- Coronary artery disease is the most common form of cardiovascular disease in Canada.
- A new blood test, Corus CAD, combines age, sex, and gene expression in an algorithm to determine the likelihood a person has obstructive coronary artery disease.
- Corus CAD is intended for use in patients with suspected undiagnosed obstructive coronary artery disease.
- There is interest in assessing Corus CAD in patient groups such as women with obstructive coronary artery disease who often have atypical symptoms and may not always be appropriately referred for follow-up testing.
- Studies have evaluated whether Corus CAD may help clinicians rule out coronary artery disease in some patients when used as a complement to patient history, risk factors, symptoms, physical examination, and other diagnostic tests.
Coronary Artery Disease
Coronary artery disease (also called ischemic heart disease) is the most common type of cardiovascular disease in Canada.1,2 It occurs when a build-up of plaque (atherosclerosis) narrows the arteries that bring blood to the heart, limiting the amount of oxygen the heart receives (ischemia).1-3 Untreated coronary artery disease can lead to heart attack, stroke, or death.2
People with coronary artery disease often experience chest pain (angina) or shortness of breath.1,2 Other symptoms of coronary artery disease include fatigue, pain, dizziness, and sensations of suffocating or burning starting from the centre of the chest and sometimes moving to other parts of the upper body, such as the arm, neck, or back.2 Women with coronary artery disease often experience more subtle symptoms, such as vague chest discomfort.2,3
People presenting with stable symptoms of coronary artery disease are diagnosed using a combination of methods, including history, physical examination, symptom characteristics, risk factors (such as age, sex, excess body weight, and smoking), and diagnostic tests (such as non-invasive stress testing and invasive angiography). (see Box 1).2-5
A person’s DNA contains all the genetic information needed to build an estimated 20,000 different proteins.12 Gene expression is the process by which genetic information encoded in DNA is used to generate gene products (e.g., proteins). The quantity and timing at which gene products are generated depends on many factors, including the type of cell (for example, heart or lung) and the presence of disease.12
Advances in science have allowed for the discovery and study of many biological markers (biomarkers) of gene expression.12 When used alone or, more commonly, in combination with known risk factors, biomarkers can help predict the possibility of developing a disease, help diagnose the presence of disease, or determine how a disease will progress in an individual patient.12
A new test that measures the level of expression of genes associated with coronary artery disease, and incorporates age and sex, is intended to help clinicians assess the likelihood of obstructive coronary artery disease in patients presenting with stable symptoms.
Corus CAD13 (CardioDx, Redwood City, CA), is a blood test intended for use in people with symptoms suggestive of stable coronary artery disease to help clinicians rule out the possibility of obstructive coronary artery disease or help them plan for further testing and management.14
A Corus CAD sample kit contains all the materials necessary for the physician to take a patient’s blood sample and send it to CardioDx for processing and analysis.14,15 Testing involves the following steps:14-17
- Taking a standard venous blood draw from the patient during a clinician office visit
- Completing a patient profile and sending the sample to CardioDx in a temperature controlled package
- Processing the sample at CardioDx’s laboratory
- Reviewing test results, presented as an Age/Sex/Gene Expression Score (ASGES), through CardioDx’s online portal or by fax.
Once the blood sample is received by CardioDx, RNA is purified from the sample, complementary DNA is synthesized, and quantitative real-time polymerase chain reaction (qRT-PCR) is used.16 Test results are calculated using the age, sex, and six gene expression terms, composed of 23 genes associated with coronary artery disease.16,18 Some of the gene expression terms are unique to men, some are unique to women, and others occur in both sexes.18 Following analysis, an ASGES is reported on a 40-point scale with a score of 1 representing a low likelihood of disease and 40 representing a high likelihood of disease.16 The calculations used to determine the ASGES differ between men and women based on age, specific genes, and weighting of genes included in the test.16 Test results are typically available to clinicians in a few days.14
Corus CAD is not intended for use in people who have previously had a heart attack or undergone cardiac revascularization procedures, who have a history of obstructive coronary artery disease, high-risk unstable angina, systemic infectious or inflammatory conditions, or diabetes, who are taking steroids or drugs that suppress the immune system, or who are receiving chemotherapy.19
Common Tests for Coronary Artery Disease
Clinical Prediction Rules
- Diamond-Forrester score — A model for assessing patients with symptoms of coronary artery disease that incorporates age, sex, and type of chest pain to determine their likelihood of having coronary artery disease before testing.6
- Exercise Stress Testing — Monitoring the electrical activity in the heart, while patients walk on a treadmill as the speed and incline gradually increase.7
- Stress Echocardiography — Using ultrasound to create images of the heart, before and after walking on a treadmill, to evaluate the presence of heart-wall motion abnormalities that indicate inadequate coronary blood flow.8
- Myocardial perfusion imaging — Using a combination of exercise stress testing and imaging to see the blood supply to the heart. Patients are injected with radioactive tracers that circulate through the blood. A gamma camera takes pictures of the heart while exercising and at rest. This technique can be performed using single photon emission computed tomography or positron emission tomography.9
- Coronary computed tomography (CT) angiography — Creating a cross-sectional or 3-D picture of the heart using X-ray images to determine if there are plaque or calcium deposits inside the arteries. CT angiography requires use of a contrast agent to show the blood vessels.10
- Coronary angiography — Inserting a catheter (a long flexible tube) into an artery in the wrist or groin and moving it to the heart, where a contrast agent is released and X-ray images are taken to detect blockages in the coronary arteries.11
The Corus CAD test is not currently available in Canada. The manufacturer intends to explore marketing the test in Canada in the future (David Levison, Chief Strategy Officer, CardioDx, Inc., Redwood City, CA: personal communication, 2017 Nov 6).
