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Type 2 myocardial infarction and myocardial injury: eligibility for novel medical therapy to derisk clinical trials

BACKGROUND: Patients with type 2 myocardial infarction (T2MI) and other mechanisms of nonthrombotic myocardial injury have an unmet therapeutic need. Eligibility for novel medical therapy is generally uncertain. METHODS: We predefined colchicine, eplerenone and ticagrelor as candidates for repurposi...

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Autores principales: Sykes, Robert, Briscoe, Michael, Krysztofiak, Thomas, Peck, Oliver, Mangion, Kenneth, Berry, Colin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8174491/
https://www.ncbi.nlm.nih.gov/pubmed/34083388
http://dx.doi.org/10.1136/openhrt-2021-001633
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author Sykes, Robert
Briscoe, Michael
Krysztofiak, Thomas
Peck, Oliver
Mangion, Kenneth
Berry, Colin
author_facet Sykes, Robert
Briscoe, Michael
Krysztofiak, Thomas
Peck, Oliver
Mangion, Kenneth
Berry, Colin
author_sort Sykes, Robert
collection PubMed
description BACKGROUND: Patients with type 2 myocardial infarction (T2MI) and other mechanisms of nonthrombotic myocardial injury have an unmet therapeutic need. Eligibility for novel medical therapy is generally uncertain. METHODS: We predefined colchicine, eplerenone and ticagrelor as candidates for repurposing towards novel therapy for T2MI or myocardial injury. Considering eligibility for randomisation in a clinical trial, each drug was classified according to indications and contraindications for therapy and survival for at least 24 hours following admission. Eligibility criteria for prescription were evaluated against the Summary of Medical Product Characteristics. Consecutive hospital admissions were screened to identify patients with ≥1 high-sensitivity troponin-I value >99th percentile. Endotypes of myocardial injury were adjudicated according to the Fourth Universal Definition of MI. Patients’ characteristics and medication were prospectively evaluated. RESULTS: During 1 March to 15 April 2020, 390 patients had a troponin I>URL. Reasons for exclusion: type 1 MI n=115, indeterminate diagnosis n=42, lack of capacity n=14, death <24 hours n=7, duplicates n=2. Therefore, 210 patients with T2MI/myocardial injury and 174 (82.8%) who survived to discharge were adjudicated for treatment eligibility. Patients who fulfilled eligibility criteria initially on admission and then at discharge were colchicine 25/210 (11.9%) and 23/174 (13.2%); eplerenone 57/210 (27.1%) and 45/174 (25.9%); ticagrelor 122/210 (58.1%) and 98/174 (56.3%). Forty-six (21.9%) and 38 (21.8%) patients were potentially eligible for all three drugs on admission and discharge, respectively. CONCLUSION: A reasonably high proportion of patients may be considered eligible for repurposing novel medical therapy in secondary prevention trials of type 2 MI/myocardial injury.
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spelling pubmed-81744912021-06-17 Type 2 myocardial infarction and myocardial injury: eligibility for novel medical therapy to derisk clinical trials Sykes, Robert Briscoe, Michael Krysztofiak, Thomas Peck, Oliver Mangion, Kenneth Berry, Colin Open Heart Coronary Artery Disease BACKGROUND: Patients with type 2 myocardial infarction (T2MI) and other mechanisms of nonthrombotic myocardial injury have an unmet therapeutic need. Eligibility for novel medical therapy is generally uncertain. METHODS: We predefined colchicine, eplerenone and ticagrelor as candidates for repurposing towards novel therapy for T2MI or myocardial injury. Considering eligibility for randomisation in a clinical trial, each drug was classified according to indications and contraindications for therapy and survival for at least 24 hours following admission. Eligibility criteria for prescription were evaluated against the Summary of Medical Product Characteristics. Consecutive hospital admissions were screened to identify patients with ≥1 high-sensitivity troponin-I value >99th percentile. Endotypes of myocardial injury were adjudicated according to the Fourth Universal Definition of MI. Patients’ characteristics and medication were prospectively evaluated. RESULTS: During 1 March to 15 April 2020, 390 patients had a troponin I>URL. Reasons for exclusion: type 1 MI n=115, indeterminate diagnosis n=42, lack of capacity n=14, death <24 hours n=7, duplicates n=2. Therefore, 210 patients with T2MI/myocardial injury and 174 (82.8%) who survived to discharge were adjudicated for treatment eligibility. Patients who fulfilled eligibility criteria initially on admission and then at discharge were colchicine 25/210 (11.9%) and 23/174 (13.2%); eplerenone 57/210 (27.1%) and 45/174 (25.9%); ticagrelor 122/210 (58.1%) and 98/174 (56.3%). Forty-six (21.9%) and 38 (21.8%) patients were potentially eligible for all three drugs on admission and discharge, respectively. CONCLUSION: A reasonably high proportion of patients may be considered eligible for repurposing novel medical therapy in secondary prevention trials of type 2 MI/myocardial injury. BMJ Publishing Group 2021-06-02 /pmc/articles/PMC8174491/ /pubmed/34083388 http://dx.doi.org/10.1136/openhrt-2021-001633 Text en © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) .
spellingShingle Coronary Artery Disease
Sykes, Robert
Briscoe, Michael
Krysztofiak, Thomas
Peck, Oliver
Mangion, Kenneth
Berry, Colin
Type 2 myocardial infarction and myocardial injury: eligibility for novel medical therapy to derisk clinical trials
title Type 2 myocardial infarction and myocardial injury: eligibility for novel medical therapy to derisk clinical trials
title_full Type 2 myocardial infarction and myocardial injury: eligibility for novel medical therapy to derisk clinical trials
title_fullStr Type 2 myocardial infarction and myocardial injury: eligibility for novel medical therapy to derisk clinical trials
title_full_unstemmed Type 2 myocardial infarction and myocardial injury: eligibility for novel medical therapy to derisk clinical trials
title_short Type 2 myocardial infarction and myocardial injury: eligibility for novel medical therapy to derisk clinical trials
title_sort type 2 myocardial infarction and myocardial injury: eligibility for novel medical therapy to derisk clinical trials
topic Coronary Artery Disease
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8174491/
https://www.ncbi.nlm.nih.gov/pubmed/34083388
http://dx.doi.org/10.1136/openhrt-2021-001633
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