Coronary Artery Disease, Myocardial Ischemia
Conditions
Brief summary
Not infrequently, a physician is faced with uncertainty regarding the ability of a patient to perform adequate exercise in the noninvasive evaluation of known or suspected coronary artery disease (CAD) by the use of radionuclide stress myocardial perfusion imaging. In selected patients, protocols that combine exercise (either low-level or symptom-limited) with vasodilator stress agents have been found to be safe and effective in both identification of the presence and severity of CAD as well as risk stratification for adverse cardiac outcome. However, currently utilized combined stress protocols have drawbacks. Further refinement of combined stress protocols would potentially lead to more appropriate stress protocol selection for patients while enhancing laboratory efficiency. The purpose of this prospective, randomized study will be to evaluate the relative merits of combining regadenoson with symptom-limited exercise in patients clinically-referred for vasodilator-exercise stress myocardial perfusion imaging for the assessment of known or suspected CAD. It is hypothesized that combining regadenoson with symptom-limited exercise is a safe and feasible stress testing modality which is non-inferior to that which combines symptom-limited exercise with dipyridamole.
Interventions
DRUGRegadenoson
Regadenoson (0.4mg/5 mL) injection during symptom-limited exercise with technetium-99m SPECT myocardial perfusion imaging
OTHERSymptom-limited exercise
Dipyridamole (0.56 mg/kg) over 4 minutes followed by symptom-limited exercise with technetium-99m SPECT myocardial perfusion imaging
Sponsors
Astellas Pharma Inc
Hartford Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
30 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Males and non-pregnant, non-nursing females clinically referred for vasodilator stress myocardial perfusion imaging with the addition of exercise * Age \>=30 years
Exclusion criteria
* Extremely limited functional capacity * Age \<30 years * Unable or unwilling to provide informed consent * Pregnant or nursing females * Current use of methylxanthines within 12 hours of testing * Current use of dipyridamole or aminophylline within 48 hours of testing * Uncontrolled hypertension (\>200 mmHg systolic/\>120 mmHg diastolic) * Known hypertrophic cardiomyopathy with obstruction or severe aortic stenosis * Decompensated congestive heart failure * History of sick sinus syndrome or \> first degree atrioventricular block in the absence of a functioning pacemaker * Asthma or other bronchospastic reactive airway disease * History of percutaneous coronary intervention or coronary artery bypass grafting, or documented history of acute myocardial infarction or unstable angina within one week of testing * Patients at risk for hypotensive reaction to regadenoson
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Major Adverse Events or Side Effects Graded Severe on Symptom Questionnaire | 24 hours | Number of participants with any side effect (flushing, shortness of breath, headache, chest discomfort, dizziness, nausea, or abdominal pain) requiring specific treatment or graded as severe by the patient; or any death, myocardial infarction, or unplanned hospitalization. Note that 2 patients allocated to exercise-vasodilator stress did not complete symptom questionnaires and are therefore excluded from analysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Myocardial Perfusion Image Quality | 0 hours | Single photon emission computed tomography myocardial perfusion acquisition and image processing was performed in accordance with American Society of Nuclear Cardiology guidelines. All images were interpreted by consensus read of three investigators blinded to stress test protocol and results. Overall perfusion and gated image quality were described as excellent (no artifacts interfering with myocardial perfusion interpretation), good, fair, or poor (artifact requiring reprocessing or repeat imaging of the patient to allow for diagnostic interpretation). |
Countries
United States
Participant flow
Recruitment details
Recruitment took place in the Hartford Hospital Nuclear Cardiology Laboratory from January 2010 and February 2012.
Pre-assignment details
At the onset of the study, only subjects with scores greater than or equal to 9.95 were randomized. After the first 96 patients had been screened and 55 randomized with no adverse events in the study group, this restriction was removed.
