D iagnosis of Acut e M yocardial I nfarctionInjury in Women CODEMI a multicentre steppedwedge clusterrandomized controlled trial Dr Karin Humphries and Dr Jim Christenson ID: 790624
Download The PPT/PDF document "1 hs- c Tn – O ptimizing the" is the property of its rightful owner. Permission is granted to download and print the materials on this web site for personal, non-commercial use only, and to display it on your personal computer provided you do not modify the materials and that you retain all copyright notices contained in the materials. By downloading content from our website, you accept the terms of this agreement.
Slide1
1
hs-
cTn – Optimizing the Diagnosis of Acute Myocardial Infarction/Injury in Women (CODE-MI): a multi-centre stepped-wedge cluster-randomized controlled trial
Dr. Karin Humphries and Dr. Jim Christenson
on behalf of CODE-MI Investigators
National Clinical Trial Identified Number:
NCT03819894
2
Overall Objective
To evaluate the impact of using the female-specific 99th percentile cut-point for high-sensitivity cardiac troponin (hs-cTn), compared to the overall 99th percentile cut-point, on the diagnosis, treatment and outcomes of women presenting to the emergency department with cardiac chest pain.
Slide33
Rationale for CODE-MI
Compared to men, women with acute coronary syndrome (ACS) are:
More likely
to have:
Higher risk of short- and long-term mortality, particularly among younger women
L
ess
likely
to be:
Diagnosed with myocardial infarction (MI) due to atypical symptoms and equivocal ECG findings
Referred to a cardiologist
or
to coronary angiography or revascularization
Prescribed evidence-based cardiac medications
Slide44
Rationale for Code-MI
“Significantly lower values are observed among women…..sex-specific 99th percentile URLs are recommended for hs-cTn assays.”*Failure to account for lower 99th percentile cut-point in women may contribute to the under-diagnosis of MI and poorer outcomes observed in women compared to men*Thygesen et al. Fourth Universal Definition of Myocardial Infarction. JACC Vol 72 (18), 2018URL= upper reference limit
Slide55
4
th
Universal Definition of MI
Biomarkers
ECG
Symptoms
“the term myocardial infarction should be used when there is an acute myocardial injury with clinical evidence of acute myocardial ischemia and with detection of a rise and/or fall of cardiac troponin values with at least one value above
the 99
th
percentile upper reference limit
of a healthy population”
Slide6Distribution of hs-cTn I in a healthy reference cohort
Mckie et al. Clinical Chemistry Vol 59 (7), 2013
648Female-specific cut-point < cut-point window of interest < overall cut-point
Slide77
Sex-specific
hs-cTn cut-points
Recommended sex-specific cut-points for
hs-cTn
I and T currently approved in Canada:
*Based on the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC)
** Siemens
Attellica
99
th
Percentile*
Roche
hs-cTn T
Abbott
hs-cTn
I
Beckman hs-cTn I
Siemens
hs-cTn
I**
Overall
14
26
17
46
Female-
specific
9
16
12
39
Male
- specific
16
34
20
54
Slide88
Outcomes by Cut-Point
0 60 120 180 240 300 360 Survival free from death or recurrent myocardial infarction in women with Suspected Acute Coronary Syndrome Women with no MIWomen reclassified with MI based on sex-specific hs-cTn Women with MI by single cut-pointShah et al. BMJ 2015;350
Slide9Whether implementation of female-specific hs-cTn diagnostic thresholds improves outcomes through better targeting of treatments requires urgent attention
9Call to Action
Despite this evidence and guidelines recommending sex-specific cut-points, a single, overall
cTn
cut-point is used in most clinical settings
Slide1010
Specific Objectives:
Examine the impact of using a lower female-specific hs-cTn cut-point on:Diagnostic and therapeutic strategiesPrognosis: all-cause mortality, non-fatal MI, incident heart failure (HF) hospitalization and emergent/urgent coronary revascularization at 30 days and one yearCosts of diagnostic testing and treatment
Slide1111
Design: Stepped-Wedge, Cluster-Randomized
Clusters (hospitals) cross over sequentially, in random order, from control to intervention phaseAt end of study all clusters in intervention phaseControl Phase: Standard of care, with the use of single, overall hs-cTn cut-point in both sexesIntervention Phase: Introduction of female hs-cTn cut-point
Slide12Data linkage
Data compilation from all sites
Data transfer to CIHI, Storage and AnalysisStudy Design and Timeline12
Slide1313
Novel Study Features
Hospital not patient consentEvaluation of a change in process to routine clinical practice.Patients do not undergo any research-specific procedures.No screening or patient enrolmentProcess change is applied to everyone during intervention phaseNo data collection or follow-upStudy cohort and study outcomes are obtained from routine administrative data collection
Slide1430 Sites across Canada
Slide15Ontario and Quebec
Slide1616
Study Population
Inclusion:Adults presenting to the emergency department (ED) with cardiac chest pain, with at least one hs-cTn test resultBased on CEDIS* codes 003 (chest pain, cardiac)Exclusion:< 20 years of ageInvalid personal health numberNot resident in the same province ED visit for chest pain within 1 year before current visit*Canadian Emergency Department Information System (CEDIS)ED patients with CEDIS code 004 (chest pain, non-cardiac) will also be monitored.
