers may become important tools for adding prognostic, complementary information to clinical risk predictors in AF patients taking oral anticoagulation medication. Optimal clinically relevant cut-points for these biomarkers are yet to be determined.  How such prognostic information will affect patient management also remains to be seen. Finally, additional studies are needed to determine whether such biomarkers can also be used to risk stratify patients with AF who do not otherwise qualify for oral anticoagulation. 

For now, then, these biomarkers should not be routinely checked in clinical practice but it is likely that future iterations of AF guidelines will recommend adding these to the routine evaluation of AF patients.

References:

• Hijazi A, Wallentn Sl, Siegbahn A, et al, for the ARISTOTLE Investigators. High-sensitivity troponin T and risk stratification in patients with atrial fibrillation during treatment with apixaban or warfarin.  J Am Coll Cardiol. 2014;63:52-61. doi: 10.1016/j.jacc.2013.07.093.
• Roldán V, Vílchez JA, Manzano-Fernández S, et al. Usefulness of N-terminal pro-B-type natriuretic peptide levels for stroke risk prediction in anticoagulated patients with atrial fibrillation.  Stroke. 2014;45:696-701. doi: 10.1161/STROKEAHA.113.003338. Epub 2014 Feb 11.
• Hylek EM, Held C, Alexander JH, et al.  Major bleeding in patients with atrial fibrillation receiving apixaban or warfarin: The ARISTOTLE Trial (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation): Predictors, Characteristics, and Clinical Outcomes. J Am Coll Cardiol. 2014;63:2141-2147. doi: 10.1016/j.jacc.2014.02.549. Epub 2014 Mar 19.