Coronary Artery Disease, Myocardial Infarction
Conditions
Brief summary
This is a multi-centre observational study. It will make use of the positron emission tomography (PET) tracer 18F-sodium fluoride (18F-NaF) as a marker of coronary plaque vulnerability to detect culprit and non-culprit unstable coronary plaques in patients with recent myocardial infarctions. The investigators will then perform long-term follow-up of these patients to determine the prognostic significance of coronary 18F-NaF uptake
Detailed description
The investigators intend to recruit 700 patients hospitalised with myocardial infarction and proven multivessel coronary artery disease. All patients will undergo a combined CT coronary angiogram (CTCA) and PET scan using 18F-NaF as a tracer. Patients will then have clinical follow-up before undergoing a repeat CTCA at 2 years to assess progression of coronary disease. Clinical review of all patients will continue until study completion (given 2 years of recruitment this is likely to last 4 years) and following this the investigators will continue to monitor for further cardiovascular events via review of patient electronic health records for a further 5 years.
Interventions
None listed
Sponsors
NHS Lothian
Oxford University Hospitals NHS Trust
Manchester University NHS Foundation Trust
NHS Grampian
Wellcome Trust
University of Edinburgh
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients aged ≥50 years with recent (\<21 days) type 1 myocardial infarction and angiographically proven multi-vessel coronary artery disease defined as at least two major epicardial vessels with any combination of either (a) \>50% luminal stenosis, or (b) previous revascularization (percutaneous coronary intervention or coronary artery bypass graft surgery). 2. Provision of informed consent prior to any study specific procedures
Exclusion criteria
1. Inability or unwilling to give informed consent 2. Women who are pregnant, breastfeeding or of child-bearing potential (women who have experienced menarche, are pre-menopausal and have not been sterilised) will not be enrolled into the trial 3. Major intercurrent illness with life expectancy \<2 year 4. Renal dysfunction (estimated glomerular filtration rate ≤30 mL/min/1.73 m2) 5. Contraindication to iodinated contrast agent, positron emission tomography or computed tomography 6. Atrial fibrillation 7. Previous recruitment into the trial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cardiac Death, Non-fatal Recurrent Myocardial Infarction or Unscheduled Coronary Revascularisation | 2 years | To determine whether coronary 18F-fluoride uptake is associated with major adverse cardiac events in patients with multi-vessel coronary artery disease and recent myocardial infarction. Participants were followed up by site investigators until the last recruited patient had completed their 2-year follow-up visit. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| All Cause Death | 2 years | All cause death. Participants were followed up by site investigators until the last recruited patient had completed their 2-year follow-up visit. |
| Each Individual Component End-point of the Composite End-point of Major Adverse Cardiac Event | 2 years | Cardiac death, Nonfatal myocardial infarction, Unscheduled coronary revascularization |
Countries
United Kingdom
Participant flow
Recruitment details
Recruitment start date- September 2015 Recruitment end date - February 2020 The study was conducted in 9 centres across 4 countries (Scotland, England, United States and Australia) \[Note groups combined in below as participants only allocated to group after PET CT Scan analysed. Unable to report on reason not completed separately. as scan not complete at this point\]
Pre-assignment details
After consent 283 participants were excluded reasons below: Changed mind (n=142) Unable to scan within protocol window (n=82) Health subsequently deteriorated precluding inclusion (n=22) Unable to contact patient (n=19) Ineligible (n=10) Deceased (n=6) Clinician/investigator decision (n=2) 6 Participants attended baseline but did not complete the PET-CT Scan- were not allocated an arm. Reasons below: Claustrophobia (n=3) Panic attack (n=1) Anxious (n=1) Scanner malfunction (n=1)
