Early discharge using single cardiac troponin and copeptin testing in patients with suspected acute coronary syndrome (ACS): a randomized, controlled clinical process study

Abstract

Aims: This randomized controlled trial (RCT) evaluated whether a process with single combined testing of copeptin and troponin at admission in patients with low-to-intermediate risk and suspected acute coronary syndrome (ACS) does not lead to a higher proportion of major adverse cardiac events (MACE) than the current standard process (non-inferiority design).

Methods and results: A total of 902 patients were randomly assigned to either standard care or the copeptin group where patients with negative troponin and copeptin values at admission were eligible for discharge after final clinical assessment. The proportion of MACE (death, survived sudden cardiac death, acute myocardial infarction (AMI), re-hospitalization for ACS, acute unplanned percutaneous coronary intervention, coronary artery bypass grafting, or documented life threatening arrhythmias) was assessed after 30 days. Intention to treat analysis showed a MACE proportion of 5.17% [95% confidence intervals (CI) 3.30-7.65%; 23/445] in the standard group and 5.19% (95% CI 3.32-7.69%; 23/443) in the copeptin group. In the per protocol analysis, the MACE proportion was 5.34% (95% CI 3.38-7.97%) in the standard group, and 3.01% (95% CI 1.51-5.33%) in the copeptin group. These results were also corroborated by sensitivity analyses. In the copeptin group, discharged copeptin negative patients had an event rate of 0.6% (2/362).

Conclusion: After clinical work-up and single combined testing of troponin and copeptin to rule-out AMI, early discharge of low- to intermediate risk patients with suspected ACS seems to be safe and has the potential to shorten length of stay in the ED. However, our results need to be confirmed in larger clinical trials or registries, before a clinical directive can be propagated.

Keywords: Acute coronary syndrome (ACS); Acute myocardial infarction (AMI); Copeptin; Randomized controlled trial (RCT); Rule-out.

Figure 1

Consort flow diagram. A total of 13 patients were excluded from the study (6 patients withdrew, of 3 patients in the copeptin group, copeptin values were not available, 2 patients were troponin positive at admission, 1 patient had a ST-elevation myocardial infarction at admission, 1 patient had been randomized previously). In 72 copeptin-negative patients in the copeptin group, the treating physician decided that discharge was not possible, 71 of them were admitted to the chest pain units, 1 refused to be admitted. A total of 14 patients (1.6%) were lost to follow-up (FU) at 30 days and not considered in the complete case analysis, 8 in the copeptin and 6 in the standard group, the in-hospital FU was available for all patients. *n = 1 randomized 12 h after admission; n = 1 suspected aortic dissection at admission; **n = 5 patients were lost to 30d-FU but included in the complete case analysis (ITT). Of those n = 4 had an in-hospital major cardiac events (MACE), one patient did not have an initial event but his death date was identified in the German central registry.

Figure 2

Major adverse cardiac events (MACE) proportions in study groups and in copeptin subgroups. Patients were randomized into copeptin and standard group, where MACE proportions were very similar. Copeptin results were only revealed to the treating staff in the copeptin group. In subgroups of copeptin-positive and copeptin-negative patients, major adverse cardiac event (MACE) rates are higher in copeptin positives. MACE proportions are lowest in discharged copeptin-negative patients.

Figure 3

Forest plot for differences in major adverse cardiac event (MACE) proportions. Absolute differences in MACE proportions within 30 days between the study groups with one-sided 97.5% CIs. The non-inferiority margin was prospectively defined at 5%. In none of the performed analyses, the non-inferiority margin was exceeded.