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

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Multiple studies have evaluated copeptin, a surrogate for arginine vasopressin, in the diagnosis of acute myocardial infarction (AMI) with mixed results. 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 Study investigators were contacted, and many provided previously unpublished data. Random-effects methods were used to compare the data for copeptin, troponin, and their combination. There were a total of 9,244 patients from the 14 included studies. Mean age was 62 years; 64% were men; 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, respectively, p <0.001). Although troponin had better diagnostic accuracy than copeptin for AMI, the combination of copeptin and troponin significantly improved the sensitivity (0.905 [0.888 to 0.921] vs 0.686 [0.661 to 0.710], respectively, p <0.001) and negative predictive value (0.97 [0.964 to 0.975] vs 0.93 [0.924 to 0.936], respectively, 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). In conclusion, copeptin not only identifies patients at risk of all-cause mortality, but its addition to troponin improved the sensitivity and negative likelihood ratio for diagnosis of AMI compared with troponin alone. Thus, copeptin may help identify patients who may be safely discharged early from the emergency department.

Section snippets

Methods

Prespecified inclusion and exclusion criteria were established at the outset of the study. We included any study that (1) assessed patients who presented to the emergency department with nontraumatic chest pain and (2) measured copeptin levels. We excluded any study that (1) limited patients to those only with myocardial infarction or a specific subgroup of patients, (2) excluded patients with an initial positive troponin, and (3) utilized a case-control format. We included studies regardless

Results

Of 322 citations on copeptin, we assessed 66 abstracts from which we performed detailed review of 35 full-text manuscripts. We excluded 31 abstracts because they pertained to heart failure, pulmonary embolus, or other disease states that cause chest pain but do not meet criteria for enrollment in our study. AMI was not the outcome of interest for the study. After evaluation based on prespecified inclusion and exclusion criteria, 22 articles were excluded because of the performance of the study

Discussion

The findings of this systematic review and collaborative meta-analysis demonstrate that copeptin alone has marginal diagnostic value for the assessment of AMI. However, the combination of copeptin and the initial troponin, whether conventional or high sensitivity, led to a significant improvement in sensitivity, NPV, and negative likelihood ratios. This is important for patient care because the addition of copeptin to troponin in the emergency department may not only help providers more rapidly

Disclosures

Dr. Epstein – equity holder in and consultant for GenWay Biotech, Dr. Miró – grant support from Brahms Thermofisher, Catalonian and Spanish government, consultant for Novartis, lecturer for Bayer, Dr. Giannitsis – research support from Roche Diagnostics, AstraZeneca, Mitsubishi Chemicals, Siemens Healthcare, Brahms Thermofisher consultant for Roche Diagnostics, AstraZeneca, Bayer Schering, and Brahms Thermofisher, honoraria from Roche Diagnostics, AstraZeneca, Siemens Healthcare, Mitsubishi

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