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CLINICAL RESEARCH: BIOMARKERS

Incremental Value of Copeptin for Rapid Rule Out of Acute Myocardial Infarction

Tobias Reichlin, MD^_*, Willibald Hochholzer, MD^_*, Claudia Stelzig, MSc^_*, Kirsten Laule, MSc^_*, Heike Freidank, MD, Nils G. Morgenthaler, MD, Andreas Bergmann, PhD, Mihael Potocki, MD^_*, Markus Noveanu, MD^_*, Tobias Breidthardt, MD^_*, Andreas Christ, MD^_*, Tujana Boldanova, MD^_*, Ramona Merki, MD^_*, Nora Schaub, MD^_*, Roland Bingisser, MD^_*, Michael Christ, MD^_* and Christian Mueller, MD^_*,_*

^_* Department of Internal Medicine, University Hospital, Basel, Switzerland
Department of Laboratory Medicine, University Hospital, Basel, Switzerland
Research Department, Brahms AG, Henningsdorf, Germany

Manuscript received January 4, 2009; accepted January 28, 2009.

^_* Reprint requests and correspondence: Prof. Dr. Christian Mueller, Department of Internal Medicine, University Hospital Basel, Petersgraben 4, Basel CH-4031, Switzerland (Email: chmueller{at}uhbs.ch).

Objectives: The purpose of this study was to examine the incremental value of copeptin for rapid rule out of acute myocardial infarction (AMI).

Background: The rapid and reliable exclusion of AMI is a major unmet clinical need. Copeptin, the C-terminal part of the vasopressin prohormone, as a marker of acute endogenous stress may be useful in this setting.

Methods: In 487 consecutive patients presenting to the emergency department with symptoms suggestive of AMI, we measured levels of copeptin at presentation, using a novel sandwich immunoluminometric assay in a blinded fashion. The final diagnosis was adjudicated by 2 independent cardiologists using all available data.

Results: The adjudicated final diagnosis was AMI in 81 patients (17%). Copeptin levels were significantly higher in AMI patients compared with those in patients having other diagnoses (median 20.8 pmol/l vs. 6.0 pmol/l, p < 0.001). The combination of troponin T and copeptin at initial presentation resulted in an area under the receiver-operating characteristic curve of 0.97 (95% confidence interval: 0.95 to 0.98), which was significantly higher than the 0.86 (95% confidence interval: 0.80 to 0.92) for troponin T alone (p < 0.001). A copeptin level <14 pmol/l in combination with a troponin T 0.01 µg/l correctly ruled out AMI with a sensitivity of 98.8% and a negative predictive value of 99.7%.

Conclusions: The additional use of copeptin seems to allow a rapid and reliable rule out of AMI already at presentation and may thereby obviate the need for prolonged monitoring and serial blood sampling in the majority of patients. (Advantageous Predictors of Acute Coronary Syndromes Evaluation [APACE]; NCT00470587 [ClinicalTrials.gov] )

Key Words: copeptin • rule out • acute myocardial infarction • troponin

Abbreviations and Acronyms   AMI = acute myocardial infarction   AUC = area under the curve   CI = confidence interval   ECG = electrocardiography   ED = emergency department   ROC = receiver-operator characteristic

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J. Am. Coll. Cardiol. 2009 54: A22. [Full Text] [PDF]