Hs-cTn - Optimizing the Diagnosis of Acute Myocardial Infarction/Injury in Women (CODE-MI)

BC Centre for Improved Cardiovascular Health

Status: Active, not recruiting

Conditions: Sex Differences; High Sensitivity Troponin; Myocardial Infarction

Treatments: Diagnostic Test: Introduction of a lower female hs-cTn threshold

Study type: Interventional

Funder types: Other

Identifiers

NCT03819894

H18-02116

Details and patient eligibility

About

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.

Full 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.

Enrollment: 24,000 estimated patients

Sex: All

Ages: 20+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Health Services Research

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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24,000 participants in 2 patient groups

Intervention

Experimental group

Description:

The intervention is the introduction of a lower female threshold. In cluster-randomized trials, the cluster (i.e., hospital) is the unit of randomization.

Treatment:

Diagnostic Test: Introduction of a lower female hs-cTn threshold

Control

No Intervention group

Description:

The control phase will be standard of care, with the use of an overall population hs-cTn T and I threshold, for both men and women, to identify those with myocardial injury/infarction.