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. 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.
Keywords: Copeptin; Early diagnosis; Effectiveness; High sensitivity troponin T; Outcomes.