In the US, the test is available as a laboratory-developed test certified under the Clinical Laboratory Improvement Amendments.20
Canadian pricing for the Corus CAD test is not available. According to the manufacturer’s documentation, the US cost of the test for uninsured patients is US$1,245.21
Who Might Benefit?
An estimated 2.4 million Canadians live with coronary artery disease.22 In 2005-2006, 6.5% of all hospitalizations (excluding those for pregnancy) in Canada were related to coronary artery disease.23 In 2004, 17.3% of all deaths were attributed to coronary artery disease.23 Thousands of Canadians are hospitalized or die because of a heart attack each year.23 A 2016 report from the Chief Public Health Officer found that Canadians with lower household income, men, people over the age of 50, and Indigenous people were more likely to have cardiovascular disease.24
It is more difficult to diagnose coronary artery disease in women because of differences in presentation of symptoms and differences in the biology of the heart. Women are more likely to be incorrectly diagnosed with coronary artery disease using non-invasive methods, leading to increased use of more invasive diagnostic procedures.2,25
The Corus CAD test is only intended for use in a specific population of patients presenting with symptoms suggestive of coronary artery disease (see the Technology section). Many Canadians, such as people with diabetes, of whom 2% to 19% develop coronary artery disease,26 would not benefit from receiving this test.
These bulletins are not systematic reviews and do not involve a detailed critical appraisal or a detailed summary of study findings. Rather they present an overview of the technology and available evidence. They are not intended to provide recommendations for or against a particular technology.
Literature Search Strategy
A peer-reviewed literature search was conducted using the following bibliographic databases: MEDLINE, PubMed, Embase, and the Cochrane Library (2017, Issue 05). Grey literature was identified by searching relevant sections of the Grey Matters checklist (https://www.cadth.ca/grey-matters). No methodological filters were applied. The search was limited to English-language documents published between January 1, 2012, and May 8, 2017. Regular alerts updated the search until project completion; only citations retrieved before February 8, 2018, were incorporated into the analysis. Conference abstracts were excluded from the search results.
One author screened the literature search results and reviewed the full text of all potentially relevant studies. Studies were considered for inclusion if the intervention used included gene expression testing for obstructive coronary artery disease. Conference abstracts and grey literature were included when they provided additional information to that available in the published studies.
A draft bulletin was reviewed by two clinical experts and the manufacturer.
In Canada, obstructive coronary artery disease is commonly defined as greater than 50% stenosis in the left main coronary artery or greater than 70% stenosis in an epicardial artery (on the outer surface of the heart).27,28
The 2014 Canadian Cardiovascular Society Guidelines for the Management of Stable Ischemic Heart Disease outline the current evidence-based approach for diagnosing coronary artery disease in Canada.4 Diagnosing coronary artery disease is complex and may involve both invasive and non-invasive testing (see Box 1), depending on a patient’s history, physical examination, and initial test results.4 All patients with suspected coronary artery disease should undergo a thorough history and physical examination to evaluate symptoms and risk factors for coronary artery disease (such as age, sex, history of smoking, and physical inactivity).4 The results of this initial examination will inform a pretest probability (how likely it is a patient has coronary artery disease before diagnostic testing) that can be used to determine a testing plan.4
Depending on the patient and the pretest probability of coronary artery disease, the guidelines recommend clinicians refer patients for non-invasive or invasive testing.4 The guidelines note that selecting the appropriate non-invasive test for a patient is complicated by the fact that no single test can provide all the information a clinician may need to make a diagnosis.4
In addition to the common tests listed in Box 1, if available, more specialized testing methods, such as positron emission tomography, CT perfusion scanning, or MRI, can also be considered to complement, or serve as an alternative to, other tests.4 Clinicians are encouraged to consider minimizing patient exposure to radiation associated with some types of testing.4
We identified 19 studies of the Corus CAD test.18,29-46 All but one of the studies43 were funded or co-authored by the manufacturer, or by authors who have received funding from CardioDx.
Six studies form the central body of evidence of the validity and clinical utility of the test:
- PREDICT — Personalized Risk Evaluation and Diagnosis in the Coronary Tree29
- COMPASS — Coronary Obstruction Detection by Molecular Personalized Gene Expression30
- IMPACT-CARD — Investigation of a Molecular Personalized Coronary Gene Expression Test on Cardiology Practice Pattern31
- IMPACT-PCP — Primary Care Providers Use of a Gene Expression Test in Coronary Artery Disease32
- REGISTRY I — Investigation of a Novel Gene Expression Test for the Diagnosis of Obstructive CAD on Physician’s Practice Pattern33
- PRESET registry — A Registry to Evaluate Patterns of Care Associated with the use of Corus CAD in Real World Clinical Settings.34
Of the remaining 13 studies:
- Seven were secondary analyses18,35-40
- Three were smaller studies of clinical utility that may be of interest to readers41-43
- Three examined the costs of using the test.44-46
Information about the six central studies and secondary analyses is presented by outcome in Table 1. Additional information on the validity and clinical utility of the test that may be of interest to readers is highlighted later in this section. Studies of other uses of the Corus CAD test or ASGES are presented in the Concurrent Developments section.
