PET Stress Test vs CAC Scan for Coronary Artery Disease

(ACCURATE Trial)

Overseen By Patti Spencer

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Intermountain Health Care, Inc.

Disqualifiers: Prior CAD, Heart transplant, Severe valve disease, Decompensated heart failure, others

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

Compensation: Varies

Number of Visits: 1

2500 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The cost of medical care in the United States far exceeds that of all other advanced economies and continues to accelerate at a rate unacceptable to our society, due primarily to the high costs of new imaging technologies and novel drugs (1). Cardiac positron emission tomography (PET) imaging is a powerful new modality for the non-invasive detection of provocable coronary ischemia in patients with low to intermediate-risk chest pain or its equivalent. Intermountain Medical Center (IMC) is performing approximately 6000 clinical cardiac PET scans annually. However, cardiac PET scans are expensive (i.e., billed at \>$5,000/scan, average receivable revenue $1500-$2000/scan). Coronary artery calcium (CAC) is a sensitive marker of coronary atherosclerosis. A CAC scan (CACS), performed by multislice computed tomography (CT), is a relatively inexpensive (\~$70-$150/scan), low-radiation dose test that marks the presence of coronary atherosclerotic plaque. The absence of CAC has been shown to be associated with very low coronary risk. ACCURATE will test whether a CAC-first strategy (i.e., risk stratification, when CAC ≤ 1, to medical management or to cardiac PET stress testing), performed routinely in symptomatic patients presenting for evaluation of possible coronary artery disease (CAD) prior to the cardiac PET stress test, can be used as a gatekeeper for progression to the expensive rubidium-PET stress (regadenoson) perfusion scan and be a major cost-saver without adversely affecting patient care or outcomes. Routinely, qualifying patients undergo CACS when they present for evaluation of possible but unknown CAD status and are referred for cardiac PET stress testing. In ACCURATE, those with CACS≤1 will then be consented and randomized to either a cardiac PET stress test strategy or a non-PET-driven medical care strategy. Subjects randomized to the cardiac PET stress test strategy will receive appropriate subsequent care depending on the outcome of the cardiac PET scan (i.e., depending on whether ischemia is present or not). Subjects randomized to the CAC-only arm will receive appropriate non-PET driven medical clinical management and follow-up. All participating subjects' electronic medical records will be reviewed indefinitely for clinical outcomes. Initial outcomes will be reported at 1-year, 2-years, and 5-years, with future analyses to be determined by the study investigators. The objective of this study is to test the hypothesis that PET stress test strategy will results in a decreasing in major adverse cardiac endpoint without exceeding $100,000 per quality-adjusted life year compared to a CAC-first strategy for screening suspected/possible coronary artery disease.

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's best to discuss this with the study team or your doctor.

Is the PET Stress Test using regadenoson safe for humans?

Regadenoson, used in PET Stress Tests, is generally safe and well-tolerated by patients. It is a newer agent that is better tolerated than adenosine, another common stress agent, and is used to help diagnose coronary artery disease. ^{1 2 3 4 5}

How does the PET Stress Test differ from other treatments for coronary artery disease?

The PET Stress Test uses pharmacological stress agents like regadenoson, which is a selective coronary vasodilator, to assess blood flow in the heart, making it a noninvasive and patient-friendly alternative to traditional exercise stress tests. This approach is unique because it can be used for patients who cannot perform physical exercise, and regadenoson is better tolerated compared to other agents like adenosine. ^{1 2 4 6 7}

What data supports the effectiveness of the PET Stress Test for Coronary Artery Disease?

Research shows that regadenoson, a drug used in PET stress tests, is safe and can help guide treatment decisions in patients with heart conditions, like those undergoing valve replacement. Additionally, PET stress tests using regadenoson can effectively identify heart issues, which may help in managing coronary artery disease. ^{1 3 8 9 10}

Who Is on the Research Team?

Jeffrey Anderson

Principal Investigator

Intermountain Medical Center

Kirk U Knowlton, MD

Principal Investigator

Intermountain Medical Center

Are You a Good Fit for This Trial?

This trial is for men and women over 50 who may have coronary artery disease, as suggested by chest pain or similar symptoms. They must understand and agree to the study's process. People with known heart conditions, a high calcium score from previous tests, or certain other health issues can't join.

