Acute Coronary Syndrome, Coronary Artery Disease
Conditions
Brief summary
Despite substantial evidence supporting the use of dual anti-platelet therapy in patients with acute coronary syndrome, there remains major uncertainty regarding the optimal duration of therapy. Recent evidence suggests that shorter durations of dual anti-platelet therapy are superior because the avoidance of atherothrombotic events is counterbalanced by the greater risks of excess major bleeding with apparent increases in all-cause mortality with longer durations. We here propose an international randomised controlled trial of 18,318 patients with type 1 myocardial infarction allocated to differing durations of dual anti-platelet therapy. We will use electronic health record linkage to track duration of therapy and clinical outcomes in a real-world, real-time, efficient and highly cost-effective trial. This has the potential to define treatment duration, settle a major outstanding international controversy, and influence modern cardiology practice across the world.
Interventions
OTHER3 months dual anti-platelet therapy
Patients with acute coronary syndrome will be randomised to 3 months dual anti-platelet therapy.
OTHER12 months dual anti-platelet therapy
Patients with acute coronary syndrome will be randomised to 12 months dual anti-platelet therapy.
Sponsors
University of Edinburgh
British Heart Foundation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Aged ≥18 years * Clinical diagnosis of Type 1 myocardial infarction within 12 weeks * In the opinion of the attending clinician requires dual anti-platelet therapy with aspirin and a P2Y12 receptor antagonist * Resident in the country of recruitment with their unique health identifier * The attending clinician has equipoise regarding the duration of therapy * Provision of informed consent
Exclusion criteria
* Clear indication for specific duration of dual anti-platelet therapy * Type 2 myocardial infarction * Contraindication to aspirin or P2Y12 receptor antagonist * Non-resident in the country of recruitment * Previous recruitment into the trial * Inability or unwilling to give informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time-to-event: All-cause Mortality | Date of index MI to 15 months | Restricted Mean Survival Time |
| Incidence: All-cause Mortality | Date of index MI to 15 months | Occurrence of event |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence: Coronary Revascularisation | Date of MI to 15 months | Occurrence of event |
| Time-to-event: Stent Thrombosis | Date of MI to 15 months | Restricted Mean Survival Time |
| Incidence: Stent Thrombosis | Date of MI to 15 months | Occurrence of event |
| Time-to-event: Thrombotic Stroke | Date of MI to 15 months | Restricted Mean Survival Time |
| Incidence: Thrombotic Stroke | Date of MI to 15 months | Occurrence of event |
| Time-to-event: Cardiovascular Death and Non-fatal Myocardial Infarction | Date of MI to 15 months | Restricted Mean Survival Time |
| Incidence: Cardiovascular Death and Non-fatal Myocardial Infarction | Date of MI to 15 months | Occurrence of event |
| Time-to-event: Cardiovascular Mortality (Cardiac and Non-cardiac) | Date of MI to 15 months | Restricted Mean Survival Time |
| Incidence: Cardiovascular Mortality (Cardiac and Non-cardiac) | Date of MI to 15 months | Occurrence of event |
| Time-to-event: Myocardial Infarction (Fatal and Non-fatal) | Date of MI to 15 months | Restricted Mean Survival Time |
| Incidence: Myocardial Infarction (Fatal and Non-fatal) | Date of MI to 15 months | Occurrence of event |
| Time-to-event: Non-cardiovascular Death (Including Fatal Bleeding) and Major Non-fatal Bleeding | Date of MI to 15 months | Restricted Mean Survival Time |
| Incidence: Non-cardiovascular Death (Including Fatal Bleeding) and Major Non-fatal Bleeding | Date of MI to 15 months | Occurrence of event |
| Time-to-event: Non-cardiovascular Death (Including Fatal Bleeding) | Date of MI to 15 months | Restricted Mean Survival Time |
| Incidence: Non-cardiovascular Death (Including Fatal Bleeding) | Date of MI to 15 months | Occurrence of event |
| Time-to-event: Major Fatal and Non-fatal Bleeding | Date of MI to 15 months | Restricted Mean Survival Time |
| Incidence: Major Fatal and Non-fatal Bleeding | Date of MI to 15 months | Occurrence of event |
| Time-to-event: Gastrointestinal Bleeding | Date of MI to 15 months | Restricted Mean Survival Time |
| Incidence: Intracranial Haemorrhage | Date of MI to 15 months | Occurrence of event |
| Incidence: Gastrointestinal Bleeding | Date of MI to 15 months | Occurrence of event |
| Time-to-event: Coronary Revascularisation | Date of MI to 15 months | Restricted Mean Survival Time |
Countries
United Kingdom
Contacts
PRINCIPAL_INVESTIGATORDavid Newby
University of Edinburgh
Participant flow
Recruitment details
All randomised participants in database.
Pre-assignment details
42 participants were excluded from the ITT population following randomisation, those who subsequently became ineligible after a diagnosis other than Type 1 myocardial infarction (MI) and withdrawn from the trial were excluded.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 63.4 years STANDARD_DEVIATION 10.8 |
| Clinical Management at Randomisation Bare metal stent | 27 Participants |
| Clinical Management at Randomisation CABG surgery | 81 Participants |
| Clinical Management at Randomisation Conservative | 136 Participants |
| Clinical Management at Randomisation Drug eluting stent | 1366 Participants |
| Clinical Management at Randomisation ICA planned | 835 Participants |
| Clinical Management at Randomisation Medical management | 164 Participants |
| Race/Ethnicity, Customized Asian | 18 Participants |
| Race/Ethnicity, Customized Black | 1 Participants |
| Race/Ethnicity, Customized Data not collected for Scotland or New Zealand | 2164 Participants |
| Race/Ethnicity, Customized Missing | 6 Participants |
| Race/Ethnicity, Customized Mixed | 1 Participants |
| Race/Ethnicity, Customized Not stated or not known | 54 Participants |
| Race/Ethnicity, Customized Other | 2 Participants |
| Race/Ethnicity, Customized White | 284 Participants |
| Region of Enrollment New Zealand | 257 participants |
| Region of Enrollment United Kingdom | 4534 participants |
| Sex/Gender, Customized Sex; Female, Male Female | 685 Participants |
| Sex/Gender, Customized Sex; Female, Male Male | 1838 Participants |
| Sex/Gender, Customized Sex; Female, Male Not available | 4 Participants |
| Social Deprivation Missing | 30 Participants |
| Social Deprivation Not recorded | 145 Participants |
| Social Deprivation Quintile 1 (most deprived) | 393 Participants |
| Social Deprivation Quintile 2 | 484 Participants |
| Social Deprivation Quintile 3 | 505 Participants |
| Social Deprivation Quintile 4 | 489 Participants |
| Social Deprivation Quintile 5 (least deprived) | 920 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 68 / 2,526 | 87 / 2,526 |
| other Total, other adverse events | 0 / 2,526 | 0 / 2,526 |
| serious Total, serious adverse events | 0 / 2,526 | 0 / 2,526 |
Outcome results
None listed