The six central studies of the Corus CAD test29-34 generally included patients with no history of diabetes who presented with typical or atypical symptoms suggestive of coronary artery disease. Obstructive coronary artery disease was defined as one or more lesions (plaque) causing at least 50% loss in the diameter (stenosis) of a major artery. Although the studies all use the Corus CAD test, the outcome measured is ASGES; that is, the score produced by CardioDx after samples are received.
The studies used a threshold of 15 (14.75 in PREDICT29) out of 40 when interpreting the Corus CAD test results. A score of 15 or lower is considered low (at low risk of currently having obstructive coronary artery disease) and a score greater than 15 is considered elevated (at higher risk of currently having obstructive coronary artery disease). Corus CAD was also analyzed as a continuous variable (score 1-40) in the PREDICT and COMPASS studies.29,30 These studies investigated test performance and change in clinician practice.
The clinical performance of the Corus CAD test was validated in two key studies (PREDICT and COMPASS: Table 1), both conducted at multiple sites across the US.29,30 Researchers also conducted secondary analyses of the PREDICT study to explore the performance of the test in women18,36 and reported on major adverse cardiovascular events (MACE) and coronary procedures after ASGES testing.18,35,36
Four central studies (IMPACT-CARD, IMPACT-PCP, REGISTRY I, and PRESET registry; Table 1) investigated the impact that using the Corus CAD test in clinical practice may have on patient management in the US.31,33,34,47 Two smaller studies, reported as conference abstracts, also examined similar outcomes.42,43 Two US cost studies also evaluated the impact of Corus CAD use on the number of patients referred for coronary angiography and other diagnostic tests.44,45
The impact of Corus CAD on the care of women was studied in a secondary analysis of data from the IMPACT-PCP and REGISTRY I studies,38 in two secondary analyses of data from the PRESET registry (reported as conference abstracts),39,40 and one additional study (reported as a conference abstract).41 In addition, a secondary analysis of the PRESET registry evaluated the impact of Corus CAD on care in patients over the age of 65.37
None of the studies reported whether changes in clinician behaviour resulted in changes in direct health-related outcomes in patients.
Nine of the clinical utility studies also included secondary outcomes of MACE and coronary procedures.31-34,37-41
The costs of using the Corus CAD test in US health care settings were modelled in one budget impact analysis45 and one cost-utility analysis,44 both published in 2014. Costs considered in both studies included those for different tests and procedures and those for subsequent treatments.44,45 One study also considered the costs of lost patient time and heart attacks,44 while the other study also considered the costs of office visits.45 An economic analysis of the IMPACT-CARD study was also reported as a conference abstract.46
Table 1: Summary of Clinical and Cost Evidence
|Study Name, Author, Publication Year, Location||Patient Characteristics; Sample Size (Incl. in Analysis)||Study Design||Intervention||Comparator or Reference Standard||Outcomes||Key Findings|
|PREDICT, Rosenberg et al., 2010, US29||Pts referred for diagnostic CA angiography with a history of chest pain or atypical symptoms suggestive of CAD disease, or a high-risk of CAD; n = 1,569 (649 in validation arm)
Prevalence of obstructive CAD = 37%
||" … the sensitivity was 85% with a specificity of 43%, corresponding to [NPV and PPV] of 83% and 46% respectively.”
“The primary end point AUC was 0.70 …” (p. 6)29
|Secondary analysis using data from 1,160 pts (492 women and 668 men)18
Prevalence of obstructive CAD in women = 22%
|Secondary analysis of 1,160 pts (850)35||
“There were 17 [pts] with MACE, of which 15 occurred more than 30 days after index angiogram;
|Secondary analysis of 1,328 pts (1,266)36d||
“A total of 330 [pts] (26%) had procedures or MACE within 30 days and 21 (2.4%) had
|IMPACT-CARD, McPherson et al., 2013, US31||
Pts with symptoms suggestive of CAD who did not have
||Pt care plan with ASGES||Pt care plan without ASGES||
|IMPACT-PCP, Herman et al, 2013, US32||Pts without diabetes presenting to their primary care cliniciani with suspected CAD; n = 261 patients (251)||
||Pt care plan with ASGES||Pt care plan without ASGES||
|REGISTRY I, Ladapo et al., 2015, US33||
Primary care pts who have received the Corus CAD test; n = 342
|Ladapo et al., 2015, US38||320 women enrolled in the IMPACT-PCP47 and REGISTRY I33 studies||
|PRESET registry, Ladapo et al., 2017, US34||
Primary care pts who have received the Corus CAD test; n = 934 (566)
|Secondary analysis of 176 pts over the age of 65.37||
|Secondary analysis of 369 women39d||
|Secondary analysis of 288 women40d||
ASGES = Age/Sex/Gene Expression Score; AUC = area under the curve; CA = coronary angiography; CAD = coronary artery disease; COMPASS = Coronary Obstruction Detection by Molecular Personalized Gene Expression; CT = computed tomography; D-F = Diamond and Forrester Chest Pain Prediction Rule; IMPACT-CARD = Investigation of a Molecular Personalized Coronary Gene Expression Test on Cardiology Practice Pattern; IMPACT-PCP = Primary Care Providers Use of a Gene Expression Test in Coronary Artery Disease; MACE = major adverse cardiac event; MI = myocardial infarction; MPI = myocardial perfusion imaging; NA = not applicable; NPV = negative predictive value; OR = odds ratio; PPV = positive predictive value; PREDICT = Personalized Risk Evaluation and Diagnosis in the Coronary Tree; PRESET registry = A Registry to Evaluate Patterns of Care Associated with the use of Corus CAD in Real World Clinical Settings; pt = patient; REGISTRY I = Investigation of a Novel Gene Expression Test for the Diagnosis of Obstructive CAD on Physician’s Practice Pattern; ROC = receiver operating characteristic; TIA = transient ischemic attack.
