Objectives The goal of this study was to demonstrate that copeptin levels <14 pmol/L allow ruling out acute myocardial infarction (AMI) when used in combination with cardiac troponin I (cTnI) <99th percentile and a nondiagnostic electrocardiogram at the time of presentation to the emergency department (ED). Background Copeptin is secreted from the pituitary early in the course of AMI. Methods This was a 16-site study in 1,967 patients with chest pain presenting to an ED within 6 hours of pain onset. Baseline demographic characteristics and clinical data were collected prospectively. Copeptin levels and a contemporary sensitive cTnI (99th percentile 40 ng/l; 10% coefficient of variation 0.03 μg/l) were measured in a core laboratory. Patients were followed up for 180 days. The primary outcome was diagnosis of AMI. Final diagnoses were adjudicated by 2 independent cardiologists blinded to copeptin results. Results AMI was the final diagnosis in 156 patients (7.9%). A negative copeptin and cTnI at baseline ruled out AMI for 58% of patients, with a negative predictive value of 99.2% (95% confidence interval: 98.5 to 99.6). AMIs not detected by the initial cTnI alone were picked up with copeptin >14 pmol/l in 23 (72%) of 32 patients. Non-ST-segment elevation myocardial infarctions undetected by cTnI at 0 h were detected with copeptin >14 pmol/l in 10 (53%) of 19 patients. Projected average time-to-decision could be reduced by 43% (from 3.0 h to 1.8 h) by the early rule out of 58% of patients. Both abnormal copeptin and cTnI were predictors of death at 180 days (p < 0.0001 for both; c index 0.784 and 0.800, respectively). Both were independent of age and each other and provided additional predictive value (all p < 0.0001). Conclusions Adding copeptin to cTnI allowed safe rule out of AMI with a negative predictive value >99% in patients presenting with suspected acute coronary syndromes. This combination has the potential to rule out AMI in 58% of patients without serial blood draws. (Investigation of the Biomarker Copeptin in Patients With Acute Myocardial Infarction [NCT00952744]).
Bibliographical noteFunding Information:
Dr. Maisel reports consulting honoraria from Alere, BG Medicine, and Critical Diagnostics; he reports research or speaking honoraria from BG Medicine, Abbott Laboratories, Alere, and Siemens Healthcare. Dr. Mueller has received research support from Abbott Laboratories, Alere, Beckman Coulter, BRAHMS, Critical Diagnostics, Nanosphere, Roche Laboratories, Siemens Healthcare, and 8sense . Dr. Mueller has received speaker honoraria from Abbott Laboratories, Alere, BRAHMS, Novartis, Roche Laboratories, and Siemens Healthcare. Dr. Neath has received consulting honoraria from Thermo Fisher Scientific, Alere, and Hycor. Dr. Christenson has relationships with Siemens Healthcare, BG Medicine, Critical Diagnostics, and Becton Dickinson. Dr. Morgenthaler was formerly an employee of BRAHMS-AG. Drs. McCord and Nowak report receiving research funding from BRAHMS . Dr. Vilke has received consulting honorarium from Janssen Pharmaceuticals. Dr. Daniels has received honoraria from Singulex, Alere, Critical Diagnostics, Thermo Fisher, and Roche Laboratories. Dr. Hollander reports research funding from Alere, Abbott Laboratories, BRAHMS, Siemens Healthcare, and Radiometer . Dr. Apple has research or consulting relationships with the following: Abbott Laboratories, Roche Laboratories, Radiometer, BRAHMS, Siemens Healthcare, Becton Dickinson, Alere/Biosite, Ortho-Clinical Diagnostics, Instrumentation Laboratories, and Beckman Coulter. Dr. Cannon reports no disclosures other than researching funding for this trial. Dr. Nagurney reports research funding from Alere, Nanosphere, and Fisher . Dr. Schreiber has received research funding from Abbott Laboratories . Dr. deFilippi reports a consulting relationship with Siemens Healthcare Diagnostics.
Dr. Hogan reports no disclosures other than research funding from the sponsor of the trial via CLINDEVOR TriMed . Dr. Diercks reports receiving institutional support from Alere, Beckman Coulter, and BRAHMS . Dr. Limkakeng has received research support from Roche Diagnostics , Abbott Laboratories , The Medicines Company , Novartis , and Portola Pharmaceuticals . Dr. Anand reports consulting, research, or speaking honoraria with the following: Novartis, Boston Scientific, Medtronic, Amgen, CVRx, Paracor, and BMS. Dr. Wu has received research grants from Roche Laboratories , Alere , and Beckman Coulter ; he has received travel support from Abbott Laboratories. Dr. Papassotiriou (deceased) was an employee of BRAHMS/Thermo Fisher. Mr. Hartman is an employee and stock option holder of Thermo Fisher Scientific. Dr. Ebmeyer is an employee of Thermo Fisher Scientific. Dr. Jaffe has received consulting relationships with Roche Laboratories, Radiometer, Abbott Laboratories, Alere, Critical Diagnostics, Ortho Diagnostics, Beckman Coulter, and Amgen. Dr. Peacock has received research grants from Abbott Laboratories , Alere , BRAHMS , Novartis , Roche Laboratories , and The Medicines Company ; consultant for Abbott Laboratories, Alere, BG, Cardiorentis, GE, Janssen, Lily, The Medicines Company, Singulex, and Verathon; member of the Speaker' Bureau for Abbott Laboratories, Alere, AstraZeneca, and Daiichi Sankyo; and ownership interest in Comprehensive Research Associates LLC, Vital Sensors, and Emergencies in Medicine LLC. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Wilson Tang, MD, served as Guest Editor for this paper.
- emergency department
- myocardial infarction
- quality improvement