Comparison of the Efficacy and Safety of Early Rule-Out Pathways for Acute Myocardial Infarction

Andrew R Chapman, Atul Anand, Jasper Boeddinghaus, Amy V Ferry, Dennis Sandeman, Philip D Adamson, Jack Andrews, Stephanie Tan, Sheun F Cheng, Michelle D'Souza, Kate Orme, Fiona E Strachan, Thomas Nestelberger, Raphael Twerenbold, Patrick Badertscher, Tobias Reichlin, Alasdair Gray, Anoop S V Shah, Christian Mueller, David E Newby, Nicholas L Mills, Andrew R Chapman, Atul Anand, Jasper Boeddinghaus, Amy V Ferry, Dennis Sandeman, Philip D Adamson, Jack Andrews, Stephanie Tan, Sheun F Cheng, Michelle D'Souza, Kate Orme, Fiona E Strachan, Thomas Nestelberger, Raphael Twerenbold, Patrick Badertscher, Tobias Reichlin, Alasdair Gray, Anoop S V Shah, Christian Mueller, David E Newby, Nicholas L Mills

Abstract

Background: High-sensitivity cardiac troponin assays enable myocardial infarction to be ruled out earlier, but the optimal approach is uncertain. We compared the European Society of Cardiology rule-out pathway with a pathway that incorporates lower cardiac troponin concentrations to risk stratify patients.

Methods: Patients with suspected acute coronary syndrome (n=1218) underwent high-sensitivity cardiac troponin I measurement at presentation and 3 and 6 or 12 hours. We compared the European Society of Cardiology pathway (<99th centile at presentation or at 3 hours if symptoms <6 hours) with a pathway developed in the High-STEACS study (High-Sensitivity Troponin in the Evaluation of Patients With Acute Coronary Syndrome) population (<5 ng/L at presentation or change <3 ng/L and <99th centile at 3 hours). The primary outcome was a comparison of the negative predictive value of both pathways for index type 1 myocardial infarction or type 1 myocardial infarction or cardiac death at 30 days. We evaluated the primary outcome in prespecified subgroups stratified by age, sex, time of symptom onset, and known ischemic heart disease.

Results: The primary outcome occurred in 15.7% (191 of 1218) patients. In those less than the 99th centile at presentation, the European Society of Cardiology pathway ruled out myocardial infarction in 28.1% (342 of 1218) and 78.9% (961 of 1218) at presentation and 3 hours, respectively, missing 18 index and two 30-day events (negative predictive value, 97.9%; 95% confidence interval, 96.9-98.7). The High-STEACS pathway ruled out 40.7% (496 of 1218) and 74.2% (904 of 1218) at presentation and 3 hours, missing 2 index and two 30-day events (negative predictive value, 99.5%; 95% confidence interval, 99.0-99.9; P<0.001 for comparison). The negative predictive value of the High-STEACS pathway was greater than the European Society of Cardiology pathway overall (P<0.001) and in all subgroups, including those presenting early or known to have ischemic heart disease.

Conclusions: Use of the High-STEACS pathway incorporating low high-sensitivity cardiac troponin concentrations rules out myocardial infarction in more patients at presentation and misses 5-fold fewer index myocardial infarctions than guideline-approved pathways based exclusively on the 99th centile.

Clinical trial registration: URL: https://ichgcp.net/clinical-trials-registry/NCT01852123" title="See in ClinicalTrials.gov">NCT01852123.

Keywords: acute coronary syndrome; biomarkers; myocardial infarction; troponin.

© 2016 The Authors.

Figures

Figure 1.
Figure 1.
Summary of the European Society of Cardiology (ESC; A) and High-STEACS (High-Sensitivity Troponin in the Evaluation of Patients With Acute Coronary Syndrome; B) rule-out pathways for myocardial infarction. Percentages indicate number of patients ruled in or out at a given time point as a proportion of the analysis population (n=1218). *In the High-STEACS pathway, patients with cardiac troponin concentrations <5 ng/L who present within 2 hours of symptom onset are retested at 3 hours. hs-cTnI indicates high-sensitivity cardiac troponin I (www.highsteacs.com).
Figure 2.
Figure 2.
Negative predictive value (NPV) for index type 1 myocardial infarction or for myocardial infarction or cardiac death at 30 days of conventional and High-STEACS (High-Sensitivity Troponin in the Evaluation of Patients With Acute Coronary Syndrome) pathways. Forest plot of the NPV and 95% confidence intervals (CIs) of the High-STEACS pathway (red) and the European Society of Cardiology (ESC) pathway (blue) stratified by prespecified subgroups. Numbers are true negative (TN), false negative (FN), and NPV (95% CIs). The vertical dashed line (red) highlights the central estimate of the NPV of the High-STEACS pathway in the total population.

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