Slide1717
Primary Outcome
Efficacy: Composite of all-cause mortality, non-fatal MI, hospitalization for incident HF, or urgent/emergent coronary revascularization at 1-year post index ED presentation (1-year MACE). Safety:BARC Major or Life-threatening BleedingBARC =The Bleeding Academic Research Consortium
Slide1818
Main Statistical Analysis
Comparing the 1-year MACE rates between the control and intervention phases among females with peak hs-cTn within the cutpoint windowModel: mixed effects logistic regression adjusted for site variation and any secular trend
Slide1919
Sample Size Considerations
Power calculations based on following assumptions:20% 1-year MACE rate in control phaserecruitment of 116 females*per site per 6 monthstwo-sided likelihood ratio test at 0.05 α level 84% power to detect a 15% reduction in the odds of the composite endpoint during the intervention phase
Slide20Data Linkage
20
study cohort
Linkage process varies by site
The process involves linking the following data sources:
ED (NACRS) and Lab data
Discharge Abstract Database (DAD)
Provincial Prescription Database
Physician Billing
Vital Statistics
Data from all sites will be
de-identified,
stored and accessed for analysis via CIHI’s Secure Research Environment
Slide2121
hs-cTn
assay in use for at least 6 months prior to randomizationCardiology, ED and Lab leads review/approve study logistics and hospital agrees to participateEthics approval / research contract set up for paymentCompleted training using preferred modality (e.g YouTube, slide presentation, information sheets) 6-8 weeks prior to transitioning to intervention phaseIT department ready to make relevant changes to lab reporting systemSite Preparation Checklist
Slide22Study Organization:
Slide2323
CODE-MI ICVHEALTH Team
Karin Humphries
MBA, DSc, FAHA
Principal Investigator
khumphries@icvhealth.ubc.ca
Salima
Jutha
B.Sc
, CCRA
National Coordinator
CodeMI@icvhealth.ubc.ca
Yinshan
Zhao
PhD
Director of Biostatistics
yzhao@icvhealth.ubc.ca
Mona Izadnegahdar
PhD
Epidemiologist
mizadnegahdar@icvhealth.ubc.ca
@
CodeMICanada
Slide2424
Acknowledgements
Slide2525
Additional Slides
Slide26Lab
Cardiology
EDSt. Paul’s HospitalDr. Andre MattmanDr. Chris FordyceDr. Frank ScheuermeyerRoyal Jubilee/Victoria Genera HospitalDr. Gordon HoagDr. Simon RobinsonDr. Ross Hooker
Royal Columbian/ Surrey Memorial HospitalPending
British Columbia
Provincial Lead:
Dr. Frank
Scheuermeyer
Slide27Alberta
Provincial Lead:
Dr. Colleen Norris
Lab
Cardiology
ED
University of Alberta Hospital
Dr. Albert
Tsui
Dr. Michelle Graham
Dr. Bill
Sevcik
Royal Alexander Hospital
Dr. Josh
Raizman
Dr. Ben Tyrrell
Dr. Colin Peterson
Foothills Hospital
Dr. Hossein
Sadrzadeh
Dr. Bryan
Har
TBD
Slide28Lab
Cardiology
EDRoyal University HospitalDr. Andrew LyonDr. Paul BasranDr.Bruce CloadRegina General Hospital Dr. Bahera
MaliDr. Andrea Lavoie
Dr. Glenda Kaban
/
Dr. Terry Ross
Saskatchewan
Provincial Lead:
Dr. Andrew Lyon
Slide29Lab
Cardiology
EDSt. Boniface HospitalDr. Laurel ThorlaciusDr. Shelley Zieroth/ Dr. Kunal MinhasDr. Paul Ratana
Manitoba
Provincial Lead:
Dr. Shelley
Zieroth
Slide30Lab
Cardiology
EDMount Sinai HospitalDr. Barry HoffmanDr. Susanne MakDr. Bjug BorgundvaagSunnybrook HospitalDr. Mark CheungDr. Harindra
Wijeysundera
Dr. Jacques Lee
Toronto General Hospital/Toronto Western Hospital
Dr.
