Angina Pectoris, CAD, Cardiovascular Diseases, CHD, Chest Pain, Coronary Artery Disease, Coronary Heart Disease, CVD
Conditions
Keywords
Corus CAD, ASGES, Age/Sex/Gene Expression Score, Gene Expression, GES, CAD, CVD, CHD, Clinical Utility, Precision Medicine, Primary care, Coronary Artery Disease, Angina Pectoris, Chest Pain, Cardiovascular Disease, Coronary Heart Disease, IMPACT, IMPACT-PCP
Brief summary
This is a prospective, multi-center study examining the clinical impact of the Corus CAD (Age/Sex/Gene Expression score - ASGES) assay in approximately 250 evaluable subjects with no history of obstructive coronary artery disease who now present with chest pain or anginal-equivalent symptoms to a primary care physician (PCP) for evaluation.
Detailed description
In symptomatic patients with or without prior cardiac testing, the PCP will initially decide the subject's pretest probability for coronary artery disease (CAD) based on the subject's risk factors and quality of chest pain (typical or atypical), or anginal equivalent (e.g., jaw, arm pain, or unexplained shortness of breath) and consider the results of prior testing, if applicable. The initial questionnaire will capture the PCP's initial clinical impression and decision ('preliminary decision') on how to further evaluate and manage the patient. A Corus CAD (Age/Sex/Gene Expression score - ASGES) assay will be performed at the PCP's office. After the PCP has received the Corus CAD (ASGES) result (approximately 2-3 days later), the PCP will decide on the appropriate evaluation and management of the patient ('final decision') using the Corus CAD (ASGES) result in conjunction with his/her clinical impression and/or other clinical data available. The primary aim of this study is to evaluate whether the Corus CAD (ASGES) test results is associated with a change in the PCPs' diagnostic evaluation and management of patients as compared to their initial testing and treatment decisions. Since it takes approximately two days for the physician to receive the result of the Corus CAD (ASGES), symptomatic subjects with unstable angina, or suspicion for myocardial infarction will be excluded from the study. A follow-up phone call and a detailed questionnaire will be performed at 30 + 15 days, from the time of blood draw, to assess the triage decision, such as referral to any subspecialists (cardiologist, gastroenterologist, and pulmonologist), cardiac diagnostic tests performed, cardiac procedures performed, and results of these cardiac tests and procedures.
Interventions
DIAGNOSTIC_TESTCorus CAD
Age/Sex/Gene Expression Score (ASGES)
Sponsors
CardioDx
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Stable chest pain, typical or atypical angina or anginal equivalent 2. The patient has signed the appropriate Institutional Review Board approved Informed Consent Form.
Exclusion criteria
1. History of myocardial infarction 2. Current Myocardial infarction (MI) or acute coronary syndrome. 3. Current New York Heart Association (NYHA) class III or IV congestive heart failure symptoms. 4. Any previous coronary revascularization. 5. Any individuals with : * Diabetes * Suspected unstable angina * Systemic infections * Systemic inflammatory conditions 6. Any individuals currently taking: * Steroids * Immunosuppressive agents * Chemotherapeutic agents 7. Any Major Surgery within 2 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Clinicians' Treatment Decision After Age/Sex/Gene Expression Score | pre- and post- gene expression testing results (on average 2-3 days to receive ASGES) | The primary objective was to assess whether the Age/Sex/Gene Expression Score (ASGES) altered clinicians' evaluations, defined by a change in patient management from preliminary to final decision. The change was prospectively defined as a downgrade or upgrade in intensity of the diagnostic plan based on the following hierarchical categories:(1) no further cardiac testing or treatment, (2) lifestyle changes or medical therapy, (3) stress testing (with or without imaging) or computed tomography/coronary angiography, or (4) invasive coronary angiography. The ASGES algorithm comprises expression values for 23 genes from peripheral blood cells in 6 terms, patient age, and sex. The changes in gene expression are quantified using an algorithm that generates a ASGES ranging from 1 to 40. A score \<=15 indicates a low risk of underlying obstructive coronary disease. The ASGES has a negative predictive value of 96% for ASGES \<=15 in a population referred to myocardial perfusion imaging. |
Countries
United States
Participant flow
Recruitment details
Subjects are enrolled at multiple participating primary care practices from site initiation (Apr-Jun 2012) thru January 2013.
Pre-assignment details
327 screened, 275 met inclusion/exclusion. Subjects were excluded from the analysis set if no Corus CAD test could be resulted (7) or if additional information was available and used in making post treatment decisions (3) or did not inclusion/exclusion (discovered after research blood sample draw). Analysis set was 251.
