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. NewbyNicholas L. Mills

Research output: Contribution to journalArticlepeer-review


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 (ESC) rule-out pathway, with a pathway that incorporates lower cardiac troponin concentrations to risk stratify patients.

Methods: Patients with suspected acute coronary syndrome (n=1,218) underwent high-sensitivity cardiac troponin I measurement at presentation, 3 and 6 or 12 hours. We compared the ESC pathway (<99th centile at presentation, or at 3 hours if symptoms <6 hours) with a pathway developed in the High-Sensitivity Troponin in the Evaluation of patients with Acute Coronary Syndrome (High-STEACS) study 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 (NPV) 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 pre-specified subgroups stratified by age, gender, time of symptom onset and known ischaemic heart disease.

Results: The primary outcome occurred in 15.7% (191/1,218) patients. In those <99th centile at presentation, the ESC pathway ruled out myocardial infarction in 28.1% (342/1,218) and 78.9% (961/1,218) at presentation and 3 hours respectively, missing 18 index and two 30-day events (NPV 97.9%, 95% confidence intervals [CI] 96.9-98.7%). The High-STEACS pathway ruled out 40.7% (496/1,218) and 74.2% (904/1,218) at presentation and 3 hours, missing two index and two 30-day events (NPV 99.5%, 95% CI 99.0-99.9%; P<0.001 for comparison). The NPV of the High-STEACS pathway was greater than the ESC pathway overall (P<0.001), and in all subgroups including those presenting early or known to have ischaemic 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: Unique Identifier: NCT:01852123.

Original languageEnglish
Pages (from-to)1586-1596
Number of pages11
Issue number17
Early online date29 Dec 2016
Publication statusPublished - 25 Apr 2017


  • acute coronary syndrome
  • biomarkers
  • myocardial infarction
  • troponin


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