a Using ASGES cut off of 14.75.
b Calculated for a continuous ASGES (0-40), D-F, and MPI.
c Procedures and events occurring within 30 days of reference coronary angiography were considered baseline events.
d Only abstract format available.
e Using ASGES cut off of 15.
f Calculated for a continuous ASGES (0-40) and MPI.
g Upgrade in patient management = non-invasive cardiac testing (stress testing with or without imaging or CT angiography) or invasive coronary angiography; downgrade in patient management = medical therapy or no further testing.
h Includes historical controls
I Including doctors, nurse practitioners, and physician assistants.
j Upgrade in patient management = non-invasive cardiac testing (stress testing with or without imaging, CT angiography or coronary angiography) or invasive coronary angiography; downgrade in patient management = no additional testing or treatment, lifestyle changes, or medical therapy.
Other uses for ASGES results are being explored, as are other applications and uses of the Corus CAD test.
Detection of Atherosclerosis and Stenosis
A study of a subset of 610 patients from the PREDICT and COMPASS studies sought to determine whether ASGES was associated with plaque burden and luminal stenosis.48
Researchers have also investigated whether ASGES is associated with plaque volume and plaque type as measured by intravascular ultrasound (the use of soundwaves to see the inside of blood vessels) in a subset of 18 patients without diabetes from the ATLANTA study (originally designed to compare the measurement of plaque characteristics using CT angiography and intravascular ultrasound).49
Change in ASGES Over Time
Using data from the COMPASS studies, researchers have assessed the stability of ASGES after one year in patients who did not have a cardiac event or procedure since the completion of the COMPASS study.50
Effect of Exercise on ASGES
To understand if the Corus CAD test can be used after exercise, researchers evaluated the effect of exercise stress on ASGES in a pilot study of 20 patients (10 women and 10 men), who underwent exercise stress testing.51 The trial was funded by the manufacturer.51
Prediction of Future Cardiovascular Events
One study evaluated the correlation between Corus CAD scores and future cardiovascular events. A total of 1,116 patients from the PREDICT trial were followed for one year after angiography to monitor rates of major adverse cardiac events and cardiac interventions.35 A conference abstract also reported on this outcome.36
A subgroup analysis of 2,370 patients in the Prospective Multicenter Imaging Study for Evaluation of Chest Pain (PROMISE study) without diabetes who received a Corus CAD test evaluated whether patients with an elevated ASGES were at greater risk of death, heart attack, hospitalization for unstable angina, or revascularization, than were patients with a low ASGES.52
The relationship of ASGES to obstructive coronary artery disease in people with rheumatoid arthritis has also been studied.53
Other Gene Expression Testing Applications
A recent statement from the American Heart Association describes several other advances in gene expression testing and the impact they may have on our understanding and diagnosis of cardiovascular disease.12 Although there are many applications under investigation, Corus CAD is one of the few tests currently commercially available.
Both the IMPACT-PCP and REGISTRY I studies reported training times of five hours to implement the test in primary care practices in the US.32,33 The main purpose of training is to educate clinicians and other clinic personnel about the appropriate patient population for the test and how to interpret test results.
Validity in Different Ethnic Groups
A limitation of both the PREDICT and COMPASS studies is that they included primarily white patients.29,30
To evaluate performance in other ethnic and racial groups, researchers have reanalyzed data from the PREDICT study.50 Further research may help improve the understanding of the performance of Corus CAD in different ethnic groups.
Exposure to Radiation and Contrast Agents
Three reports of using Corus CAD in clinical practice mention that test results finding a low ASGES could affect exposure to, and adverse events associated with, radiation and contrast agents used in non-invasive and invasive tests for coronary artery disease by reducing or eliminating the need for additional tests.31,32,34 However, none of the studies evaluated these outcomes.
Several reports have noted the potential of ASGES to affect the number of patients referred for additional testing who actually have coronary artery disease.29-32,44,45 None of the studies evaluated this outcome.