Participants by arm
| Arm | Count |
|---|---|
| Vasodilator-exercise Stress Four-minute infusion of dipyridamole (0.56 mg/kg) followed by symptom-limited exercise. | 44 |
| Exercise-vasodilator Stress Symptom-limited exercise followed by a bolus intravenous injection of regadenoson (0.4 mg/5 mL) only in patients failing to achieve a standard clinical endpoint | 96 |
| Total | 140 |
Baseline characteristics
| Characteristic | Vasodilator-exercise Stress | Exercise-vasodilator Stress | Total |
|---|---|---|---|
| Age Continuous | 59 years STANDARD_DEVIATION 13 | 63 years STANDARD_DEVIATION 11 | 62 years STANDARD_DEVIATION 12 |
| Indication for Stress Testing Arrhythmia | 1 participants | 7 participants | 8 participants |
| Indication for Stress Testing Chest Pain | 36 participants | 71 participants | 107 participants |
| Indication for Stress Testing Dyspnea | 4 participants | 8 participants | 12 participants |
| Indication for Stress Testing Other | 1 participants | 6 participants | 7 participants |
| Indication for Stress Testing Syncope or Near-Syncope | 2 participants | 4 participants | 6 participants |
| Known Coronary Artery Disease Any known coronary disease | 15 participants | 29 participants | 44 participants |
| Known Coronary Artery Disease No known coronary disease | 29 participants | 67 participants | 96 participants |
| Race/Ethnicity, Customized Black | 8 Participants | 19 Participants | 27 Participants |
| Race/Ethnicity, Customized Caucasian | 21 Participants | 50 Participants | 71 Participants |
| Race/Ethnicity, Customized Hispanic | 13 Participants | 24 Participants | 37 Participants |
| Race/Ethnicity, Customized Other | 2 Participants | 3 Participants | 5 Participants |
| Sex: Female, Male Female | 23 Participants | 44 Participants | 67 Participants |
| Sex: Female, Male Male | 21 Participants | 52 Participants | 73 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 11 / 44 | 14 / 94 |
| serious Total, serious adverse events | 2 / 44 | 2 / 96 |
Outcome results
Primary
Number of Participants With Major Adverse Events or Side Effects Graded Severe on Symptom Questionnaire
Number of participants with any side effect (flushing, shortness of breath, headache, chest discomfort, dizziness, nausea, or abdominal pain) requiring specific treatment or graded as severe by the patient; or any death, myocardial infarction, or unplanned hospitalization. Note that 2 patients allocated to exercise-vasodilator stress did not complete symptom questionnaires and are therefore excluded from analysis.
Time frame: 24 hours
Population: Note that 2 patients allocated to exercise-vasodilator stress did not complete symptom questionnaires and are therefore excluded from analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vasodilator-exercise Stress | Number of Participants With Major Adverse Events or Side Effects Graded Severe on Symptom Questionnaire | 11 participants |
| Exercise-vasodilator Stress | Number of Participants With Major Adverse Events or Side Effects Graded Severe on Symptom Questionnaire | 15 participants |
Secondary
Myocardial Perfusion Image Quality
Single photon emission computed tomography myocardial perfusion acquisition and image processing was performed in accordance with American Society of Nuclear Cardiology guidelines. All images were interpreted by consensus read of three investigators blinded to stress test protocol and results. Overall perfusion and gated image quality were described as excellent (no artifacts interfering with myocardial perfusion interpretation), good, fair, or poor (artifact requiring reprocessing or repeat imaging of the patient to allow for diagnostic interpretation).
Time frame: 0 hours
Population: Note that images were unavailable in one vasodilator-exercise patient because of urgent catheterization after stress test without imaging and one exercise-vasodilator patient for technical reasons.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Vasodilator-exercise Stress | Myocardial Perfusion Image Quality | Excellent | 13 participants |
| Vasodilator-exercise Stress | Myocardial Perfusion Image Quality | Good | 25 participants |
| Vasodilator-exercise Stress | Myocardial Perfusion Image Quality | Fair | 5 participants |
| Vasodilator-exercise Stress | Myocardial Perfusion Image Quality | Poor | 0 participants |
| Exercise-vasodilator Stress | Myocardial Perfusion Image Quality | Poor | 0 participants |
| Exercise-vasodilator Stress | Myocardial Perfusion Image Quality | Excellent | 33 participants |
| Exercise-vasodilator Stress | Myocardial Perfusion Image Quality | Fair | 7 participants |
| Exercise-vasodilator Stress | Myocardial Perfusion Image Quality | Good | 55 participants |