Instant rule-out of suspected non-ST-segment elevation myocardial infarction using high-sensitivity cardiac troponin T with Copeptin versus a single low high-sensitivity cardiac troponin T: findings from a large pooled individual data analysis on 10,329 patients

• Published in: Clinical research in cardiology Vol. 110; no. 2; pp. 194 - 199
• Main Authors: Giannitsis, Evangelos, Huber, K., Hamm, C. W., Möckel, M.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-02-2021; Springer Nature B.V
• Subjects: Calcium-binding protein; Cardiology; Clinical trials; Confidence intervals; Data analysis; Heart; Heart attacks; Markers; Medicine; Medicine & Public Health; Mortality; Myocardial infarction; Original Paper; Risk groups; Secondary analysis; Segments; Strategy; Subgroups; Troponin; Troponin T; Early diagnosis; Effectiveness; High sensitivity troponin T; Outcomes; Copeptin
• ISSN: 1861-0684; 1861-0692
• DOI: 10.1007/s00392-020-01712-y

Background
Evidence is sparse and inconsistent on the role of a dual marker strategy (DMS) combining Copeptin with cardiac troponin T (cTnT) for instant rule-out of a non-ST-segment myocardial infarction (NSTEMI) when high sensitivity cardiac troponin T (hs-cTnT) is used.
Methods
Data on 10,329 patients from 5 trials were pooled to evaluate initial Copeptin in combination with hs-cTnT against a single marker strategy (SMS) based on hs-cTnT < limit of detection. Endpoints were sensitivities and negative predictive values (NPV) for rule-out of NSTEMI, 30-day all-cause mortality and rates of applicability for DMS or SMS.
Results
NPV for rule-out of NSTEMI was high, exceeding 99.0% for the lower limits of the 95% confidence intervals (99.0% vs 99.2%) for DMS and SMS, and NPV for all cause death at 30 days was similar with very low mortality after rule-out [0.07% (0.0–0.4%) vs 0.0% (0.0–1.2%),
p
 = 1.0], but applicability was 2.4-fold higher [64.6% (63.0–66.2%) vs 27.9% (26.2%—29.7%),
p
 < 0.001] with DMS than SMS. In a secondary analysis on DMS after inclusion of high risk patients, performance and applicability were similar.
Conclusion
Findings corroborate the 2015 European Society of Cardiology recommendation to use dual marker strategy for instant rule-out of NSTEMI, extending evidence to hs-cTnT. Novel data demonstrate a comparably safe and effective instant rule-out with Copeptin in combination with hs-cTnT versus a single marker strategy based on very low hs-cTnT but a more than twofold higher applicability of the dual marker strategy without the need to exclude very early presenters or other important subgroups.
Graphic abstract
Dual marker strategy using hs-cTnT at 99th percentile and Copeptin versus ESC 0-h immediate rule-out based on hs-cTnT < limit of detection