ARTICLE IN BRIEF
Investigators reported that elevated concentrations of amino terminal pro–B-type natriuretic peptide may identify a subgroup of ischemic stroke patients without known atrial fibrillation who may benefit more from anticoagulants in preventing secondary stroke.
Many studies have shown that there is no difference in prescribing warfarin over aspirin in stroke patients to prevent a subsequent vascular attack, unless there is clear evidence of atrial fibrillation. But what if there was an underlying cardiac cause that triggered the stroke that was not evident on traditional tests?
Mitchell Elkind, MD, and his colleagues at Columbia University, decided to test this possibility by looking at a peptide — amino terminal pro–B-type natriuretic peptide (NT-proBNP). Elevated markers of this peptide are associated with atrial fibrillation and heart failure. They set out to measure NT-proBNP in stored serum collected from newly diagnosed stroke patients who were enrolled in the Antiphospholipid Antibodies and Stroke Study (APASS) and the Warfarin-Aspirin Recurrent Stroke Study (WARSS). If they had unrecognized atrial fibrillation, they would benefit from an anticoagulant over an antiplatelet, said Dr. Elkind.
Dr. Elkind and colleagues thought that NT-proBNP would identify a subgroup of patients in whom relative efficacy of warfarin and aspirin would be modified by NT-proBNP concentrations. They looked to the NT-proBNP concentrations to see whether the biomarker could predict whether warfarin or aspirin prevented recurrent ischemic stroke or death two years after the initial incident. They found that that for about 5 percent of participants, high concentrations of the peptide seemed to confer a benefit from warfarin in preventing recurrent stroke. The results of the study, which were published in the March issue of the journal Stroke, were reported at the AAN annual meeting in San Diego in March.
About 95 percent of 1,028 patients with assays from stored serum had NT-proBNP less than 750 pg/mL, and among them, no evidence for treatment effect modification was apparent, said Dr. Elkind. But for 49 patients with NT-proBNP greater than 750 pg/mL, the two-year rate of events per 100 person-years was 45.9 for the aspirin group and 16.6 for the warfarin group; while for 979 patients with NT-proBNP less than 750 pg/mL, rates were similar for both treatments. For those with NT-proBNP greater than 750 pg/mL, the hazard ratio was 0.31 (95% confidence interval 0.12-0.84, p = 0.021) significantly favoring warfarin over aspirin. A formal test for interaction of NT-proBNP with treatment was significant (p = 0.01).
What it means, he said, is that there was a benefit for those on warfarin if they had very high levels of the marker. The high levels of NT-proBNP meant that they had unrecognized atrial fibrillation or they were at high risk of developing atrial fibrillation. About 5 percent of the study participants had high concentrations of the peptide without any other signs of atrial fibrillation or heart failure.
“It is too early for us to say that neurologists should measure NT-proBNP concentrations, but future studies may want to look for elevations of the peptide to validate our findings,” said Dr. Elkind.
For secondary stroke prevention, Dr. Elkind said elevated NT-proBNP concentrations may identify a subgroup of ischemic stroke patients without known atrial fibrillation, about 5 percent in this study, who may benefit more from anticoagulants.
“It's an exciting finding,” said Dr. Elkind. “We do think there is something there, but more studies are needed to see how this would influence treatment.”
“This subgroup analysis from the WARSS trial is intriguing regarding potential stroke cases who may have an under-recognized cardiac source,” said Ralph L. Sacco, MD, a professor and Olemberg chair of neurology at the McKnight Brain Institute of the Miller School of Medicine at University of Miami, and chief of neurology at the Jackson Memorial Hospital. Dr. Sacco was a co-investigator in the APASS-WARSS study, but was not involved in this sub-study.
“We know that there are still too many stroke cases that are labeled infarcts of undetermined cause, and some of these may have unrecognized cardiac sources that have not yet been diagnosed,” he said. “This biomarker may help identify stroke patients who could have a cardiac source of embolism, but it would be premature to make any treatment recommendations without further studies.”
For additional commentary on the study, watch the accompanying video with Neurology Today Editor-in-Chief Steven P. Ringel, MD, and Associate Editor Robert Holloway, MD.
TUNE IN: Can a biomarker predict which ischemic stroke patients benefit from anticoagulants or antiplatelet agents? In a video interview, Neurology Today's Editor-in-Chief Steven P. Ringel, MD, and Associate Editor Robert Holloway, MD, discuss the key clinical takeaways from the latest analysis of data from the Antiphospholipid Antibodies and Stroke Study and the Warfarin-Aspirin Recurrent Stroke Study: http://bit.ly/aNQ4KB.
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•. Longstreth WT Jr, Kronmal RA, deFilippi CR, et al. Amino terminal pro-B-type natriuretic peptide, secondary stroke prevention, and choice of antithrombotic therapy. Stroke 2013;44(3):714–719; E-pub 2013 Jan. 22.