Copeptin for the Prediction of Recurrent Cerebrovascular Events After Transient Ischemic Attack

The risk of stroke is increased after a transient ischemic attack (TIA), but the ability to discriminate patients at high versus low stroke risk is still suboptimal. The ABCD2 score, with higher scores indicating greater stroke risk, aims at helping primary and emergency care physicians in the triage of patients with TIA. Although all patients with TIA need an immediate work-up, North-American guidelines recommend that patients with an ABCD2 score ≥3 should be hospitalized given their high risk of early stroke. Yet, a recent meta-analysis found that the ABCD2 score improved risk stratification only to a small degree. To advance the ABCD2 score, the presence of ischemic injuries on MRI and carotid stenosis has been incorporated into a new score, the ABCD3-I score. The limited availability of urgent MRI, however, prevents the ABCD3-I score from being widely used. Consequently, there is a growing interest in accurate, rapidly measurable, and affordable blood markers, which may improve the ABCD2 score, without incorporating Background and Purpose—Copeptin has been associated with recurrent cerebrovascular events after transient ischemic attack (TIA). In an independent cohort, we evaluated copeptin for the prediction of recurrent cerebrovascular events within 3 months after TIA and assessed the incremental value of copeptin compared with the ABCD2 (age, blood, clinical features of TIA, duration of symptoms, presence of diabetes mellitus) and ABCD3-I (ABCD2, dual TIA [the presence of ≥2 TIA symptoms within 7 days], imaging [the presence of abnormal findings on neuroimaging]) scores. Methods—This prospective, multicenter cohort study was conducted at 3 tertiary Stroke Centers in Switzerland and Germany. Results—From March 2009 through April 2011, we included 302 patients with TIA admitted within 24 hours from symptom onset. Of 28 patients with a recurrent cerebrovascular event within 3 months (stroke or TIA), 11 patients had a stroke. Although the association of copeptin with recurrent cerebrovascular events was not significant, the association with stroke alone as end point was significant. After adjusting for the ABCD2 score, a 10-fold increase in copeptin levels was associated with an odds ratio for stroke of 3.39 (95% confidence interval, 1.28–8.96; P=0.01). After addition of copeptin to the ABCD2 score, the area under the curve of the ABCD2 score improved from 0.60 (95% confidence interval, 0.46– 0.74) to 0.74 (95% confidence interval, 0.60–0.88, P=0.02). In patients with MRI (n=223), the area under the curve of the ABCD3-I score increased in similar magnitude, although not significantly. Based on copeptin, 31.2% of patients were correctly reclassified across the risk categories of the ABCD2 score (net reclassification improvement; P=0.17). Conclusions—Copeptin improved the prognostic value of the ABCD2 score for the prediction of stroke but not TIA, and it may help clinicians in refining risk stratification for patients with TIA. Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00878813. (Stroke. 2014;45:2918-2923.)