Biomarkers-in-Cardiology 8 RE-VISITED-Consistent Safety of Early Discharge with a Dual Marker Strategy Combining a Normal hs-cTnT with a Normal Copeptin in Low-to-Intermediate Risk Patients with Suspected Acute Coronary Syndrome-A Secondary Analysis of the Randomized Biomarkers-in-Cardiology 8 Trial.

Evangelos Giannitsis,Hugo A Katus,Anna Slagman,Tania Garfias-Veitl,Stephan Von Haehling,Kurt Huber,Julia Searle,Martin Möckel,Christian Müller,Christian W Hamm,Stefan Blankenberg,Jörn O Vollert

doi:10.3390/cells11020211

Abstract

Regarding the management of suspected Non-ST-segment-elevation acute coronary syndrome (ACS), the main Biomarker-in-Cardiology (BIC)-8 randomized controlled trial study had reported non-inferiority for the incidence of major adverse cardiac events at 30 days in the Copeptin group (dual marker strategy of copeptin and hs-cTnT at presentation) compared to the standard process (serial hs-cTnT testing). However, in 349 (38.7%) of the 902 patients, high-sensitivity cardiac troponin was not available for the treating physicians. High sensitivity cardiac troponin T was re-measured from thawed blood samples collected at baseline. This cohort qualified for a re-analysis of the 30-day incidence rate of MACE (death, survived cardiac death, acute myocardial infarction, re-hospitalization for acute coronary syndrome, acute unplanned percutaneous coronary intervention, coronary bypass grafting, or documented life-threatening arrhythmias), or components of the primary endpoint including death or death/MI. After re-measurement of troponin and exclusion of 9 patients with insufficient blood sample volume, 893 patients qualified for re-analysis. A total of 57 cases were detected with high sensitivity cardiac troponin T ≥ 14 ng/L who had been classified as “troponin negative” based on a conventional cardiac troponin T or I < 99th percentile upper limit of normal. Major adverse cardiac events rates after exclusion were non-inferior in the Copeptin group compared to the standard group (4.34% (95% confidence intervals 2.60–6.78%) vs. 4.27% (2.55–6.66%)). Rates were 53% lower in the per-protocol analysis (HR 0.47, 95% CI: 0.18–1.15, p = 0.09). No deaths occurred within 30 days in the discharged low risk patients of the Copeptin group. Copeptin combined with high sensitivity cardiac troponin is useful for risk stratification and allows early discharge of low-to-intermediate risk patients with suspected acute coronary syndrome is as safe as a re-testing strategy at 3 h or later.

Highlights

The 2020 ESC Guidelines on non-ST-segment elevation acute coronary syndrome (NSTE)-ACS [1] were published and endorse the use of high sensitivity cardiac troponin assays and fast diagnostic protocols
For several debatable reasons [2], the dual marker strategy (DMS) that allows an instant rule-out of myocardial infarction (MI) when copeptin and cTn are below respective cut-offs was discouraged despite the recommendation [1] to consider copeptin whenever a high sensitivity cTn assay is not available
Patients were excluded if they were diagnosed with ST-elevation myocardial infarction (STEMI), if hospital admission was indicated due to high risk as defined in current guidelines, and if hospital admission was necessary for any other reason

Summary

Introduction

The 2020 ESC Guidelines on non-ST-segment elevation acute coronary syndrome (NSTE)-ACS [1] were published and endorse the use of high sensitivity cardiac troponin (hs-cTn) assays and fast diagnostic protocols. For several debatable reasons [2], the dual marker strategy (DMS) that allows an instant rule-out of myocardial infarction (MI) when copeptin and cTn are below respective cut-offs was discouraged despite the recommendation [1] to consider copeptin whenever a high sensitivity cTn assay is not available. The recommendation to use copeptin together with a conventional and contemporary sensitive cTn assay (cTn) has beneficial impact on the daily routine in ruling out NSTE-ACS since these assays are still used in the majority of hospitals worldwide [3]. Despite the new 2020 ESC Guidelines on NSTE-ACS [1], the vast majority of observational trials found significantly improved sensitivities and negative predictive values, even if copeptin was combined with a hs-cTn assay [4,5,6,7]. Inferior prognostic performance of DMS was observed in studies where retrospective analysis was not restricted to patients with low-to-intermediate risk [9,10]

Methods

Results

Conclusion