Vathany
Kulasingam
Dr. Jay
Udell
Dr. Steven Friedman
St. Michael’s Hospital
Dr. Daniel
Beriault
Dr.
Akshay
Bagai
/
Dr. Beth Abramson
Dr. Melissa McGowan
Kingston General Hospital
Dr. Michael Chan
Dr.
Amer
Johri
Dr. Michael Fitzpatrick
Ontario
Provincial Lead:
Dr. Jay
Udell
Slide31Lab
Cardiology
EDOttawa Hospital General SiteDr. Ron BoothDr. Michele TurekDr. Venkatesh Thiruganasambandamoorthy
Ottawa Hospital Civic Site
Dr. Christopher McCudden
Dr. Derek So
Dr.
Venkatesh
Thiruganasambandamoorthy
Hamilton General Hospital (Hamilton Health Sciences)
Dr. Peter
Kavsak
Dr. Eva
Lonn
Dr.
Andrew
Worster
Juravinski
Hospital
(Hamilton Health Sciences)
Dr. Peter
Kavsak
Dr. Eva
Lonn
Dr. Andrew
Worster
University Hospital
(London Health Sciences)
Dr.
Vipin
Bhayana
Dr. Neville
Suskin
Dr. Jonathan Dreyer
Victoria Hospital
(London Health Sciences)
Dr.
Vipin
Bhayana
Dr. Neville
Suskin
Dr. Jonathan Dreyer
Ontario - continued
Slide32Lab
Cardiology
ED Montreal General (MUHC)Dr. David BlankDr. Richard HaichinDr. Greg Clark/ Dr. Jean Marc Troquet Royal Victoria Hospital (Glen Site)Dr. David BlankDr. Richard HaichinDr. Greg Clark/ Dr. Jean Marc
Troquet
Montreal Heart Institute
Dr. Joel Lavoie
Dr. Marc
Jolicoeur
Dr. Alain
Vadeboncoeur
/
Dr. Michele Lucey
Jewish General
Dr. Elizabeth
MacNamara
Dr. Annabel Chen-
Tournoux
Dr. Marc
Afilalo
/ Dr. Eli Segal
St. Mary Hospital
Dr. Julie St-Cyr
Dr. Mathieu Walker
Dr.
Suj
Sivaraman
Quebec
Provincial Lead:
Dr. Louise
Pilote
Slide33Lab
Cardiology
ED Saint John Regional HospitalDr. Jennifer SheaDr. Sohrab LutchmedialDr. Michael Howlett/ Dr. Paul Atkinson
New Brunswick
Provincial Lead:
Dr.
Ansar
Hassan
Slide34Lab
Cardiology
ED Queen Elizabeth II HospitalDr. Amy LouDr. Ata Quraishi/Dr. Sharon MulvaghDr. Sam Campbell
Nova Scotia
Provincial Lead:
Dr.
Jafna
Cox
Slide35High-STEACS vs CODE-MI
The High-STEACS trial, published in September 2018, did not identify improved outcomes with sex-specific
hs-cTn
cut-points. However, there are important differences that support the need for CODE-MI:
Slide36Secondary Outcomes
Components of the
1-year composite outcome with death, to account for competing risk:Non-fatal MI and all-cause mortalityUrgent/emergent coronary revascularization and all-cause mortalityHospitalization for any cardiovascular indications (e.g. any HF or revascularization) and all-cause mortalityComposite of all-cause mortality, non-fatal MI, hospitalization for incident HF, or urgent/emergent coronary revascularization at 30 days post ED presentation (30-day MACE)
Slide37Secondary Outcomes
Proportion of patients who:
Fill at least one prescription for evidence-based cardiac medications (beta-blockers, ACE-I/ARB, statins, anti-platelets)Undergo diagnostic tests (nuclear medicine cardiac scan, exercise stress test, diagnostic cardiac catheterization/CT angiogram or echocardiogram) within 90 days of the ED visitLength of stay during the index admissionHealth care utilization and cost associated with:Relevant physician visits, diagnostic testing, ED visits, hospitalizations and length of stay, and cost of prescription dispensing
Slide38Planned Sub-group Analyses
1-year MACE outcome in females with CEDIS = 003 and peak
hs-cTn within the cut-point window of interest by:age: < 60 vs ≥ 60 yearsAssay: cTnT vs IChronic renal diseaseDiabetesChronic heart failure
Slide39Exploratory Analyses
Females with peak
hs-cTn outside the cut-point window of interestMale patientsPatients with CEDIS = 004STEMI Patients