Inclusion Criteria

Ability to understand and sign a written informed consent form, which must be obtained prior to initiation of any study procedures

I am scheduled for a cardiac PET scan to check for heart-related chest pain.

I am 50 years old or older.

Exclusion Criteria

I am scheduled for a heart PET/CT scan before my major non-chest surgery.

Your calcium score from your most recent heart check is higher than 1.

Your doctor thinks you have less than a year to live.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Initial Evaluation

Participants undergo Coronary Artery Calcium (CAC) scan to assess coronary atherosclerosis

1 week

1 visit (in-person)

Randomization and Treatment

Participants are randomized to either a cardiac PET stress test strategy or a non-PET-driven medical care strategy

Varies based on treatment arm

Follow-up

Participants are monitored for major adverse cardiac endpoints and cost-effectiveness

5 years

Annual reviews

What Are the Treatments Tested in This Trial?

Interventions

• Non-PET Medical Management
• PET Stress Test

Trial Overview The study compares two approaches in patients suspected of having coronary artery disease: one group gets a PET stress test directly while the other follows a 'calcium-first' strategy which could lead to medical management without PET if their calcium levels are low.

How Is the Trial Designed?

Group I: Management without stress-imaging Experimental Treatment 1 Intervention

Subjects randomized to the CAC-only arm will receive appropriate non-PET driven medical clinical management and follow-up.

Group II: Cardiac PET stress testing and test-dependent management Experimental Treatment 1 Intervention

Subjects randomized to the cardiac PET stress test strategy will receive appropriate subsequent care depending on the outcome of the cardiac PET scan (i.e., depending on whether ischemia is present or not).

Who Is Running the Clinical Trial?

Intermountain Health Care, Inc.

Lead Sponsor

Trials

142

Recruited

1,965,000+

Published Research Related to This Trial

Stress PET using regadenoson is safe for patients with severe aortic stenosis, with no major adverse events reported during the study of 50 patients.

The PET results effectively guided revascularization decisions, with 44% of patients undergoing revascularization targeting areas of the heart that were at risk, as identified by the PET scan.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stress positron emission tomography is safe and can guide coronary revascularization in high-risk patients being considered for transcatheter aortic valve replacement. Cremer, PC., Khalaf, S., Lou, J., et al.[2021]

This study is the first multicenter, multivendor comparison of regadenoson-stress myocardial CT perfusion (CTP) with SPECT, involving approximately 25 sites and various CT scanner models, which aims to assess the effectiveness of CTP in detecting myocardial ischemia in patients with known or suspected coronary artery disease.

The primary goal is to determine if CTP can match or exceed the agreement rate of SPECT for detecting ischemia, with a non-inferiority threshold set to ensure that CTP is at least as effective as SPECT in identifying heart issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regadenoson-stress myocardial CT perfusion and single-photon emission CT: rationale, design, and acquisition methods of a prospective, multicenter, multivendor comparison. Cury, RC., Kitt, TM., Feaheny, K., et al.[2015]

In a study of 105 patients with suspected coronary artery disease (CAD), 82Rb PET/CT imaging effectively identified multi-vessel disease (MVD) with a high accuracy (ROC AUC of 83% for asynchrony scores).

The study also demonstrated that regional asynchrony measurements were crucial in detecting individual arteries with severe stenosis (≥70%), showing an ROC AUC of 81%, highlighting the importance of asynchrony in assessing CAD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relationship of 82Rb PET territorial myocardial asynchrony to arterial stenosis. Van Tosh, A., Votaw, JR., David Cooke, C., et al.[2021]

In a study involving 32 subjects, regadenoson was found to produce similar imaging results to dipyridamole for (82)RbCl PET scans, indicating its effectiveness in assessing cardiac perfusion and function.

Both visual assessments and quantitative measurements showed high correlation between regadenoson and dipyridamole, suggesting that regadenoson can be a suitable alternative due to its fixed dosing and favorable side effect profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regadenoson pharmacologic rubidium-82 PET: a comparison of quantitative perfusion and function to dipyridamole. Cullom, SJ., Case, JA., Courter, SA., et al.[2022]

In a study of 90 patients undergoing myocardial perfusion PET/CT, those stressed with regadenoson exhibited significantly lower motion scores compared to those stressed with adenosine, indicating better image quality and accuracy.

