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

doi:10.1161/CIRCULATIONAHA.116.025021

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 journal › Article › peer-review

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 (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: https://clinicaltrials.gov Unique Identifier: NCT:01852123.

Original language	English
Pages (from-to)	1586-1596
Number of pages	11
Journal	Circulation
Volume	135
Issue number	17
Early online date	29 Dec 2016
DOIs	https://doi.org/10.1161/CIRCULATIONAHA.116.025021
Publication status	Published - 25 Apr 2017

Keywords / Materials (for Non-textual outputs)

acute coronary syndrome
biomarkers
myocardial infarction
troponin

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10.1161/CIRCULATIONAHA.116.025021

Chapman A Comparison of the efficacy...Accepted author manuscript, 1.93 MB

High-Sensitivity Cardiac Troponin and Coronary Heart Disease
Mills, N. (Principal Investigator)
UK-based charities
2/02/16 → 1/02/21
Project: Research
High-Sensitivity Cardiac Troponin On Presentation toRule Out Myocardial Infarction (HiSTORIC)
Mills, N. (Principal Investigator)
UK-based charities
1/07/15 → 30/09/18
Project: Research
High-Sensitivitiy cardiac troponin on presentation to rule out myocardial infarction (HiSTORIC)
Mills, N. (Principal Investigator)
UK central government bodies/local authorities, health and hospital authorities
1/04/15 → 31/03/16
Project: Research

Nicholas Mills
- nick.millsed.acuk
- Deanery of Clinical Sciences - Personal Chair of Cardiology
- Centre for Cardiovascular Science
- Edinburgh Imaging
Person: Academic: Research Active

Cite this

Chapman, A. R., Anand, A., Boeddinghaus, J., Ferry, A. V., Sandeman, D., Adamson, P. D., Andrews, J., Tan, S., Cheng, S. F., D'Souza, M., Orme, K., Strachan, F. E., Nestelberger, T., Twerenbold, R., Badertscher, P., Reichlin, T., Gray, A., Shah, A. S. V., Mueller, C., ... Mills, N. L. (2017). Comparison of the Efficacy and Safety of Early Rule Out Pathways for Acute Myocardial Infarction. Circulation, 135(17), 1586-1596. https://doi.org/10.1161/CIRCULATIONAHA.116.025021

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title = "Comparison of the Efficacy and Safety of Early Rule Out Pathways for Acute Myocardial Infarction",

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 (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: https://clinicaltrials.gov Unique Identifier: NCT:01852123.",

keywords = "acute coronary syndrome, biomarkers, myocardial infarction, troponin",

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

year = "2017",

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doi = "10.1161/CIRCULATIONAHA.116.025021",

language = "English",

volume = "135",

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journal = "Circulation",

issn = "0009-7322",

publisher = "AMER HEART ASSOC",

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Chapman, AR, Anand, A, Boeddinghaus, J, Ferry, AV, Sandeman, D, Adamson, PD, Andrews, J, Tan, S, Cheng, SF, D'Souza, M, Orme, K, Strachan, FE, Nestelberger, T, Twerenbold, R, Badertscher, P, Reichlin, T, Gray, A, Shah, ASV, Mueller, C, Newby, DE & Mills, NL 2017, 'Comparison of the Efficacy and Safety of Early Rule Out Pathways for Acute Myocardial Infarction', Circulation, vol. 135, no. 17, pp. 1586-1596. https://doi.org/10.1161/CIRCULATIONAHA.116.025021

TY - JOUR

T1 - Comparison of the Efficacy and Safety of Early Rule Out Pathways for Acute Myocardial Infarction

AU - Chapman, Andrew R.

AU - Anand, Atul

AU - Boeddinghaus, Jasper

AU - Ferry, Amy V.

AU - Sandeman, Dennis

AU - Adamson, Philip D.

AU - Andrews, Jack

AU - Tan, Stephanie

AU - Cheng, Sheun F

AU - D'Souza, Michelle

AU - Orme, Kate

AU - Strachan, Fiona E.

AU - Nestelberger, Thomas

AU - Twerenbold, Raphael

AU - Badertscher, Patrick

AU - Reichlin, Tobias

AU - Gray, Alasdair

AU - Shah, Anoop S.V.

AU - Mueller, Christian

AU - Newby, David E.

AU - Mills, Nicholas L.

PY - 2017/4/25

Y1 - 2017/4/25

N2 - 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: https://clinicaltrials.gov Unique Identifier: NCT:01852123.

AB - 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: https://clinicaltrials.gov Unique Identifier: NCT:01852123.

KW - acute coronary syndrome

KW - biomarkers

KW - myocardial infarction

KW - troponin

U2 - 10.1161/CIRCULATIONAHA.116.025021

DO - 10.1161/CIRCULATIONAHA.116.025021

M3 - Article

C2 - 28034899

SN - 0009-7322

VL - 135

SP - 1586

EP - 1596

JO - Circulation

JF - Circulation

IS - 17

ER -

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

Abstract

Keywords / Materials (for Non-textual outputs)

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Projects

High-Sensitivity Cardiac Troponin and Coronary Heart Disease

High-Sensitivity Cardiac Troponin On Presentation toRule Out Myocardial Infarction (HiSTORIC)

High-Sensitivitiy cardiac troponin on presentation to rule out myocardial infarction (HiSTORIC)

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Nicholas Mills

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