Clinical trial NCT03819894: Hs-cTn - Optimizing the Diagnosis of Acute Myocardial Infarction/Injury in Women
Official title: Hs-cTn - Optimizing the Diagnosis of Acute Myocardial Infarction/Injury in Women
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Myocardial Infarction
Sex Differences
High Sensitivity Troponin
Keywords: myocardial infarction
sex differences
high-sensitivity cardiac troponin
biomarkers
heart attack
emergency department
acute coronary syndrome
Lead sponsor: BC Centre for Improved Cardiovascular Health
Sponsor class: OTHER
Collaborators: name: Canadian Institutes of Health Research (CIHR)
First posted: 2019-01-29
Enrollment: 24000
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Stepped-wedge cluster-randomized trial. Unidirectional crossover design where clusters cross over sequentially, in random order, from the control to intervention phase.
Primary purpose: HEALTH_SERVICES_RESEARCH

Brief summary: The project is focussed on evaluating the impact of using a female-specific threshold in the diagnosis of myocardial infarction. This female threshold is lower than the overall hs-cTn threshold currently in use. The investigators hypothesize that this change in process, applied at the hospital level, will lead to better assessment, treatment and outcomes of women presenting to the emergency department with chest pain that is cardiac in nature.

Detailed description: In subjects with suspected acute coronary syndromes (ACS), females are significantly less likely to undergo investigations, receive evidence-based treatments, and consistently have worse outcomes than males. The gap in outcomes is particularly marked among adults \< 55 years of age. Sex differences in symptom presentation and in the diagnostic threshold for cardiac biomarkers have been suggested as reasons for the under-diagnosis and under-treatment of women. Cardiac troponin (cTn) T and I are proteins specific to the myocardium, which with elevated and changing concentrations detected in the blood, along with signs or symptoms consistent with myocardial ischemia, are indicative of a diagnosis of myocardial infarction (MI). With the introduction of high-sensitivity (hs) cTn tests, which allow the detection of very low concentrations of troponin, it has become evident that the level of cTn in a healthy population is approximately two-fold higher in males than in females.

Consequently, the 99th percentile threshold for cTn, the reference value used in diagnosis of MI, is lower in females compared to males. Despite this evidence and recent guidelines recommending the use of sex specific thresholds, a single, overall cTn threshold is still being used for diagnosis of MI, in both men and women, in most clinical settings.

There is mounting evidence from several jurisdictions that the rate of MI is increasing among younger females, and that there is a persistent under-diagnosis, under-treatment, and high risk of adverse outcomes among females, especially younger females, compared to their male counterparts. A better approach to the diagnostic assessment of females presenting to the emergency department (ED) with chest pain is therefore urgently needed. Additionally, several Canadian hospitals have recently made the transition from sensitive to high sensitivity cTn assays, allowing for the examination of subtle but important sex-specific differences in cTn concentrations. With this background, the investigators propose a nationwide, randomized clinical trial (RCT) to determine whether establishing female thresholds results in improved diagnosis and treatment of MI and therefore improved prognosis in women.

To determine whether the use of female hs-cTn thresholds in the assessment of women presenting to the ED with chest pain suggestive of cardiac ischemia, improves diagnostic assessment, treatment and 2-year outcomes. Specifically, the investigators will examine the impact of using female hs-cTn thresholds on:

* Diagnostic and therapeutic strategies;
* Prognosis: 2-year all-cause mortality, non-fatal MI, incident heart failure (HF) hospitalization or emergent/urgent coronary revascularization;
* Costs of diagnostic testing and treatment.

Eligibility criteria: Inclusion Criteria:

* \>20 years of age
* Present to the ED with chest pain or shortness of breath suggestive of ischemia
* Have a valid personal health identifier
* Have 1 hs-cTn test result

Exclusion Criteria:

* Have ST elevation myocardial infarction (STEMI)
* Not residents in the same province as the hospital ED to which they present or move out of province within a year

Primary outcomes:
measure: Number of patients with all-cause mortality, non-fatal myocardial infarction, hospitalization for incident heart failure, or urgent/emergent coronary revascularization (percutaneous coronary intervention or coronary artery bypass surgery)
timeFrame: 2-year post index emergency department presentation
Secondary outcomes:
measure: Number of patients with a) Non-fatal myocardial infarction or all-cause mortality; b) Urgent/emergent coronary revascularization or all-cause mortality; c) Hospitalization for heart failure or all-cause mortality.
timeFrame: 2-year post index emergency department presentation
measure: Proportion of patients who fill at least one prescription for evidence-based cardiac medications
timeFrame: Within 90 days of ED visit
measure: Proportion of patients who undergo diagnostic tests
timeFrame: Within 90 days of ED visit
Other outcomes:
Locations:
city: Vancouver
country: Canada
facility: St. Paul's Hospital
state: British Columbia
Study officials:
affiliation: Medicine, Cardiology, UBC, BC Centre for Improved Cardiovascular Health
name: Karin Humphries, DSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: Zhao Y, Izadnegahdar M, Lee MK, Kavsak PA, Singer J, Scheuermeyer F, Udell JA, Robinson S, Norris CM, Lyon AW, Pilote L, Cox J, Hassan A, Rychtera A, Johnson D, Mills NL, Christenson J, Humphries KH. High-Sensitivity Cardiac Troponin-Optimizing the Diagnosis of Acute Myocardial Infarction/Injury in Women (CODE-MI): Rationale and design for a multicenter, stepped-wedge, cluster-randomized trial. Am Heart J. 2020 Nov;229:18-28. doi: 10.1016/j.ahj.2020.06.013. Epub 2020 Jun 25.