Genetic Testing for Acute Coronary Syndrome

(ACCURATE Trial)

Recruiting at 1 trial location

Overseen By Navid Saleh

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: University of British Columbia

Disqualifiers: Age over 60

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Hospitalization period

250 Participants Needed

Trial Summary

What is the purpose of this trial?

ACCURATE will test the hypothesis that opportunistic genetic testing for Familial Hypercholesterolemia (FH) in patients admitted to hospital with an acute coronary syndrome will increase the diagnosis of FH and will impact patient care and outcomes. The study will recruit patients admitted to hospital with an acute coronary syndrome, and research-based genetic testing will be conducted for known FH-causing genetic variants. The results will be returned to the patients' treating physicians. The primary endpoint will be the number of patients with a new diagnosis of FH. The secondary endpoints will be the proportion of patients who undergo intensification of lipid-lowering therapy, the lowest LDL cholesterol level achieved, and the proportion of patients reaching guideline recommended lipid targets in the 12 months after the index acute coronary syndrome.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It seems likely that you can continue your current medications, especially if you are already on a statin, as the study involves genetic testing and monitoring lipid levels.

What data supports the effectiveness of genetic testing for Familial Hypercholesterolemia in treating Acute Coronary Syndrome?

Genetic testing for Familial Hypercholesterolemia (FH) helps in making a clear diagnosis, identifying individuals at higher risk for heart problems, and encouraging early and consistent treatment. This testing can also help find at-risk family members, leading to earlier treatment and better management of heart disease risk. ^{1 2 3 4 5}

Is genetic testing for familial hypercholesterolemia safe for humans?

The research does not specifically mention safety concerns related to genetic testing for familial hypercholesterolemia, suggesting it is generally considered safe for humans. ^{1 4 6 7 8}

How is genetic testing for Familial Hypercholesterolemia different from other treatments for this condition?

Genetic testing for Familial Hypercholesterolemia (FH) is unique because it helps identify individuals with a genetic predisposition to high cholesterol, allowing for early diagnosis and targeted treatment strategies. Unlike traditional treatments that focus on managing symptoms, genetic testing can guide personalized care and improve risk assessment for cardiovascular events. ^{2 3 9 10 11}

Research Team

Liam Brunham, MD PhD

Principal Investigator

University of British Columbia

Eligibility Criteria

This trial is for people under 60 who've been admitted to a cardiac unit with a heart attack (STEMI or NSTEMI) and have high cholesterol levels. It's not open to those already diagnosed with Familial Hypercholesterolemia or on certain lipid treatments.

Inclusion Criteria

I was admitted for a heart attack.

My cholesterol levels have been high in the past year.

I am younger than 60 years old.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive standard-of-care treatment or undergo genetic testing for FH during hospitalization

Hospitalization period

In-hospital stay

Follow-up

Participants are monitored for safety and effectiveness after treatment, including lipid levels and cardiovascular events

12 months

Regular follow-up visits

Treatment Details

Interventions

• Research-based genetic test for Familial Hypercholesterolemia

Trial Overview The ACCURATE study tests if genetic testing for Familial Hypercholesterolemia in patients hospitalized for acute coronary syndrome can help diagnose this condition and influence their treatment and health outcomes.

Participant Groups

Group I: Active-testing Experimental Treatment 1 Intervention

Those admitted between 6-18 months of the study meeting the inclusion criteria. Saliva samples will be collected for DNA testing.

Group II: Observation Active Control 1 Intervention

Those admitted in the first 6 months of the study that meet the inclusion criteria. Patients will be treated according to the normal standard of care for acute coronary syndrome.

Research-based genetic test for Familial Hypercholesterolemia is already approved in United States, European Union for the following indications:

Approved in United States as Genetic testing for Familial Hypercholesterolemia for:

• Diagnosis of Familial Hypercholesterolemia

Approved in European Union as Genetic testing for Familial Hypercholesterolemia for:

• Diagnosis of Familial Hypercholesterolemia

Who Is Running the Clinical Trial?