The Corus CAD test has been studied in and is intended for use in a specific population of patients with suspected obstructive coronary artery disease. Studies of gene expression tests in small, carefully selected groups may not be generalizable to real-world clinical practice.54
No studies were identified that compare gene expression tests to more advanced methods of diagnostic testing for coronary artery disease. Studies are also needed to understand if changes in patient management result in better patient health outcomes through reducing unnecessary testing and associated adverse events.20,38,54
- Six types of cardiovascular disease [Internet]. Ottawa: Public Health Agency of Canada; 2017. [cited 2017 Sep 27]. Available from: https://www.canada. ca/en/public-health/services/chronic-diseases/cardiovascular-disease/six- types-cardiovascular-disease.html
- Coronary artery disease [Internet]. Ottawa: Heart & Stroke; 2017. [cited 2017 Sep 27]. Available from: https://www.heartandstroke.ca/heart/conditions/coronary-artery-disease
- Coronary artery disease (Atherosclerosis) [Internet]. Ottawa: University of Ottawa Heart Institute; 2009. [cited 2017 Oct 10]. Available from: https://www.ottawaheart.ca/heart-condition/coronary-artery-disease-atherosclerosis
- Mancini GB, Gosselin G, Chow B, Kostuk W, Stone J, Yvorchuk KJ, et al. Canadian Cardiovascular Society guidelines for the diagnosis and management of stable ischemic heart disease. Can J Cardiol [Internet]. 2014 Aug [cited 2017 Sep 27];30(8):837-49. Available from: http://www.onlinecjc.ca/article/S0828-282X(14)00356-0/pdf
- How is coronary heart disease diagnosed? [Internet]. Bethesda (MD): Department of Health and Human Services, National Institutes of Health; 2016 Jun 22. [cited 2017 Nov 23]. Available from: https://www.nhlbi.nih.gov/health/health-topics/topics/cad/diagnosis
- Diamond GA, Forrester JS. Analysis of probability as an aid in the clinical diagnosis of coronary-artery disease. N Engl J Med. 1979 Jun 14;300(24):1350-8.
- Treadmill exercise stress test [Internet]. Ottawa: University of Ottawa Heart Institute; 2017. [cited 2017 Oct 20]. Available from: https://www.ottawaheart.ca/test-procedure/treadmill-exercise-stress-test
- Echocardiogram [Internet]. Ottawa: University of Ottawa Heart Institute; 2017. [cited 2017 Oct 19]. Available from: https://www.ottawaheart.ca/test-procedure/echocardiogram
- Myocardial perfusion imaging (MPI) test [Internet]. Dallas (TX): American Heart Association; 2016 Sep 19. [cited 2017 Oct 19]. Available from: http://www.heart.org/HEARTORG/Conditions/HeartAttack/DiagnosingaHeartAttack/Myocardial-Perfusion-Imaging-MPI-Test_UCM_446352_Article.jsp#.WejBBmfbJeV
- Cardiac computed tomography (CT) scan [Internet]. Ottawa: University of Ottawa Heart Institute; 2017. [cited 2017 Oct 19]. Available from: https://www.ottawaheart.ca/test-procedure/cardiac-computed-tomography-ct-scan
- Angiogram (cardiac catheterization) [Internet]. Ottawa: University of Ottawa Heart Institute; 2017. [cited 2017 Oct 19]. Available from: https://www.ottawaheart.ca/test-procedure/angiogram-cardiac-catheterization
- Musunuru K, Ingelsson E, Fornage M, Liu P, Murphy AM, Newby LK, et al. The Expressed Genome in Cardiovascular Diseases and Stroke: Refinement, Diagnosis, and Prediction: A Scientific Statement From the American Heart Association. Circ Cardiovasc Genet [Internet]. 2017 Aug [cited 2017 Sep 27];10(4). Available from: http://circgenetics.ahajournals.org/content/10/4/e000037.long
- [Internet]. Redwood City (CA): CardioDx, Inc. CardioDx; 2017 [cited 2017 Sep 27]. Available from: http://www.cardiodx.com/
- Corus CAD product overview [Internet]. Redwood City (CA): CardioDx, Inc.; 2017. [cited 2017 Sep 27]. Available from: http://www.cardiodx.com/corus-cad/product-overview/
- The vision of CORUS CAD [Internet].2017. [cited 2017 Oct 10]. Available from: https://www.youtube.com/embed/9UqNjJevVDU?rel=0&autoplay=1 video, 5:37 min.
- Vargas J, Lima JA, Kraus WE, Douglas PS, Rosenberg S. Use of the Corus CAD Gene Expression Test for Assessment of Obstructive Coronary Artery Disease Likelihood in Symptomatic Non-Diabetic Patients. PLoS Curr [Internet]. 2013 Aug 26 [cited 2017 May 15];5. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3770834/?report=printable
- Clinician access portal [Internet]. Redwood City (CA): CardioDx, Inc.; 2017. [cited 2017 Oct 10].
- Lansky A, Elashoff MR, Ng V, McPherson J, Lazar D, Kraus WE, et al. A gender-specific blood-based gene expression score for assessing obstructive coronary artery disease in nondiabetic patients: results of the Personalized Risk Evaluation and Diagnosis in the Coronary Tree (PREDICT) trial. Am Heart J. 2012 Sep;164(3):320-6.
