Myocardial Infarction, Unstable Angina
Conditions
Keywords
timing, intervention, early, delayed, acute coronary syndromes, PCI, angiography, Non ST-segment elevation myocardial infarction, unstable angina
Brief summary
The timing of intervention study is a prospective, randomized, international, multicentre comparison of the relative efficacy, safety, and cost effectiveness of a management strategy of coronary angiography and intervention performed within 24 hours of randomization versus delayed coronary angiography and intervention in patients after 36 hours with acute coronary syndromes (ACS).
Interventions
PROCEDUREEarly Coronary Intervention
Perform coronary angiography and intervention (either percutaneous coronary intervention \[PCI\] or coronary artery bypass graft \[CABG\] surgery) as soon as possible (and within 24 hours of randomisation).
PROCEDUREDelayed Coronary Intervention
Perform coronary angiography and intervention (either percutaneous coronary intervention \[PCI\] or coronary artery bypass graft \[CABG\] surgery) any time after 36 hours after randomisation.
Sponsors
Canadian Institutes of Health Research (CIHR)
Hamilton Health Sciences Corporation
Population Health Research Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients presenting or admitted to hospital with symptoms suspected to represent an acute coronary syndrome (unstable angina or MI without persistent ST elevation) i.e., clinical history consistent with new onset, or a worsening pattern, of characteristic ischemic chest pain or ischemic symptoms occurring at rest or with minimal activity (lasting longer than five minutes or requiring sublingual nitroglycerin for relief of the pain) 2. Able to randomise within 24 hours of the onset of the most recent episode of symptoms 3. At least two of the three following additional criteria: * Age more than or equal to 60 years * Troponin T or I or Creatine Kinase - Myocardial Bands (CK-MB) above the upper limit of normal for the local institution * ElectroCardioGram (ECG) changes compatible with ischemia (i.e., ST depression at least 1 mm in two contiguous leads or T wave inversion mroe than 3 mm or any dynamic ST shift or transient ST elevation) 4. Written informed consent dated and signed
Exclusion criteria
1. Age less than 21 years 2. Not a suitable candidate for revascularisation 3. Co-morbid condition with life expectancy less than six months
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Composite of Death, Myocardial (re-) Infarction, or Stroke | 180 days |
Secondary
| Measure | Time frame |
|---|---|
| First Occurrence of Any Component of the Composite of Death, MI, or Refractory Ischemia | 180 days |
| Composite of Death, MI, Stroke, Refractory Ischemia or Repeat Revascularization at 180 Days | 180 days |
| Stroke at 30 Days and 180 Days | 180 days |
| Need for Mechanical or Pharmacological Coronary Revascularization (i.e. Thrombolysis, PCI, CABG) at Days 30, 90, and 180 | 180 days |
| In-hospital Major Bleeding | Hospital discharge |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Early Coronary angiography and intervention (either percutaneous coronary intervention \[PCI\] or coronary artery bypass graft \[CABG\] surgery) as soon as possible (within 24 hours of randomisation). | 1,593 |
| Delayed Delayed intervention: Coronary angiography and intervention (either percutaneous coronary intervention \[PCI\] or coronary artery bypass graft \[CABG\] surgery) any time after 36 hours after randomisation. | 1,438 |
| Total | 3,031 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 5 | 1 |
Baseline characteristics
| Characteristic | Early | Delayed | Total |
|---|---|---|---|
| Age, Customized Age | 65.1 years STANDARD_DEVIATION 0 | 65.8 years STANDARD_DEVIATION 0 | 65.5 years STANDARD_DEVIATION 0 |
| Sex: Female, Male Female | 554 Participants | 498 Participants | 1052 Participants |
| Sex: Female, Male Male | 1039 Participants | 940 Participants | 1979 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
Primary
Composite of Death, Myocardial (re-) Infarction, or Stroke
Time frame: 180 days
Population: All patients were included in the final intention-to-treat analysis. Event rates in the two groups were estimated with the use of the Kaplan-Meier method. The hazard ratio and two-sided 95% confidence intervals were calculated with the use of a Cox proportional-hazards model.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Early Intervention | Composite of Death, Myocardial (re-) Infarction, or Stroke | 153 participants |
| Delayed Intervention | Composite of Death, Myocardial (re-) Infarction, or Stroke | 163 participants |
p-value: 0.1595% CI: [0.68, 1.06]Regression, Logistic
Secondary
Composite of Death, MI, Stroke, Refractory Ischemia or Repeat Revascularization at 180 Days
Time frame: 180 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Early Intervention | Composite of Death, MI, Stroke, Refractory Ischemia or Repeat Revascularization at 180 Days | 264 Eparticipants |
| Delayed Intervention | Composite of Death, MI, Stroke, Refractory Ischemia or Repeat Revascularization at 180 Days | 280 Eparticipants |
p-value: 0.0495% CI: [0.71, 0.99]Regression, Logistic
Secondary
First Occurrence of Any Component of the Composite of Death, MI, or Refractory Ischemia
Time frame: 180 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Early Intervention | First Occurrence of Any Component of the Composite of Death, MI, or Refractory Ischemia | 151 participants |
| Delayed Intervention | First Occurrence of Any Component of the Composite of Death, MI, or Refractory Ischemia | 186 participants |
p-value: 0.00395% CI: [0.58, 0.89]Regression, Logistic
Secondary
In-hospital Major Bleeding
Time frame: Hospital discharge
Secondary
Need for Mechanical or Pharmacological Coronary Revascularization (i.e. Thrombolysis, PCI, CABG) at Days 30, 90, and 180
Time frame: 180 days
Secondary
Stroke at 30 Days and 180 Days
Time frame: 180 days