Abstract
ObjectivesTo derive and externally validate a copeptin-based parsimonious score to predict unfavorable outcome 3 months after an acute ischemic stroke (AIS).MethodsThe derivation cohort consisted of patients with AIS enrolled prospectively at the University Hospital Basel, Switzerland. The validation cohort was prospectively enrolled after the derivation cohort at the University Hospital of Bern and University Hospital Basel, Switzerland, as well as Frankfurt a.M., Germany. The score components were copeptin levels, age, NIH Stroke Scale, and recanalization therapy (CoRisk score). Copeptin levels were measured in plasma drawn within 24 hours of AIS and before any recanalization therapy. The primary outcome of disability and death at 3 months was defined as modified Rankin Scale score of 3 to 6.ResultsOverall, 1,102 patients were included in the analysis; the derivation cohort contributed 319 patients, and the validation cohort contributed 783. An unfavorable outcome was observed among 436 patients (40%). For the 3-month prediction of disability and death, the CoRisk score was well calibrated in the validation cohort, for which the area under the receiver operating characteristic curve was 0.819 (95% confidence interval [CI] 0.787-0.849). The calibrated CoRisk score correctly classified 75% of patients (95% CI 72-78). The net reclassification index between the calibrated CoRisk scores with and without copeptin was 46% (95% CI 32-60).ConclusionsThe biomarker-based CoRisk score for the prediction of disability and death was externally validated, was well calibrated, and performed better than the same score without copeptin.ClinicalTrials.gov identifierNCT00390962 (derivation cohort) and NCT00878813 (validation cohort).
| Originalsprache | Englisch |
|---|---|
| Zeitschrift | Neurology |
| Jahrgang | 92 |
| Ausgabenummer | 13 |
| Seiten (von - bis) | E1517-E1525 |
| ISSN | 0028-3878 |
| DOIs | |
| Publikationsstatus | Veröffentlicht - 26.03.2019 |
Fördermittel
This study was supported by an unrestricted research grant from Thermo Fisher Scientific, Thermo Scientific Biomarkers, Clinical Diagnostics, Neuendorfstr. 25; by 16,761 Hennigsdorf-Berlin (Germany); by the University of Basel, Switzerland (Wissenschaftsfond); by the Clinical Trial Units of the University of Bern (Switzerland) through the De Quervain research grant for young clinical investigators; by the Foundation of the Inselspital Bern (Switzerland); by the Foundation Pro Scientia et Arte, Bern (Switzerland); and by the Swiss National Science Foundation. G. De Marchis received an unconditional research grant for the measurement of Copeptin from BRAHMS GmbH, Hennigsdorf, Germany. In addition, Gian Marco De Marchis was or is supported by the following grants: Swiss National Science Foundation (PBBEP3_139388); Science Funds (Wissenschaftsfonds) of the University Hospital Basel and University of Basel; Bangerter-Rhyner-Stiftung; Swisslife Jubiläumsstiftung for Medical Research; Swiss Neurologic Society; Fondazione and Dr. Ettore Balli; travel honoraria from Bayer; and speaker honoraria from Medtronic and BMS/Pfizer. T. Dankowski, I. Konig, J. Fladt, F. Fluri, and H. Gensicke report no disclosures relevant to the manuscript. C. Foerch is inventor of the following patent: Use of GFAP for identification of intracerebral hemorrhage (EP1519194 A1). He received speaker honoraria from Boehringer Ingelheim. O. Findling, R. Kurmann, and U. Fischer report no disclosures relevant to the manuscript. A. Luft received consultancies from the Bayer Scientific Advisory Board, Boehringer Ingel-heim Scientific Advisory Board, Hocoma AG, and Volketswil Scientific Advisory Board and consultancy/lecture fees from AMGEN Scientific Advisory Board. D. Buhl, S. Engelter, P. Lyrer, and M. Christ-Crain report no disclosures relevant to the manuscript. M. Arnold received an unconditional research grant for the measurement of copeptin from BRAHMS GmbH, Hennigsdorf, Germany. M. Arnold reports speaker honoraria from Bayer, Boehringer Ingelheim, and Covidien; scientific advisory board honoraria from Amgen, Bayer, Boehringer Ingelheim, BMS, Pfizer, Covidien, Daichy Sankyo, and Nestlé Health Science; and research grants from the Swiss Heart Foundation and the Swiss National Science Foundation. M. Katan received an unconditional research grant for the measurement of copeptin from BRAHMS GmbH, Hennigsdorf, Germany, and received or receives funding from the Swiss National Science Foundation (PZ00P3_142422), the Spital-Pool of the University Hospital of Zurich, the Swiss Heart Foundation, and the Leducq Foundation. Go to Neurology.org/N for full disclosures.