- [Internet]. Redwood City (CA): CardioDx, Inc. Corus CAD intended use; 2017 [cited 2017 Sep 27]. Available from: http://www.cardiodx.com/corus-cad-intended-use/
- Corus CAD (CardioDx, Inc.) gene expression testing for assessing risk of obstructive coronary artery disease. Plymouth Meeting (PA): ECRI Institute; 2017. (Genetic test product brief).
- Corus® CAD patient cost information [Internet]. Redwood City (CA): CardioDx, Inc.; 2015. [cited 2017 Oct 10]. Available from: http://www.cardiodx.com/assets/CARE-Patient-Program/Patient-Cost-Information.pdf
- Heart disease - heart health [Ottawa]. Ottawa: Public Health Agency of Canada; 2017. [cited 2017 Oct 20]. Available from: https://www.canada.ca/en/public-health/services/diseases/heart-disease-heart-health.html
- [Internet]. Ottawa: Public Health Agency of Canada. Tracking heart disease and stroke in Canada; 2009 [cited 2017 Sep 27]. Available from: https://www.canada.ca/content/dam/phac-aspc/migration/phac-aspc/publicat/2009/ cvd-avc/pdf/cvd-avs-2009-eng.pdf
- [Internet]. Ottawa: Public Health Agency of Canada. Health status of Canadians 2016: report of the Chief Public Health Officer - How are we unhealthy? - Cardiovascular disease; 2016 [cited 2017 Sep 27]. Available from: https://www.canada.ca/en/public-health/corporate/publications/chief-public-health-officer-reports-state-public-health-canada/2016-health-status-canadians/page-17-how-are-we-unhealthy-cardiovascular-disease.html
- Clarke JL, Ladapo JL, Monane M, Lansky A, Skoufalos A, Nash DB. The diagnosis of CAD in women: addressing the unmet need - a report from the national expert roundtable meeting. Popul Health Manag [Internet]. 2015 Apr [cited 2017 May 15];18(2):86-92. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4410448/pdf/pop.2015.0006.pdf
- Canadian Diabetes Association Clinical Practice Guidelines Expert Committee, Poirier P, Dufour R, Carpentier A, Larose E. Screening for the presence of coronary artery disease [Internet]. Toronto: Canadian Diabetes Association; 2013. [cited 2017 Nov 23]. Available from: http://guidelines.diabetes.ca/browse/chapter23
- Boden WE, O’Rourke RA, Teo KK, Hartigan PM, Maron DJ, Kostuk WJ, et al. Optimal medical therapy with or without PCI for stable coronary disease. N Engl J Med. 2007 Apr 12;356(15):1503-16.
- Ko DT, Tu JV, Austin PC, Wijeysundera HC, Samadashvili Z, Guo H, et al. Prevalence and extent of obstructive coronary artery disease among patients undergoing elective coronary catheterization in New York State and Ontario. JAMA. 2013 Jul 10;310(2):163-9.
- Rosenberg S, Elashoff MR, Beineke P, Daniels SE, Wingrove JA, Tingley WG, et al. Multicenter validation of the diagnostic accuracy of a blood-based gene expression test for assessing obstructive coronary artery disease in nondiabetic patients. Ann Intern Med [Internet]. 2010 Oct 5 [cited 2017 Aug 15];153(7):425-34. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3786733/pdf/nihms494017.pdf
- Thomas GS, Voros S, McPherson JA, Lansky AJ, Winn ME, Bateman TM, et al. A blood-based gene expression test for obstructive coronary artery disease tested in symptomatic nondiabetic patients referred for myocardial perfusion imaging the COMPASS study. Circ Cardiovasc Genet. 2013 Apr;6(2):154-62.
- McPherson JA, Davis K, Yau M, Beineke P, Rosenberg S, Monane M, et al. The clinical utility of gene expression testing on the diagnostic evaluation of patients presenting to the cardiologist with symptoms of suspected obstructive coronary artery disease: results from the IMPACT (Investigation of a Molecular Personalized Coronary Gene Expression Test on Cardiology Practice Pattern) trial. Crit Pathw Cardiol. 2013 Jun;12(2):37-42.
- Herman L, Froelich J, Kanelos D, St AR, Yau M, Rhees B, et al. Utility of a genomic-based, personalized medicine test in patients presenting with symptoms suggesting coronary artery disease. J Am Board Fam Med [Internet]. 2014 Mar [cited 2017 May 15];27(2):258-67. Available from: http://www.jabfm.org/content/27/2/258.full.pdf+html
- Ladapo JA, Lyons H, Yau M, Rich P, Newton D, Bruce-Mensah K, et al. Enhanced assessment of chest pain and related symptoms in the primary care setting through the use of a novel personalized medicine genomic test: results from a prospective registry study. Am J Med Qual. 2015 Jul;30(4):345- 52.
- Ladapo JA, Budoff M, Sharp D, Zapien M, Huang L, Maniet B, et al. Clinical Utility of a Precision Medicine Test Evaluating Outpatients with Suspected Obstructive Coronary Artery Disease. Am J Med. 2017 Apr;130(4):482.e11-7.
