Lowering the hs-cTn Threshold for Heart Attack in Women

(CODE-MI Trial)

Overseen By Salima Jutha, CCRA

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: BC Centre for Improved Cardiovascular Health

Disqualifiers: STEMI, Non-resident, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines whether using a lower threshold for a specific heart test in women can improve heart attack diagnosis. By adjusting the test, doctors aim to better identify and treat women who arrive at the emergency room with heart-related chest pain. The trial will compare this new approach to the standard method used for everyone. Women over 20 who visit the emergency room with chest pain or shortness of breath potentially related to their heart may qualify for this trial. As an unphased trial, it offers women the chance to contribute to research that could enhance the accuracy of heart attack diagnoses and treatments.

Do I need to stop my current medications to join the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that this change in process is safe for women?

Research has shown that using a lower threshold for the heart test known as high-sensitivity cardiac troponin (hs-cTn) can benefit women. One study found that women with very low levels of this marker had a 20% lower risk of death. Another study indicated that these women faced a low risk of heart attacks and deaths for up to a year. This suggests that using a lower threshold is safe and might improve health outcomes. Adopting a female-specific threshold could lead to better treatment for women with chest pain. Overall, the evidence supports that this change is well-tolerated and aids in diagnosing heart attacks more accurately for women. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it seeks to personalize heart attack diagnosis for women by introducing a lower threshold for high-sensitivity cardiac troponin (hs-cTn). Typically, the standard of care uses the same hs-cTn levels for both men and women to detect heart attacks, which might overlook some cases in women due to their naturally lower hs-cTn levels. This new approach aims to enhance diagnostic accuracy and ensure women receive timely and appropriate treatment. By potentially redefining what constitutes a heart attack in women, this trial could lead to more tailored and effective care for female patients.

What evidence suggests that introducing a lower female hs-cTn threshold is effective for diagnosing heart attacks in women?

Research has shown that using a lower threshold for the heart attack marker high-sensitivity cardiac troponin (hs-cTn) can improve diagnosis in women. Studies have found that women naturally have different hs-cTn levels than men, making a lower threshold more accurate for them. One study found a stronger connection between troponin levels and heart-related deaths in women compared to men. In this trial, the intervention arm will introduce a lower female hs-cTn threshold, which may help identify heart attacks in women that might otherwise be missed. This approach relies on clear evidence that women and men have different heart attack markers. ^{2 3 6 7 8}

Who Is on the Research Team?

Karin Humphries, DSc

Principal Investigator

Medicine, Cardiology, UBC, BC Centre for Improved Cardiovascular Health

Are You a Good Fit for This Trial?

This trial is for women over 20 who visit the emergency department with chest pain or shortness of breath that may indicate a heart issue. They must have had a high-sensitivity troponin test and live in the same province as the hospital. Women with ST elevation myocardial infarction are excluded.

Inclusion Criteria

Have a valid personal health identifier

You are 20 years old or older.

You are currently experiencing chest pain or having trouble breathing that may be related to a heart problem.

Exclusion Criteria

Not residents in the same province as the hospital ED to which they present or move out of province within a year

You have a specific type of heart attack called ST elevation myocardial infarction (STEMI).

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Control Phase

Standard of care using overall population hs-cTn T and I threshold for both men and women

Duration not specified

Intervention Phase

Introduction of a lower female threshold for hs-cTn in the diagnosis of myocardial infarction

Duration not specified

Follow-up

Participants are monitored for safety and effectiveness after treatment, including 2-year outcomes such as all-cause mortality and non-fatal myocardial infarction

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Introduction of a lower female hs-cTn threshold

Trial Overview The study tests whether using a lower threshold for troponin levels (a marker in blood) specifically for women improves diagnosis and treatment of heart attacks when they arrive at the hospital.

How Is the Trial Designed?

Group I: Intervention Experimental Treatment 1 Intervention

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

Group II: Control Active Control 1 Intervention

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.

Who Is Running the Clinical Trial?

BC Centre for Improved Cardiovascular Health

Lead Sponsor

Trials

4

Recruited

24,900+

Canadian Institutes of Health Research (CIHR)

Collaborator

Trials

1,417

Recruited

26,550,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9599969/

Prognostic Value of High-Sensitivity Cardiac Troponin in ... An overall stronger association between cardiac troponin I levels and cardiovascular death was reported for women. A subsequent analysis ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0149291824002881

Systematic Review of Sex-specific High Sensitivity Cardiac ... The data shows significantly lower 99th percentiles in females compared to 99th percentiles in males and overall. Incorporating these sex-specific 99th ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8486023/

Sex Differences in Cardiac Troponin I and T ... - PubMed Central In 19 501 (58% women, mean age 47 years) participants, the primary outcome occurred in 2.7% (306/11 375) of women and 5.1% (411/8126) of men ...

4. ahajournals.org ahajournals.org/doi/10.1161/CIRCOUTCOMES.123.010270

Safety and Effectiveness of the High-Sensitivity Cardiac ... The primary safety and effectiveness outcomes were 30-day all-cause death or myocardial infarction and 30-day hospitalizations.

5. jacc.org jacc.org/doi/10.1016/j.jacc.2018.03.515

High-Sensitivity Troponins and Outcomes After Myocardial ... During the study period, 47,133 MIs were diagnosed using cTn and 40,746 using hs-cTnT. The rate of MI increased by 5% (95% CI: 0% to 10%) after ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11287531/

Long-term prognosis of low high-sensitivity cardiac troponin T ... In a large cohort of patients with chest pain in the ED, we found an up to 20% lower risk of death in patients with undetectable hs-cTnT ...

7. jacc.org jacc.org/doi/10.1016/j.jacc.2024.04.071

Potential for Misapplication of a Uniform vs Sex-Specific ... A uniform rule-out hscTn threshold is less accurate among certain demographics, including older women and people with high cardiovascular risk.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11578548/

Single high-sensitivity troponin-I for ruling out acute coronary ... Patients with a single very low level of high-sensitivity troponin on presentation to EDs are at low risk of MI and cardiovascular death at 30 and 365 days.