Advancing Cardiac Care Unit-based Rapid Assessment and Treatment of hypErcholesterolemia

Study Overview
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Brief Summary
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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.

Detailed Description
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Familial hypercholesterolemia (FH) is an inherited condition characterized by elevated low-density lipoprotein cholesterol (LDL-C) levels and premature atherosclerotic cardiovascular disease (ASCVD). Despite being the most common inherited cardiovascular disorder, it is still highly underdiagnosed and undertreated worldwide. The Advancing Cardiac Care Unit-based Rapid Assessment and Treatment of hypErcholesterolemia (ACCURATE) study was designed to test the hypothesis that opportunistic genetic testing for FH among patients hospitalized for acute coronary syndrome (ACS) will increase the diagnosis of FH and improve patient outcomes. 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 will consist of a control group of patients presenting with ACS who will be treated according to usual standard-of-care. The second cohort will consist of patients presenting with ACS in whom research-based genetic testing for FH will be performed during hospitalization and the results returned to the 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-C level achieved, and the proportion of patients reaching guideline recommended lipid targets in the 12 months after the index ACS. ACCURATE represents the first clinical trial of genetic testing for FH in the acute cardiac care setting and is expected to help identify optimal approaches to increase the diagnosis and treatment of FH.

Official Title
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The Advancing Cardiac Care Unit-based Rapid Assessment and Treatment of hypErcholesterolemia (ACCURATE) Study

Conditions
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Familial Hypercholesterolemia, Familial Hypercholesterolemia Due to Genetic Defect of Apolipoprotein B, Familial Hypercholesterolemia Due to Heterozygous LDL Receptor Mutation, Familial Hypercholesterolemia - Heterozygous, Acute Coronary Syndrome, NSTEMI - Non-ST Segment Elevation MI, STEMI, Familial Hypercholesterolemia With Hyperlipemia

Intervention / Treatment
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* Diagnostic Test: Research-based genetic test for Familial Hypercholesterolemia


Participation Criteria
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Eligibility Criteria
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Age <60 years AND Admitted to an acute cardiac unit with either: A ST elevation myocardial infarction (STEMI), or A non-ST elevation myocardial infarction (NSTEMI) AND Maximum lipid level at the time of admission or during the prior 1 year of LDL level ≥4 mmol/L (154 mg/dL) if not on a statin, or LDL-C level ≥2.5 mmol/L (96 mg/dL) if on a statin prior to presentation, or Non-HDL-C ≥4.6 mmol/L (177 mg/dL) if LDL-C not available

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Two sequential groups of patients will be recruited. The first cohort will consist of a control group of patients presenting with acute coronary syndrome who will be treated according to usual standard-of-care. The second cohort will consist of patients presenting with acute coronary syndrome in whom research-based genetic testing for FH will be performed during hospitalization and the results returned to the treating physicians.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Observation<br>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. | |
| Experimental: Active-testing<br>Those admitted between 6-18 months of the study meeting the inclusion criteria. Saliva samples will be collected for DNA testing. | Diagnostic Test: Research-based genetic test for Familial Hypercholesterolemia<br>* Next-generation targeted sequencing assay to identify DNA variants in genes known to cause Familial Hypercholesterolemia<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with a new diagnosis of FH |  | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients in whom lipid-lowering medication intensified, as defined by an increase the dose of statin, or the addition of a non-statin lipid-lowering medication, in the first year after ACS |  | 1 year | 
| Lowest LDL-cholesterol (LDL-C) level achieved in the first year after ACS |  | 1 year | 
| Proportion of patients who achieve guideline recommended lipid targets in the first year after ACS | Canadian Cardiovascular Society Guidelines: LDL-C <1.8 mmol/L European Society of Cardiology Guidelines: ≥50% LDL-C reduction from baseline and LDL-C <1.4 mmol/L | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Familial hypercholesterolemia, hyperlipoproteinemia Type II, hyperlipoproteinemia type 2, familial hypercholesterolaemia, myocardial infarction, acute coronary syndrome, ST-elevated myocardial infarction, STEMI, non-ST-elevation myocardial infarction, NSTEMI, heart attack, genetic investigation, genetic testing, proprotein convertase subtilisin kexin 9, PCSK9, low-density lipoprotein receptor, LDLR, apolipoprotein B, APOB, low-density lipoprotein cholesterol, LDL-C