Participants by arm
| Arm | Count |
|---|---|
| All Subjects Subjects are enrolled at multiple participating primary care practices. The main inclusion criterion for enrollment is the occurrence of chest pain (or anginal equivalent) in a patient without known significant CAD or a history of prior myocardial infarction. | 251 |
| Total | 251 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 2 |
Baseline characteristics
| Characteristic | All Subjects |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 69 Participants |
| Age, Categorical Between 18 and 65 years | 182 Participants |
| Age, Continuous | 56.2 years STANDARD_DEVIATION 13 |
| Age/Sex/Gene Expression Score | 16 unitless STANDARD_DEVIATION 10 |
| Body Mass Index (BMI) | 29.7 kg/m^2 STANDARD_DEVIATION 6.7 |
| Region of Enrollment United States | 251 participants |
| Sex: Female, Male Female | 140 Participants |
| Sex: Female, Male Male | 111 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 251 |
| serious Total, serious adverse events | 0 / 251 |
Outcome results
Primary
Change in Clinicians' Treatment Decision After Age/Sex/Gene Expression Score
The primary objective was to assess whether the Age/Sex/Gene Expression Score (ASGES) altered clinicians' evaluations, defined by a change in patient management from preliminary to final decision. The change was prospectively defined as a downgrade or upgrade in intensity of the diagnostic plan based on the following hierarchical categories:(1) no further cardiac testing or treatment, (2) lifestyle changes or medical therapy, (3) stress testing (with or without imaging) or computed tomography/coronary angiography, or (4) invasive coronary angiography. The ASGES algorithm comprises expression values for 23 genes from peripheral blood cells in 6 terms, patient age, and sex. The changes in gene expression are quantified using an algorithm that generates a ASGES ranging from 1 to 40. A score \<=15 indicates a low risk of underlying obstructive coronary disease. The ASGES has a negative predictive value of 96% for ASGES \<=15 in a population referred to myocardial perfusion imaging.
Time frame: pre- and post- gene expression testing results (on average 2-3 days to receive ASGES)
Population: The study sites included 9 clinicians at 4 community-based primary care practices who assessed all participants with a valid ASGES.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| No Tests/Treatment | Change in Clinicians' Treatment Decision After Age/Sex/Gene Expression Score | Medical Therapy pre-ASGES, ASGES ,=15 (n=33) | 25 number of subjects |
| No Tests/Treatment | Change in Clinicians' Treatment Decision After Age/Sex/Gene Expression Score | Stress test pre-ASGES, ASGES >15 (n=65) | 5 number of subjects |
| No Tests/Treatment | Change in Clinicians' Treatment Decision After Age/Sex/Gene Expression Score | Stress Tes pre-ASGES, ASGES <=15 (N=53) | 45 number of subjects |
| No Tests/Treatment | Change in Clinicians' Treatment Decision After Age/Sex/Gene Expression Score | Medical Therapy pre-ASGES, ASGES >15 (n=15) | 5 number of subjects |
| No Tests/Treatment | Change in Clinicians' Treatment Decision After Age/Sex/Gene Expression Score | NoTests/Treatment pre-ASGES, ASGES >15 (n=43) | 3 number of subjects |
| No Tests/Treatment | Change in Clinicians' Treatment Decision After Age/Sex/Gene Expression Score | No Tests/Treatment pre-ASGES, ASGES <=15 (n=40) | 38 number of subjects |
| No Tests/Treatment | Change in Clinicians' Treatment Decision After Age/Sex/Gene Expression Score | Invasive Coronary Angio pre-ASGES, ASGES >15 (n=1) | 1 number of subjects |
| No Tests/Treatment | Change in Clinicians' Treatment Decision After Age/Sex/Gene Expression Score | Invasive Coronary Angio pre-ASGES, AGES >=15 (n=1) | 1 number of subjects |
| Medical Therapy | Change in Clinicians' Treatment Decision After Age/Sex/Gene Expression Score | Medical Therapy pre-ASGES, ASGES >15 (n=15) | 2 number of subjects |
| Medical Therapy | Change in Clinicians' Treatment Decision After Age/Sex/Gene Expression Score | No Tests/Treatment pre-ASGES, ASGES <=15 (n=40) | 1 number of subjects |
