An analysis of a randomized trial found that a cardiovascular biomarker score may help predict the risk for stroke, systemic embolic events and death in patients with atrial fibrillation.
The biomarkers were cardiac troponin I, N-terminal pro-B-type natriuretic peptide and D-dimer levels
Lead researcher Christian T. Ruff, MD, of Brigham and Women’s Hospital and Harvard Medical School in Boston, and colleagues published their results online in JAMA Cardiology on Oct. 5.
The researchers evaluated data on 4,880 patients from the randomized, double-blind, double-dummy ENGAGE AF-TIMI 48 trial, which compared two, once-daily edoxaban (Savaysa) dose regimens with warfarin. Daiichi Sankyo, which manufactures edoxaban, funded the trial. The FDA approved edoxaban in January 2015 to reduce the risk of stroke and systemic embolism in patients with non-valvular atrial fibrillation.
This prespecified subanalysis included the patients who had all three biomarkers available at randomization. All of the patients had atrial fibrillation and a CHADS2 risk score of 2 or higher. The median age was 71 years old, and 37.3 percent of the patients were women.
The researchers mentioned that physicians typically use the CHA2DS2-VASc score to identify patients’ risk of thromboembolism and whether they will benefit from anticoagulant therapy.
After the researchers adjusted for the CHA2DS2-VASc score, there was a statistically significant 2.8-fold to 4.2-fold gradient of risk of stroke, systemic embolic event or death when they compared the highest and lowest concentrations for each of the biomarkers. There was also a 1.6-fold to 3.9 fold gradient for stroke and systemic embolic event alone.
Based on a multimarker risk score that the researchers developed, the rate of stroke, systemic embolic event or death ranged from 1.2 percent per year in patients with a biomarker score of 0 to 21.1 percent per year in patients with a biomarker score of 10 to 11. When using the CHA2DS2-VASc score, the rate ranged from 2.2 percent in patients with a CHA2DS2-VASc score of 2 to 9.9 percent per year in patients with a CHA2DS2-VASc score of 8 to 9.
Thus, the researchers noted that the biomarker score identified more than a 15-fold gradient of risk after adjusting for the CHA2 DS2 - VASc score as well as a 7-fold gradient of risk for stroke and systolic embolic event alone after adjusting for the CHA2DS2-VASc score.
“Our data support the concept that biomarkers may contribute significant additional information regarding risk that could affect management,” the researchers wrote. “Across each CHA2DS2-VASc stratum, the multimarker score consistently identified a 4-fold to 6-fold gradient of risk regardless of whether patients had a CHA2DS2-VASc score of 2 or 8.”
The researchers acknowledged a few limitations of the study. For instance, patients in the trial received anticoagulation, but the researchers developed clinical risk stratification scores in patients who did not receive anticoagulation. They also mentioned that the CHA2DS2-VASc score predicts thromboembolic events, whereas the researchers also included mortality in their endpoint. In addition, they noted that the multimarker score is still a prototype and will undergo further refinement.
“Use of the multimarker risk score significantly enhanced prognostic accuracy and reclassification,” the researchers wrote. “Incorporation of biomarkers into clinical decision making to define therapeutic management in atrial fibrillation warrants consideration.”