University of British Columbia

Lead Sponsor

Trials

1,506

Recruited

2,528,000+

Genome British Columbia

Industry Sponsor

Trials

13

Recruited

223,000+

Vancouver Coastal Health Research Institute

Collaborator

Trials

30

Recruited

5,600+

Findings from Research

Familial hypercholesterolemia (FH) is a common genetic disorder that is often underdiagnosed, but genetic testing can provide a definitive diagnosis and identify individuals at higher cardiovascular risk, leading to more aggressive treatment.

The Expert Consensus Panel recommends making FH genetic testing standard practice for patients with definite or probable FH and their at-risk relatives, which could improve diagnosis rates, therapy initiation, and risk assessment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Genetic Testing for Familial Hypercholesterolemia: JACC Scientific Expert Panel. Sturm, AC., Knowles, JW., Gidding, SS., et al.[2019]

The study found that the prevalence of genetically defined familial hypercholesterolemia (FH) in a hospital-based population in Taiwan is 1.13%, which is higher than previously reported rates for clinically defined FH.

Certain genetic variants, such as LDLR rs769446356 and LDLR rs730882109, significantly increase the risk of hyperlipidemia and acute myocardial infarction (AMI), highlighting the importance of genetic testing for better risk assessment and early intervention in patients with FH.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevalence of genetically defined familial hypercholesterolemia and the impact on acute myocardial infarction in Taiwanese population: A hospital-based study. Chen, YJ., Chen, IC., Chen, YM., et al.[2022]

Genetic testing has revealed that familial hypercholesterolemia (FH) affects at least 1 in 220 people in the USA, highlighting its significant prevalence and impact on public health.

Early diagnosis of FH through genetic testing could greatly reduce the risk of premature coronary artery disease, but the full benefits of such early detection have yet to be realized.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genotype-guided diagnosis in familial hypercholesterolemia: population burden and cascade screening. Hopkins, PN.[2017]

Next-generation sequencing has improved the detection of causal mutations in familial hypercholesterolemia (FH), leading to better understanding and management of the condition.

While genetic testing can enhance diagnosis and treatment strategies for FH, concerns about costs, potential discrimination, and access to therapies for those without definitive genetic results remain significant challenges.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genotype-guided diagnosis in familial hypercholesterolemia: clinical management and concerns. Hopkins, PN., Lane, SR.[2017]

Genetic testing for familial hypercholesterolemia is underutilized in Switzerland, despite guidelines recommending cascade testing from an index case to identify affected family members.

Implementing family screening with genetic testing could improve the standard of care for patients with severe hypercholesterolemia, helping to identify and manage at-risk individuals more effectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A Family History of Hypercholesterolemia - the Role of Genetics]. Podmore, C., Deillon, E., Nanchen, D.[2023]

In a study of 2938 individuals with familial hypercholesterolemia (FH), 88% were found to have pathogenic or likely pathogenic genetic variants, highlighting the importance of genetic testing for early identification and treatment of this condition.

Patients with null variants exhibited a more severe form of FH, characterized by significantly higher levels of harmful cholesterol particles, which underscores the need for tailored treatment strategies based on genetic profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mutational analysis and genotype-phenotype relation in familial hypercholesterolemia: The SAFEHEART registry. Bourbon, M., Alves, AC., Alonso, R., et al.[2018]

A study of 4563 individuals with familial hypercholesterolemia (FH) found that a limited-variant genetic screen would miss 68.9% of clinically significant pathogenic variants compared to comprehensive next-generation sequencing (NGS).

The risk of missing disease-causing variants was particularly high in individuals of Black/African American (93.7% missed) and Hispanic (84.7% missed) ancestry, highlighting the limitations of limited-variant screens in accurately identifying FH across diverse populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Limited-Variant Screening vs Comprehensive Genetic Testing for Familial Hypercholesterolemia Diagnosis. Sturm, AC., Truty, R., Callis, TE., et al.[2022]

Patient-reported outcomes (PROs) and measures (PROMs) are essential for understanding the personal experiences and concerns of patients after genetic testing for familial hypercholesterolemia (FH), which is crucial for optimizing their care.

