Three-Biomarker Score May Outperform Clinical Risk Tools for Atrial Fibrillation

Larry Hand

October 05, 2016

BOSTON, MA — Incorporation of three biomarkers into risk assessment for stroke, systemic embolic event (SEE), or death in patients with atrial fibrillation significantly enhances risk prediction, according to a new study[1].

Dr Christian T Ruff (TIMI Study Group, Brigham and Women's Hospital, Boston) and colleagues conducted a prespecified subanalysis of patients enrolled in the ENGAGE-AF-TIMI 48 trial, analyzing data on 4880 patients who had the three biomarkers available at randomization: cardiac troponin I, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and d-dimer.

"This study reinforces that although the clinical risk scores that we use, such as CHA2DS2-VASc, are easy and good, they can be inaccurate in predicting risk," Ruff told heartwire from Medscape. "This study shows that measuring these three biomarkers powerfully improved risk prediction."

The researchers developed a multimarker risk score by assigning tiered points for higher concentrations of the biomarkers measured at baseline.

They found, after adjustment for CHA2DS2-VASc, each biomarker to be associated with a 2.8- to 4.2-fold gradient of risk when comparing the highest vs lowest concentrations among groups of increasing concentrations (P<0.001 for all).

However, they found that the multimarker score identified a more than 15-fold gradient of risk after the same adjustment.

The results were published online October 5, 2016 in JAMA Cardiology.

"Just using these biomarkers alone significantly outperforms clinical risk schemes," Ruff told heartwire .

"The biggest change in this study from others is that we incorporated not just stroke into the risk prediction but mortality as well. That's something that hasn't been traditionally done," he explained.

"Adding these lab tests dramatically and substantially improved our ability to predict risk, and this may have improved actual treatment. Just knowing a patient's risk is only really half the story. By knowing the risk more accurately, would it change the treatment of the patient in front of me? And the answer, at least what we found, is yes," he said.

"The biomarkers are catching much more of the disease process and the pathology than simple clinical questions," he added.

The multimarker score could probably be used in atrial-fibrillation patients across the board, he said. "I will say as a caveat that this study was really a proof-of-principle study to say, 'Could we use biomarker scores or combination of biomarkers to change how we approach treatment decisions regarding anticoagulation?' These biomarkers need further validation in other studies. It's not quite ready for prime time."

He added, however, "All of these tests are available and all of these tests we used are all widely commercially available tests that are used routinely throughout hospitals throughout the country and the world. We're already using these tests in other cardiovascular diseases.

"What we're really advocating in this paper is these commonly available tests can be used in combination for atrial fibrillation. When they're used in combination they're really more powerful for predicting risk than when you use just one or two. All three of them are actually adding additional information that's not captured by either other lab tests or by the clinical risk variables that we're using routinely now," he said.

Daiichi Sankyo funded the ENGAGE-AF-TIMI trial. Ruff reported serving as a paid consultant and receiving honoraria from Daiichi Sankyo, Boehringer-Ingelheim, Bayer, and Portola. Disclosures for the coauthors are listed in the article.

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