Genetic Testing for Acute Coronary Syndrome

(ACCURATE Trial)

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether genetic testing for Familial Hypercholesterolemia (FH) can enhance the diagnosis and treatment of patients who have experienced a heart attack. The study examines the number of new FH cases identified and how this impacts patient care, such as changes in medications to lower cholesterol levels. The trial includes two groups: one receives the genetic test, while the other follows the standard care for heart attack patients. Individuals who have had a heart attack and have high cholesterol, particularly those under 60, may be suitable candidates. As an unphased study, this trial provides a unique opportunity to contribute to understanding how genetic testing can improve heart attack care.

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 prior data suggests that this genetic testing is safe?

Research has shown that genetic testing for Familial Hypercholesterolemia (FH) is safe and can improve health outcomes. Studies have found that diagnosing FH through genetic tests allows for more effective management than regular medical check-ups alone. Knowing if someone has FH through genetic testing can lead to improved treatment plans.

No specific reports indicate negative effects from the genetic testing itself. The process typically involves taking a saliva sample, which is easy and generally well-tolerated. Overall, evidence suggests that this genetic testing is safe for patients. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the genetic testing for Familial Hypercholesterolemia in patients with Acute Coronary Syndrome because it offers a unique approach to identifying genetic risk factors. Unlike standard treatments that focus on managing symptoms with medications like statins, this genetic test aims to pinpoint individuals who may have a hereditary predisposition to high cholesterol. By collecting DNA from saliva samples, this method could provide a more personalized treatment plan, potentially leading to more effective prevention strategies for future cardiac events. This innovative approach could revolutionize how we understand and treat heart conditions by targeting the root cause rather than just addressing the symptoms.

What evidence suggests that genetic testing for Familial Hypercholesterolemia is effective for diagnosing FH in patients with acute coronary syndrome?

Research has shown that genetic testing can identify Familial Hypercholesterolemia (FH) in individuals who might otherwise be overlooked. In this trial, participants in the active-testing arm will undergo genetic testing for FH. One study found that about 9% of patients with acute coronary syndrome and high LDL cholesterol also had FH. Genetic tests can detect FH mutations that regular methods might miss, aiding doctors in creating more effective treatment plans, such as prescribing stronger cholesterol-lowering medications. Thus, genetic testing could improve heart health for those with FH. ^{3 4 6 7 8}

Who Is on the Research Team?

Liam Brunham, MD PhD

Principal Investigator

University of British Columbia

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S073510971739246X

Genetically Confirmed Familial Hypercholesterolemia in ... The prevalence of genetically confirmed FH in patients with ACS age ≤65 years and with LDL-C levels ≥160 mg/dl is high (approximately 9%).

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10932851/

Genetic testing for familial hypercholesterolemia - PMC Genetic testing can facilitate the identification of FH cases who may be missed by clinical diagnostic criteria, improve risk stratification beyond LDL-C and ...

3. jacc.org jacc.org/doi/10.1016/j.jacc.2018.05.044

Clinical Genetic Testing for Familial Hypercholesterolemia Genetic testing facilitates family-based cascade testing for FH. Because FH is an autosomal dominant disorder, screening the at-risk relatives of a patient ...

4. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1111/joim.12812

Genetic testing for familial hypercholesterolemia among ... Five patients were detected on the panel, and further testing of the remaining 111 patients detected an additional 3 FH-causative mutations.

5. centerwatch.com centerwatch.com/clinical-trials/listings/condition/25012/hypercholesterolemia

Hypercholesterolemia Clinical Research Trials ACCURATE is a non-randomized, controlled trial of patients <60 years old admitted to an acute cardiac unit with ACS and elevated LDL-C levels. The first cohort ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9470216/

Genetic Testing for Familial Hypercholesterolemia: Health ... Our review found that genetic testing to diagnose FH improves several health outcomes (GRADE: Moderate) compared with clinical evaluation without a genetic ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT02870660

Familial Hypercholesterolemia Amongst Patients With ... Studies demonstrated direct connection between familial hypercholesterolemia and occurrence of premature ACS. Investigators intent to detection of FH amongst ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9363594/

Prevalence and prognosis of molecularly defined familial ... The prevalence of molecularly defined FH in enrolled patients was 26.9%, and coronary artery lesions were more severe in patients with FH than in those without.