Incorporating PROs and PROMs can help inform health systems and policy decisions regarding the utility of clinical genetic testing, ultimately leading to improved patient outcomes and tailored treatment strategies for those with FH.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Integrating Patient-Reported Outcomes Into Clinical Genetic Testing for Familial Hypercholesterolemia. Hendricks-Sturrup, RM., Block, R., Lu, CY.[2021]

In a study of 1944 Japanese patients with acute coronary syndrome (ACS), the prevalence of familial hypercholesterolemia (FH) was found to be 2.7%, indicating that FH is significantly more common in ACS patients compared to the general population.

Patients with FH were generally younger and more likely to have premature ACS, highlighting the importance of screening for FH in ACS patients, especially those with early onset of coronary artery disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevalence of familial hypercholesterolemia in patients with acute coronary syndrome in Japan: Results of the EXPLORE-J study. Harada-Shiba, M., Ako, J., Arai, H., et al.[2019]

In a study of 257 adult patients with familial hypercholesterolaemia (FH), those with genetically confirmed FH had a higher prevalence of cardiovascular events (34%) compared to those without genetic confirmation (25%), suggesting that genetic testing may help identify higher-risk patients.

However, the difference in cardiovascular risk was influenced by other factors such as age, hypertension, and body mass index, indicating that while genetic testing can be beneficial, it should be considered alongside these additional risk factors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevalence of cardiovascular events in genetically confirmed versus unconfirmed familial hypercholesterolaemia. Khan, TZ., Breen, J., Neves, E., et al.[2021]

Genetic testing is becoming essential for diagnosing familial hypercholesterolemia (FH), a genetic condition that can lead to early heart disease, with targeted next-generation sequencing (NGS) being the most effective method for accurate diagnosis.

As genetic testing for FH becomes more widespread, it is crucial to standardize how genetic variants are evaluated and to educate healthcare providers to ensure timely and appropriate treatment for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent advances in genetic testing for familial hypercholesterolemia. Iacocca, MA., Hegele, RA.[2018]

References

1. United States pubmed.ncbi.nlm.nih.gov

Clinical Genetic Testing for Familial Hypercholesterolemia: JACC Scientific Expert Panel. [2019]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Prevalence of genetically defined familial hypercholesterolemia and the impact on acute myocardial infarction in Taiwanese population: A hospital-based study. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Genotype-guided diagnosis in familial hypercholesterolemia: population burden and cascade screening. [2017]

4. England pubmed.ncbi.nlm.nih.gov

Genotype-guided diagnosis in familial hypercholesterolemia: clinical management and concerns. [2017]

5. Switzerland pubmed.ncbi.nlm.nih.gov

[A Family History of Hypercholesterolemia - the Role of Genetics]. [2023]

6. Ireland pubmed.ncbi.nlm.nih.gov

Mutational analysis and genotype-phenotype relation in familial hypercholesterolemia: The SAFEHEART registry. [2018]

7. United States pubmed.ncbi.nlm.nih.gov

Limited-Variant Screening vs Comprehensive Genetic Testing for Familial Hypercholesterolemia Diagnosis. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Integrating Patient-Reported Outcomes Into Clinical Genetic Testing for Familial Hypercholesterolemia. [2021]

9. Ireland pubmed.ncbi.nlm.nih.gov

Prevalence of familial hypercholesterolemia in patients with acute coronary syndrome in Japan: Results of the EXPLORE-J study. [2019]

10. Qatar pubmed.ncbi.nlm.nih.gov

Prevalence of cardiovascular events in genetically confirmed versus unconfirmed familial hypercholesterolaemia. [2021]

11. England pubmed.ncbi.nlm.nih.gov

Recent advances in genetic testing for familial hypercholesterolemia. [2018]