| Medical Therapy | Change in Clinicians' Treatment Decision After Age/Sex/Gene Expression Score | NoTests/Treatment pre-ASGES, ASGES >15 (n=43) | 1 number of subjects |
| Medical Therapy | Change in Clinicians' Treatment Decision After Age/Sex/Gene Expression Score | Stress Tes pre-ASGES, ASGES <=15 (N=53) | 5 number of subjects |
| Medical Therapy | Change in Clinicians' Treatment Decision After Age/Sex/Gene Expression Score | Stress test pre-ASGES, ASGES >15 (n=65) | 6 number of subjects |
| Medical Therapy | Change in Clinicians' Treatment Decision After Age/Sex/Gene Expression Score | Invasive Coronary Angio pre-ASGES, AGES >=15 (n=1) | 0 number of subjects |
| Medical Therapy | Change in Clinicians' Treatment Decision After Age/Sex/Gene Expression Score | Invasive Coronary Angio pre-ASGES, ASGES >15 (n=1) | 0 number of subjects |
| Medical Therapy | Change in Clinicians' Treatment Decision After Age/Sex/Gene Expression Score | Medical Therapy pre-ASGES, ASGES ,=15 (n=33) | 7 number of subjects |
| Stress Test | Change in Clinicians' Treatment Decision After Age/Sex/Gene Expression Score | Medical Therapy pre-ASGES, ASGES ,=15 (n=33) | 1 number of subjects |
| Stress Test | Change in Clinicians' Treatment Decision After Age/Sex/Gene Expression Score | Stress test pre-ASGES, ASGES >15 (n=65) | 53 number of subjects |
| Stress Test | Change in Clinicians' Treatment Decision After Age/Sex/Gene Expression Score | Invasive Coronary Angio pre-ASGES, AGES >=15 (n=1) | 0 number of subjects |
| Stress Test | Change in Clinicians' Treatment Decision After Age/Sex/Gene Expression Score | NoTests/Treatment pre-ASGES, ASGES >15 (n=43) | 39 number of subjects |
| Stress Test | Change in Clinicians' Treatment Decision After Age/Sex/Gene Expression Score | Invasive Coronary Angio pre-ASGES, ASGES >15 (n=1) | 0 number of subjects |
| Stress Test | Change in Clinicians' Treatment Decision After Age/Sex/Gene Expression Score | No Tests/Treatment pre-ASGES, ASGES <=15 (n=40) | 1 number of subjects |
| Stress Test | Change in Clinicians' Treatment Decision After Age/Sex/Gene Expression Score | Stress Tes pre-ASGES, ASGES <=15 (N=53) | 3 number of subjects |
| Stress Test | Change in Clinicians' Treatment Decision After Age/Sex/Gene Expression Score | Medical Therapy pre-ASGES, ASGES >15 (n=15) | 7 number of subjects |
| Invasive Angiography | Change in Clinicians' Treatment Decision After Age/Sex/Gene Expression Score | No Tests/Treatment pre-ASGES, ASGES <=15 (n=40) | 0 number of subjects |
| Invasive Angiography | Change in Clinicians' Treatment Decision After Age/Sex/Gene Expression Score | Stress Tes pre-ASGES, ASGES <=15 (N=53) | 0 number of subjects |
| Invasive Angiography | Change in Clinicians' Treatment Decision After Age/Sex/Gene Expression Score | Stress test pre-ASGES, ASGES >15 (n=65) | 1 number of subjects |
| Invasive Angiography | Change in Clinicians' Treatment Decision After Age/Sex/Gene Expression Score | NoTests/Treatment pre-ASGES, ASGES >15 (n=43) | 0 number of subjects |
| Invasive Angiography | Change in Clinicians' Treatment Decision After Age/Sex/Gene Expression Score | Medical Therapy pre-ASGES, ASGES ,=15 (n=33) | 0 number of subjects |
| Invasive Angiography | Change in Clinicians' Treatment Decision After Age/Sex/Gene Expression Score | Invasive Coronary Angio pre-ASGES, ASGES >15 (n=1) | 0 number of subjects |
| Invasive Angiography | Change in Clinicians' Treatment Decision After Age/Sex/Gene Expression Score | Invasive Coronary Angio pre-ASGES, AGES >=15 (n=1) | 0 number of subjects |
| Invasive Angiography | Change in Clinicians' Treatment Decision After Age/Sex/Gene Expression Score | Medical Therapy pre-ASGES, ASGES >15 (n=15) | 1 number of subjects |
Comparison: The proportion of patients whose final treatment plan changes from the preliminary will be estimated, and a one-sided binomial test with alpha level of .05 will be used to test whether it is greater than 10%.~This is the level at which it is assumed that patient management has been modified by a practically important amount.p-value: <0.001one-sided binomial with alpha level of 0