A Systematic Review and Collaborative Meta-Analysis to Determine the Incremental Value of Copeptin for Rapid Rule-Out of Acute Myocardial Infarction

Study Questions:

What is the value of copeptin, a surrogate for arginine vasopressin, in the diagnosis of acute myocardial infarction (AMI)?


A systematic review and collaborative meta-analysis were performed for diagnosis of AMI and assessment of prognosis in patients presenting to the emergency department with chest pain. MEDLINE/PubMed, Cochrane CENTRAL, and EMBASE were searched for studies assessing copeptin in such patients. Study authors were contacted and many provided previously unpublished data. Random-effects methods were used to compare the data for copeptin, troponin, and their combination.


From the 14 included studies, there were a total of 9,244 patients. Mean age was 62 years, 64% were male, and 18.4% were ultimately diagnosed with AMI. Patients with AMI had a higher presentation copeptin level than those without AMI (22.8 vs. 8.3 pmol/L, p < 0.001). While troponin had better diagnostic accuracy than copeptin for AMI, the combination of copeptin and troponin significantly improved sensitivity (0.905 [0.888-0.921] vs. 0.686 [0.661-0.710], p < 0.001) and negative predictive value (0.97 [0.964-0.975] vs. 0.93 [0.924-0.936], p < 0.001) compared with troponin alone. Elevation in copeptin carried a similar risk of all-cause mortality to an elevation in troponin (odds ratio 5.84 vs. 6.74, respectively, p = 0.67).


The authors concluded that copeptin not only identifies patients at risk for all-cause mortality, but its addition to troponin improved sensitivity and negative likelihood ratio for diagnosis of AMI compared with troponin alone.


This systematic review and collaborative meta-analysis suggests that copeptin alone has marginal diagnostic value for assessment of AMI. However, the combination of copeptin and the initial troponin, whether conventional or high-sensitivity, led to a significant improvement in sensitivity, negative predictive value, and negative likelihood ratios. This may be important for patient care since the addition of copeptin to troponin in the emergency department may not only help providers more rapidly identify patients with AMI, but also help identify low-risk patients who could potentially be discharged home rather than wait for further troponin measurements. Given the limitations of meta-regression techniques and lack of raw patient information, the study findings should be confirmed in prospective studies.

Keywords: Myocardial Infarction, Chest Pain, Emergency Service, Hospital, Troponin, MEDLINE

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