- Rosenberg S, Elashoff MR, Lieu HD, Brown BO, Kraus WE, Schwartz RS, et al. Whole blood gene expression testing for coronary artery disease in nondiabetic patients: major adverse cardiovascular events and interventions in the PREDICT trial. J Cardiovasc Transl Res [Internet]. 2012 Jun [cited 2017 May 15];5(3):366-74. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3349850/pdf/12265_2012_Article_9353.pdf
- McPherson JA, Kraus WE, Voros S, Topol EJ, Rhees B, Daniels SE, et al. A peripheral blood gene expression score for obstructive coronary artery disease is significantly associated with major adverse cardiovascular events and revascularizations in the predict trial. Circulation [Internet]. 2013 [cited 2017 May 15];128(22 Suppl 1). Available from: http://circ.ahajournals.org/content/128/Suppl_22/A16271
- Ladapo JA, Budoff MJ, Sharp D, Kuo JZ, Huang L, Maniet B, et al. Utility of a Precision Medicine Test in Elderly Adults with Symptoms Suggestive of Coronary Artery Disease. J Am Geriatr Soc [Internet]. 2017 Dec 6 [cited 2018 Feb 8];309-15. Available from: http://onlinelibrary.wiley.com/doi/10.1111/jgs.15215/epdf
- Ladapo JA, Herman L, Weiner BH, Rhees B, Castle L, Monane M, et al. Use of a blood test incorporating age, sex, and gene expression influences medical decision-making in the evaluation of women presenting with symptoms suggestive of obstructive coronary artery disease: summary results from two ambulatory care studies in primary care. Menopause. 2015 Nov;22(11):1224-30.
- Pokrywka G, Ladapo JA, Wright R, McLaughlin P, Maniet B, Sharp D, et al. The clinical utility of a blood test incorporating age, sex, and gene expression in the evaluation of women presenting with stable symptoms suggestive of obstructive coronary artery disease in a large primary care registry (PRESET): Subgroup analysis of the primary efficacy endpoint [abstract]. Menopause. 2015;22(12):1400.
- Ladapo JA, Budoff M, Sharp D, Zapien M, Huang L, Maniet B, et al. The clinical utility of a precision medicine blood test incorporating age, sex, and gene expression in the evaluation of 288 women presenting with stable symptoms suggestive of obstructive coronary artery disease: Subgroup analysis from the preset registry [abstract]. J Womens Health. 2016;25(4):A19.
- Conlin M, Herman L, Mouton M, Wilson L, Patel R, McPherson JA. The use of a personalized gene expression test to improve decision making in the evaluation of women with suspected coronary artery disease [abstract]. J Womens Health. 2013;22(3):7-8.
- Conlin MF, Mouton M, Herman LE, Yau M, Monane M, McPherson J, et al. The use of a personalized gene expression test to improve decision making in the evaluation of patients with suspected coronary artery disease. J Gen Intern Med. 2012;27 Suppl:S540-S541.
- Kline L, Burkle J, Hoffman DA, Littleford L, Ross L, Blanchard J, et al. Improved patterns of diagnostic management of patients using a personalized gene expression score among matched cohorts of patients presenting to the cardiologist with symptoms of suspected obstructive coronary artery disease: Results from the understanding clinician utility- cardiology trial [abstract]. Circulation: Cardiovascular Quality and Outcomes [Internet]. 2014 [cited 2017 May 15];7. Available from: http://circoutcomes.ahajournals.org/content/7/Suppl_1/A166
- Phelps CE, O’Sullivan AK, Ladapo JA, Weinstein MC, Leahy K, Douglas PS. Cost effectiveness of a gene expression score and myocardial perfusion imaging for diagnosis of coronary artery disease. Am Heart J. 2014 May;167(5):697-706.
- Hochheiser LI, Juusola JL, Monane M, Ladapo JA. Economic utility of a blood-based genomic test for the assessment of patients with symptoms suggestive of obstructive coronary artery disease. Popul Health Manag [Internet]. 2014 Oct [cited 2017 May 15];17(5):287-96. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4162448/pdf/pop.2013.0096.pdf
- McPherson JA, Yau M, Juusola JL, Monane M, Ladapo JA. Use of a blood-based gene expression score was associated with lower diagnostic testing costs in patients presenting to the cardiologist with symptoms suggestive of obstructive coronary artery disease: An economic analysis of the impact-card (investigation of a molecular personalized coronary gene expression test on cardiology practice pattern) trial [abstract]. Value Health. 2014;17(3):A122-A123.
- Herman L, Conlin M, Watson P, Froelich J, Kanelos D, St AR, et al. Improved patterns for advanced non-invasive diagnostic testing using a personalized gene expression score among patients presenting to primary care clinicians with symptoms of suspected obstructive coronary artery disease: Results from the impact-PCP (Investigation of a molecular personalized coronary gene expression test on primary care practice pattern) trial [abstract]. Circulation: Cardiovascular Quality and Outcomes [Internet]. 2013 [cited 2017 May 15];6(3 Suppl 1). Available from: http://circoutcomes.ahajournals.org/content/6/Suppl_1/A340
- Voros S, Elashoff MR, Wingrove JA, Budoff MJ, Thomas GS, Rosenberg S. A peripheral blood gene expression score is associated with atherosclerotic Plaque Burden and Stenosis by cardiovascular CT-angiography: results from the PREDICT and COMPASS studies. Atherosclerosis [Internet]. 2014 Mar;233(1):284-90.
