TY - JOUR
T1 - High-Sensitivity Cardiac Troponin—Optimizing the Diagnosis of Acute Myocardial Infarction/Injury in Women (CODE-MI)
T2 - Rationale and design for a multicenter, stepped-wedge, cluster-randomized trial
AU - Zhao, Yinshan
AU - Izadnegahdar, Mona
AU - Lee, May K.
AU - Kavsak, Peter A.
AU - Singer, Joel
AU - Scheuermeyer, Frank
AU - Udell, Jacob A.
AU - Robinson, Simon
AU - Norris, Colleen M.
AU - Lyon, Andrew W.
AU - Pilote, Louise
AU - Cox, Jafna
AU - Hassan, Ansar
AU - Rychtera, Anni
AU - Johnson, Denise
AU - Mills, Nicholas L.
AU - Christenson, Jim
AU - Humphries, Karin H.
N1 - Funding Information:
We thank all participating hospitals; investigators; physicians; our patient partners; the CODE-MI Steering, Data Monitoring, and Education Committee members; and Salima Jutha, the national coordinator. Without their support and engagement, this study would not be possible. N. L. M. is supported by the Butler Senior Clinical Research Fellowship from the British Heart Foundation ( FS/16/14/32023 ).
Funding Information:
CODE-MI is funded by: the Canadian Institutes for Health Research and in-kind contribution and unencumbered educational support for knowledge translation activities from Roche Diagnostics International, Ltd, and Beckman Coulter, Inc.
Funding Information:
This trial is funded by the Canadian Institutes of Health Research. The funding source had no role in the design, trial conduct, analysis, or decision to publish the results. The hs-cTn manufacturers, Beckman-Coulter, Roche, and Siemens, contributed assay kits for the participating hospitals and funds to support knowledge translation. However, none of the manufacturers had any involvement in the study design, analytic plan, or knowledge translation.We thank all participating hospitals; investigators; physicians; our patient partners; the CODE-MI Steering, Data Monitoring, and Education Committee members; and Salima Jutha, the national coordinator. Without their support and engagement, this study would not be possible. N. L. M. is supported by the Butler Senior Clinical Research Fellowship from the British Heart Foundation (FS/16/14/32023). CODE-MI is funded by: the Canadian Institutes for Health Research and in-kind contribution and unencumbered educational support for knowledge translation activities from Roche Diagnostics International, Ltd, and Beckman Coulter, Inc. P. K. has received grants/reagents/consultant/advisor/ honoraria from Abbott Laboratories, Abbott Point of Care, Abbott Diagnostics Division Canada, Beckman Coulter, Ortho Clinical Diagnostics, Randox Laboratories, Roche Diagnostics, and Siemens Healthcare Diagnostics and is listed as an inventor in patents in the acute cardiovascular biomarker field filed by McMaster University. N. L. M. reports research grants from Siemens Healthineers and Abbott Diagnostics to the University of Edinburgh and honoraria from Siemens Healthineers, Abbot Diagnostics, and Roche Diagnostics. J.A.U. is supported by a Heart and Stroke Foundation National New Investigator-Ontario Clinician Scientist Award and an Ontario Ministry of Research Innovation and Science Early Researcher Award, received personal fees for consulting for or honoraria from Amgen, AstraZeneca, Boehringer-Ingelheim, Janssen, Merck, Novartis and Sanofi and reports grant support to his institutions from AstraZeneca, Novartis and Sanofi.
Publisher Copyright:
© 2020 Elsevier Inc.
PY - 2020/11
Y1 - 2020/11
N2 - Despite evidence that high-sensitivity cardiac troponin (hs-cTn) levels in women are lower than in men, a single threshold based on the 99th percentile upper reference limit of the overall reference population is commonly used to diagnose myocardial infarction in clinical practice. This trial aims to determine whether the use of a lower female-specific hs-cTn threshold would improve the diagnosis, treatment, and outcomes of women presenting to the emergency department with symptoms suggestive of myocardial ischemia. Methods/Design: CODE-MI (hs-cTn—Optimizing the Diagnosis of Acute Myocardial Infarction/Injury in Women) is a multicenter, stepped-wedge, cluster-randomized trial of 30 secondary and tertiary care hospitals across 8 Canadian provinces, with the unit of randomization being the hospital. All adults (≥20 years of age) presenting to the emergency department with symptoms suggestive of myocardial ischemia and at least 1 hs-cTn test are eligible for inclusion. Over five, 5-month intervals, hospitals will be randomized to implement lower female hs-cTn thresholds according to the assay being used at each site. Men will continue to be assessed using the overall thresholds throughout. Women with a peak hs-cTn value between the female-specific and the overall thresholds will form our primary cohort. The primary outcome, a 1-year composite of all-cause mortality or readmission for nonfatal myocardial infarction, incident heart failure, or emergent/urgent coronary revascularization, will be compared before and after the implementation of female thresholds using mixed-effects logistic regression models. The cohort and outcomes will be obtained from routinely collected administrative data. The trial is designed to detect a 20% relative risk difference in the primary outcome, or a 2.2% absolute difference, with 82% power. Conclusions: This pragmatic trial will assess whether adopting lower female hs-cTn thresholds leads to appropriate assessment of women with symptoms suggestive of myocardial infarction, thereby improving treatment and outcomes.
AB - Despite evidence that high-sensitivity cardiac troponin (hs-cTn) levels in women are lower than in men, a single threshold based on the 99th percentile upper reference limit of the overall reference population is commonly used to diagnose myocardial infarction in clinical practice. This trial aims to determine whether the use of a lower female-specific hs-cTn threshold would improve the diagnosis, treatment, and outcomes of women presenting to the emergency department with symptoms suggestive of myocardial ischemia. Methods/Design: CODE-MI (hs-cTn—Optimizing the Diagnosis of Acute Myocardial Infarction/Injury in Women) is a multicenter, stepped-wedge, cluster-randomized trial of 30 secondary and tertiary care hospitals across 8 Canadian provinces, with the unit of randomization being the hospital. All adults (≥20 years of age) presenting to the emergency department with symptoms suggestive of myocardial ischemia and at least 1 hs-cTn test are eligible for inclusion. Over five, 5-month intervals, hospitals will be randomized to implement lower female hs-cTn thresholds according to the assay being used at each site. Men will continue to be assessed using the overall thresholds throughout. Women with a peak hs-cTn value between the female-specific and the overall thresholds will form our primary cohort. The primary outcome, a 1-year composite of all-cause mortality or readmission for nonfatal myocardial infarction, incident heart failure, or emergent/urgent coronary revascularization, will be compared before and after the implementation of female thresholds using mixed-effects logistic regression models. The cohort and outcomes will be obtained from routinely collected administrative data. The trial is designed to detect a 20% relative risk difference in the primary outcome, or a 2.2% absolute difference, with 82% power. Conclusions: This pragmatic trial will assess whether adopting lower female hs-cTn thresholds leads to appropriate assessment of women with symptoms suggestive of myocardial infarction, thereby improving treatment and outcomes.
UR - http://www.scopus.com/inward/record.url?scp=85090353569&partnerID=8YFLogxK
U2 - 10.1016/j.ahj.2020.06.013
DO - 10.1016/j.ahj.2020.06.013
M3 - Article
C2 - 32916606
AN - SCOPUS:85090353569
SN - 0002-8703
VL - 229
SP - 18
EP - 28
JO - American Heart Journal
JF - American Heart Journal
ER -