The type of motion observed was more likely to be non-returning in patients receiving adenosine, suggesting that the choice of pharmacological stressor can greatly influence patient motion and the resulting imaging outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of pharmacological stress agent on patient motion during rubidium-82 myocardial perfusion PET/CT. Memmott, MJ., Tonge, CM., Saint, KJ., et al.[2019]

Regadenoson is becoming the preferred pharmacological stressor for noninvasive functional imaging in diagnosing coronary artery disease (CAD), as it effectively induces hypoperfusion in patients with flow-limiting coronary stenosis.

The article reviews regadenoson's pharmacological properties, stress protocols, and highlights its efficacy and safety, emphasizing the importance for clinicians to understand its use in CAD management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regadenoson stress for myocardial perfusion imaging. Reyes, E.[2015]

Regadenoson, a newer selective adenosine receptor agonist, is as effective as traditional vasodilators like adenosine for detecting ischemia in stress perfusion studies, while being better tolerated by patients.

With over 7 million stress perfusion studies performed annually in the U.S., the use of vasodilator testing, including regadenoson, is crucial for noninvasive risk stratification in managing coronary artery disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current advances in vasodilator pharmacological stress perfusion imaging. Druz, RS.[2017]

Regadenoson, a selective A(2A) receptor agonist, significantly increased coronary blood flow in dogs with mild-to-moderate coronary stenosis, demonstrating its potential as an effective vasodilator during myocardial contrast echocardiography.

The study found that regadenoson did not cause any arrhythmias and allowed for the detection of perfusion defects for up to 10 minutes after administration, indicating its safety and efficacy in identifying significant coronary artery blockages.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Detection of coronary stenosis with myocardial contrast echocardiography using regadenoson, a selective adenosine A2A receptor agonist. Le, DE., Bragadeesh, T., Zhao, Y., et al.[2016]

In a study of 200 patients undergoing single photon emission computed tomography (SPECT) for coronary artery disease, eliminating the rest study rarely changed the interpretation of normal stress images, suggesting that a single stress test could be sufficient for diagnosis.

The findings indicate that rest studies are primarily beneficial for patients with abnormal or unclear stress images, which could lead to cost savings in nuclear procedures within managed health care systems.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A cost-effective sestamibi protocol in the managed health care era. Milan, E., Giubbini, R., Gioia, G., et al.[2019]

The noninvasive pacemaker stress echocardiography (PASE) test was found to be safe and effective for diagnosing coronary artery disease (CAD) in a study of 46 patients with permanent pacemakers, showing a sensitivity of 70% and specificity of 90%.

PASE demonstrated improved diagnostic accuracy when considering abnormal wall motion at rest, achieving a sensitivity of 85% and specificity of 84%, making it a promising alternative to traditional stress tests for patients with CAD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Noninvasive pacemaker stress echocardiography for diagnosis of coronary artery disease: a multicenter study. Picano, E., Alaimo, A., Chubuchny, V., et al.[2019]

Citations

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

Stress positron emission tomography is safe and can guide coronary revascularization in high-risk patients being considered for transcatheter aortic valve replacement. [2021]

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

Regadenoson-stress myocardial CT perfusion and single-photon emission CT: rationale, design, and acquisition methods of a prospective, multicenter, multivendor comparison. [2015]

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

Relationship of 82Rb PET territorial myocardial asynchrony to arterial stenosis. [2021]

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

Regadenoson pharmacologic rubidium-82 PET: a comparison of quantitative perfusion and function to dipyridamole. [2022]

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

Impact of pharmacological stress agent on patient motion during rubidium-82 myocardial perfusion PET/CT. [2019]

6. England pubmed.ncbi.nlm.nih.gov

Regadenoson stress for myocardial perfusion imaging. [2015]

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

Current advances in vasodilator pharmacological stress perfusion imaging. [2017]

8. England pubmed.ncbi.nlm.nih.gov

Detection of coronary stenosis with myocardial contrast echocardiography using regadenoson, a selective adenosine A2A receptor agonist. [2016]

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

A cost-effective sestamibi protocol in the managed health care era. [2019]

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

Noninvasive pacemaker stress echocardiography for diagnosis of coronary artery disease: a multicenter study. [2019]