- Joshi PH, Rinehart S, Vazquez G, Qian Z, Sharma A, Anderson H, et al. A peripheral blood gene expression score is associated with plaque volume and phenotype by intravascular ultrasound with radiofrequency backscatter analysis: results from the ATLANTA study. Cardiovasc Diagn Ther [Internet]. 2013 Mar [cited 2017 May 15];3(1):5-14. Available from: https://www.ncbi. nlm.nih.gov/pmc/articles/PMC3839219/pdf/cdt-03-01-005.pdf
- Daniels SE, Beineke P, Rhees B, McPherson JA, Kraus WE, Thomas GS, et al. Biological and analytical stability of a peripheral blood gene expression score for obstructive coronary artery disease in the PREDICT and COMPASS studies. J Cardiovasc Transl Res [Internet]. 2014 Oct;7(7):615-22. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4185104/pdf/12265_2014_Article_9583.pdf
- Filsoof DM, Safford RE, Newby K, Rosenberg S, Kontras DG, Baker A, et al. Impact of exercise stress testing on diagnostic gene expression in patients with obstructive and nonobstructive coronary artery disease. Am J Cardiol. 2015 May 15;115(10):1346-50.
- Voora D, Coles A, Lee KL, Hoffmann U, Wingrove JA, Rhees B, et al. An age- and sex-specific gene expression score is associated with revascularization and coronary artery disease: Insights from the Prospective Multicenter Imaging Study for Evaluation of Chest Pain (PROMISE) trial. Am Heart J. 2017 Feb;184:133-40.
- Jessee R, Peart E, Beineke P, Rosenberg S, Wingrove JA, Kraus WE, et al. Rheumatoid arthritis complicates noninvasive whole blood gene expression testing for coronary artery disease. Am Heart J. 2017 Oct;192:13-8.
- Zeller T, Blankenberg S. Blood-based gene expression tests: promises and limitations. Circ Cardiovasc Genet. 2013 Apr;6(2):139-40.
About This Document
Authors: Jeff Mason, Nina Frey.
Cite As: A gene expression test to assess the likelihood of obstructive coronary artery disease. Ottawa: CADTH; 2018 Mar. (CADTH issues in emerging health technologies; issue 170)
Acknowledgements: CADTH thanks the external reviewers who kindly provided comments on an earlier draft of this bulletin.
ISSN: 1488-6324 (English)
Disclaimer: The information in this document is intended to help Canadian health care decision-makers, health care professionals, health systems leaders, and policy- makers make well-informed decisions and thereby improve the quality of health care services. While patients and others may access this document, the document is made available for informational purposes only and no representations or warranties are made with respect to its fitness for any particular purpose. The information in this document should not be used as a substitute for professional medical advice or as a substitute for the application of clinical judgment in respect of the care of a particular patient or other professional judgment in any decision-making process. The Canadian Agency for Drugs and Technologies in Health (CADTH) does not endorse any information, drugs, therapies, treatments, products, processes, or services.
While care has been taken to ensure that the information prepared by CADTH in this document is accurate, complete, and up-to-date as at the applicable date the material was first published by CADTH, CADTH does not make any guarantees to that effect. CADTH does not guarantee and is not responsible for the quality, currency, propriety, accuracy, or reasonableness of any statements, information, or conclusions contained in any third-party materials used in preparing this document. The views and opinions of third parties published in this document do not necessarily state or reflect those of CADTH.
CADTH is not responsible for any errors, omissions, injury, loss, or damage arising from or relating to the use (or misuse) of any information, statements, or conclusions contained in or implied by the contents of this document or any of the source materials.
This document may contain links to third-party websites. CADTH does not have control over the content of such sites. Use of third-party sites is governed by the third-party website owners’ own terms and conditions set out for such sites. CADTH does not make any guarantee with respect to any information contained on such third-party sites and CADTH is not responsible for any injury, loss, or damage suffered as a result of using such third-party sites. CADTH has no responsibility for the collection, use, and disclosure of personal information by third-party sites.
Subject to the aforementioned limitations, the views expressed herein are those of CADTH and do not necessarily represent the views of Canada’s federal, provincial, or territorial governments or any third party supplier of information.
This document is prepared and intended for use in the context of the Canadian health care system. The use of this document outside of Canada is done so at the user’s own risk.
This disclaimer and any questions or matters of any nature arising from or relating to the content or use (or misuse) of this document will be governed by and interpreted in accordance with the laws of the Province of Ontario and the laws of Canada applicable therein, and all proceedings shall be subject to the exclusive jurisdiction of the courts of the Province of Ontario, Canada.
The copyright and other intellectual property rights in this document are owned by CADTH and its licensors. These rights are protected by the Canadian Copyright Act and other national and international laws and agreements. Users are permitted to make copies of this document for non-commercial purposes only, provided it is not modified when reproduced and appropriate credit is given to CADTH and its licensors.
About CADTH: CADTH is an independent, not-for-profit organization responsible for providing Canada’s health care decision-makers with objective evidence to help make
informed decisions about the optimal use of drugs, medical devices, diagnostics, and procedures in our health care system. Funding: CADTH receives funding from Canada’s federal, provincial, and territorial governments, with the exception of Quebec. Contact firstname.lastname@example.org with inquiries about this notice or legal matters relating to CADTH services.