Participants by arm
| Arm | Count |
|---|---|
| Low Coronary Atherosclerotic Plaque Activity Low coronary atherosclerotic plaque activity | 283 |
| High Coronary Atherosclerotic Plaque Activity High coronary atherosclerotic plaque activity | 421 |
| Total | 704 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Unable to analyse PET scan | 2 |
Baseline characteristics
| Characteristic | Low Coronary Atherosclerotic Plaque Activity | High Coronary Atherosclerotic Plaque Activity | Total |
|---|---|---|---|
| Age, Continuous | 61.8 years STANDARD_DEVIATION 7.4 | 65.1 years STANDARD_DEVIATION 8.4 | 63.8 years STANDARD_DEVIATION 8.2 |
| Body Mass index | 28.6 kg/m2 STANDARD_DEVIATION 4.7 | 28.1 kg/m2 STANDARD_DEVIATION 4.2 | 28.3 kg/m2 STANDARD_DEVIATION 4.4 |
| Cerebrovascular disease | 10 Participants | 23 Participants | 33 Participants |
| Coronary artery bypass graft surgery | 12 Participants | 19 Participants | 31 Participants |
| Coronary artery disease | 41 Participants | 98 Participants | 139 Participants |
| Diabetes | 40 Participants | 78 Participants | 118 Participants |
| Electrocardiography findings Missing data points | 0 Participants | 2 Participants | 2 Participants |
| Electrocardiography findings Non-ST-segment elevation myocardial infarction | 94 Participants | 145 Participants | 239 Participants |
| Electrocardiography findings ST-segment elevation myocardial infarction | 189 Participants | 274 Participants | 463 Participants |
| GRACE score | 113 scores on a scale STANDARD_DEVIATION 22 | 121 scores on a scale STANDARD_DEVIATION 26 | 118 scores on a scale STANDARD_DEVIATION 25 |
| Hypercholesterolemia | 162 Participants | 236 Participants | 398 Participants |
| Hypertension | 119 Participants | 232 Participants | 351 Participants |
| Medication ACE inhibitor or ARB No | 33 Participants | 48 Participants | 81 Participants |
| Medication ACE inhibitor or ARB Yes | 250 Participants | 373 Participants | 623 Participants |
| Medication Anticoagulant therapy No | 266 Participants | 396 Participants | 662 Participants |
| Medication Anticoagulant therapy Yes | 17 Participants | 25 Participants | 42 Participants |
| Medication Aspirin No | 15 Participants | 16 Participants | 31 Participants |
| Medication Aspirin Yes | 268 Participants | 405 Participants | 673 Participants |
| Medication Calcium-channel antagonist No | 264 Participants | 376 Participants | 640 Participants |
| Medication Calcium-channel antagonist Yes | 19 Participants | 45 Participants | 64 Participants |
| Medication Mineralocorticoid receptor antagonist No | 262 Participants | 400 Participants | 662 Participants |
| Medication Mineralocorticoid receptor antagonist Yes | 21 Participants | 21 Participants | 42 Participants |
| Medication Nitrate No | 125 Participants | 195 Participants | 320 Participants |
| Medication Nitrate Yes | 158 Participants | 226 Participants | 384 Participants |
| Medication Other antianginal therapy No | 275 Participants | 407 Participants | 682 Participants |
| Medication Other antianginal therapy Yes | 8 Participants | 14 Participants | 22 Participants |
| Medication Other diuretic therapy No | 261 Participants | 389 Participants | 650 Participants |
| Medication Other diuretic therapy Yes | 22 Participants | 32 Participants | 54 Participants |
| Medication P2Y12 receptor antagonist No | 4 Participants | 12 Participants | 16 Participants |
| Medication P2Y12 receptor antagonist Yes | 279 Participants | 409 Participants | 688 Participants |
| Medication Statin No | 23 Participants | 28 Participants | 51 Participants |
| Medication Statin Yes | 260 Participants | 393 Participants | 653 Participants |
| Medication β-Adrenergic receptor antagonist No | 50 Participants | 81 Participants | 131 Participants |
| Medication β-Adrenergic receptor antagonist Yes | 233 Participants | 340 Participants | 573 Participants |
| Myocardial infarction | 36 Participants | 66 Participants | 102 Participants |
| Percutaneous coronary intervention | 28 Participants | 404 Participants | 671 Participants |
