Routine Versus As-Needed Stress Testing in Asymptomatic Patients With High-Risk Coronary Calcium (SMART-EXAM)

SMart Angioplasty Research Team-Pragmatic Randomized Trial for Comparing Routine Versus As-Needed EXercise or Pharmacologic Stress Testing in Asymptomatic Patients With High-Risk Coronary CalciuM (SMART-EXAM)

The purpose of the SMART-EXAM (SMart Angioplasty Research Team-Pragmatic Randomized Trial for Comparing Routine versus As-Needed EXercise or Pharmacologic Stress Testing in Asymptomatic Patients with High-Risk Coronary CalciuM) trial is to compare the major adverse cardiovascular events between routine stress testing and as-needed stress testing in asymptomatic patients with high-risk coronary calcium (Agatston Score ≥ 400) without proven ASCVD.

Study Overview

• Status: Not yet recruiting
• Conditions: Coronary Atherosclerosis Due to Calcified Coronary Lesion
• Intervention / Treatment: Diagnostic test: Non-invasive stress test; Diagnostic test: Medical treatment without further testing

Detailed Description

The coronary artery calcium (CAC) scan, a marker of subclinical coronary atherosclerosis, has become popular for individuals at risk for atherosclerotic cardiovascular disease. CAC is strongly associated with atherosclerotic burden and predicts coronary heart disease events and mortality, regardless of their age, sex, race, or atherosclerotic cardiovascular disease (ASCVD) risk. Furthermore, the progression of CAC is associated with an increased risk for future hard and total coronary heart disease events. The use of CAC scoring was associated with significant improvements in the reclassification and discrimination of incident ASCVD. Nevertheless, the current guidelines recommend CAC measurement for selected cases only with borderline or intermediate risk of ASCVD. However, in real-world practice, CAC testing is increasingly being promoted to the public as a means of self-assessment of cardiovascular risk and is widely being used regardless of ASCVD risk.

Non-invasive stress testing is often recommended to exclude potentially dangerous coronary artery disease. However, stress testing in asymptomatic individuals has low sensitivity and specificity.9 Although the 2019 Primary Prevention of Cardiovascular Disease Guidelines do not comment on functional or invasive testing in asymptomatic individuals with a high CAC score, the 2009 Appropriate Use Criteria for Cardiac Radionuclide Imaging report gives a level A recommendation for obtaining a stress test in asymptomatic individuals with CAC score ≥400.10 In addition, the 2013 update of the 2009 document also considers stress imaging appropriate for patients with CAC score >100. However, there have been no large randomized controlled trials or observational studies that have evaluated the utility of functional or invasive testing in asymptomatic individuals free of ASCVD with high CAC scores. Theoretically, early detection and revascularization of ischemia producing lesions in asymptomatic patients with high-risk coronary calcification without proven ASCVD might reduce the future risk of major adverse cardiovascular events.

• Study Type: Interventional
• Enrollment (Anticipated): 3000
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ki Hong Choi; Phone Number: 82-2-3410-6653; Email: cardiokh@gmail.com
• Study Contact Backup: Name: Seung-Hyuk Choi, MD; Phone Number: 82-2-3410-3419; Email: sh1214.choi@samsung.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subject must be at least 19 years of age. ② Asymptomatic patients with high-risk coronary calcium (Agatston Score ≥ 400)

Exclusion Criteria:

• Documentation of objective evidence of inducible ischemia before enrollment

  • Presence of significant coronary artery stenosis (≥ 70% diameter stenosis) confirmed by coronary angiography or coronary computed tomography angiography before enrollment

    • History of coronary revascularization procedure ④ Pregnancy or breast feeding ⑤ Non-cardiac co-morbid conditions are present with life expectancy <1 year or that may result in protocol non-compliance (per site investigator's medical judgment) ⑥ Unwillingness or inability to comply with the procedures described in this protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Routine stress testing; In this group, the preselected functional stress testing (exercise electrocardiography, stress echocardiography, nuclear imaging, or stress cardiac magnetic resonance imaging) will be performed within three months (± 2 months) according to the practice pattern of each participating center.	Diagnostic test: Non-invasive stress test; Nuclear imaging, stress echocardiography, exercise electrocardiography, stress cardiac magnetic resonance imaging
Active Comparator: As-needed stress testing; In this group, optimal medical treatment will be performed by current guidelines without further testing. A stress test will be performed only when new symptoms (exertional chest pain or dyspnea) occur that may clinically suggest significant coronary artery disease.	Diagnostic test: Medical treatment without further testing; Optimal medical treatment for primary prevention.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of major adverse cardiovascular events	a composite of death from cardiovascular causes, myocardial infarction, unplanned hospitalization leading to an urgent revascularization procedure, or heart failure hospitalization	up to 4.5 years of median follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
cardiovascular death	death from cardiovascular causes	up to 4.5 years of median follow-up
myocardial infarction	myocardial infarction	up to 4.5 years of median follow-up
unplanned hospitalization leading to an urgent revascularization procedure	unplanned hospitalization leading to an urgent revascularization procedure	up to 4.5 years of median follow-up
heart failure hospitalization	heart failure hospitalization	up to 4.5 years of median follow-up
all-cause death	death from any causes	up to 4.5 years of median follow-up
a composite of death from cardiovascular cause or myocardial infarction	a composite of death from cardiovascular cause or myocardial infarction	up to 4.5 years of median follow-up
any hospitalization	any hospitalization	up to 4.5 years of median follow-up
performing revascularization procedure	performing revascularization procedure	up to 4.5 years of median follow-up
performing invasive coronary angiography procedure	performing invasive coronary angiography procedure	up to 4.5 years of median follow-up
stroke	stroke	up to 4.5 years of median follow-up
bleeding	Bleeding Academic Research Consortium type 2-5	up to 4.5 years of median follow-up
total medical cost	total medical cost	up to 4.5 years of median follow-up

Collaborators and Investigators

• Sponsor: Samsung Medical Center
• Investigators: Principal Investigator: Seung-Hyuk Choi, MD, Samsung Medical Center

Study record dates

Study Major Dates

• Study Start (Anticipated): May 1, 2023
• Primary Completion (Anticipated): June 30, 2029
• Study Completion (Anticipated): December 31, 2029

Study Registration Dates

• First Submitted: March 21, 2023
• First Submitted That Met QC Criteria: March 21, 2023
• First Posted (Actual): April 3, 2023

Study Record Updates

• Last Update Posted (Actual): April 3, 2023
• Last Update Submitted That Met QC Criteria: March 21, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Coronary calcification; Non-invasive stress test; Agatston score
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Disease; Coronary Artery Disease; Myocardial Ischemia; Atherosclerosis
• Other Study ID Numbers: SMART-EXAM

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No