| Peripheral vascular disease | 12 Participants | 9 Participants | 21 Participants |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Severity of obstructive coronary artery disease 1 Vessel | 12 Participants | 16 Participants | 28 Participants |
| Severity of obstructive coronary artery disease 2 Vessels | 163 Participants | 224 Participants | 387 Participants |
| Severity of obstructive coronary artery disease 3 Vessels | 90 Participants | 149 Participants | 239 Participants |
| Severity of obstructive coronary artery disease Left main stem disease | 18 Participants | 32 Participants | 50 Participants |
| Sex: Female, Male Female | 61 Participants | 42 Participants | 103 Participants |
| Sex: Female, Male Male | 222 Participants | 379 Participants | 601 Participants |
| Smoking status Current | 90 Participants | 103 Participants | 193 Participants |
| Smoking status Former | 91 Participants | 134 Participants | 225 Participants |
| Smoking status Never | 102 Participants | 184 Participants | 286 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 39 / 704 |
| other Total, other adverse events | 13 / 704 |
| serious Total, serious adverse events | 2 / 704 |
Outcome results
Primary
Cardiac Death, Non-fatal Recurrent Myocardial Infarction or Unscheduled Coronary Revascularisation
To determine whether coronary 18F-fluoride uptake is associated with major adverse cardiac events in patients with multi-vessel coronary artery disease and recent myocardial infarction. Participants were followed up by site investigators until the last recruited patient had completed their 2-year follow-up visit.
Time frame: 2 years
Population: Clinical follow-up was available for all study participants. At study completion, follow-up was available for 693 participants (98.4%). Over a median of 4 years (IQR, 3-5 years), there were 2582 patient-years of follow-up.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Low Coronary Atherosclerotic Plaque Activity | Cardiac Death, Non-fatal Recurrent Myocardial Infarction or Unscheduled Coronary Revascularisation | 51 Participants |
| High Coronary Atherosclerotic Plaque Activity | Cardiac Death, Non-fatal Recurrent Myocardial Infarction or Unscheduled Coronary Revascularisation | 90 Participants |
p-value: 0.295% CI: [0.89, 1.76]Log Rank
Secondary
All Cause Death
All cause death. Participants were followed up by site investigators until the last recruited patient had completed their 2-year follow-up visit.
Time frame: 2 years
Population: All cause death
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Low Coronary Atherosclerotic Plaque Activity | All Cause Death | 9 Participants |
| High Coronary Atherosclerotic Plaque Activity | All Cause Death | 30 Participants |
p-value: 0.0295% CI: [1.15, 5.12]Log Rank
Secondary
Each Individual Component End-point of the Composite End-point of Major Adverse Cardiac Event
Cardiac death, Nonfatal myocardial infarction, Unscheduled coronary revascularization
Time frame: 2 years
Population: Cardiac death, Nonfatal myocardial infarction, Unscheduled coronary revascularization
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Low Coronary Atherosclerotic Plaque Activity | Each Individual Component End-point of the Composite End-point of Major Adverse Cardiac Event | Cardiac death | 2 Participants |
| Low Coronary Atherosclerotic Plaque Activity | Each Individual Component End-point of the Composite End-point of Major Adverse Cardiac Event | Unscheduled coronary revascularization | 36 Participants |
| Low Coronary Atherosclerotic Plaque Activity | Each Individual Component End-point of the Composite End-point of Major Adverse Cardiac Event | Nonfatal myocardial infarction | 17 Participants |
| High Coronary Atherosclerotic Plaque Activity | Each Individual Component End-point of the Composite End-point of Major Adverse Cardiac Event | Nonfatal myocardial infarction | 37 Participants |
| High Coronary Atherosclerotic Plaque Activity | Each Individual Component End-point of the Composite End-point of Major Adverse Cardiac Event | Unscheduled coronary revascularization | 51 Participants |
| High Coronary Atherosclerotic Plaque Activity | Each Individual Component End-point of the Composite End-point of Major Adverse Cardiac Event | Cardiac death | 10 Participants |