Duration of Dual Anti-Platelet Therapy in Acute Coronary Syndrome
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All trials for Acute Coronary Syndrome All trials for Coronary Artery Disease All trials of 3 months dual anti-platelet therapy All trials of 12 months dual anti-platelet therapy
-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.
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+Arms and interventions
| Arm | Type | Interventions | Description |
|---|
| 3 months dual anti-platelet therapy | Active comparator | Other: 3 months dual anti-platelet therapy | 3 months dual anti-platelet therapy. |
| 12 months dual anti-platelet therapy | Active comparator | Other: 12 months dual anti-platelet therapy | 12 months dual anti-platelet therapy. |
- 3 months dual anti-platelet therapy (Other): Patients with acute coronary syndrome will be randomised to 3 months dual anti-platelet therapy.
- 12 months dual anti-platelet therapy (Other): Patients with acute coronary syndrome will be randomised to 12 months dual anti-platelet therapy.
+Outcome measures
Primary outcomes
- 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 outcomes
- 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: Gastrointestinal Bleeding [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
- Incidence: Intracranial Haemorrhage [Date of MI to 15 months]: Occurrence of event
- Time-to-event: Coronary Revascularisation [Date of MI to 15 months]: Restricted Mean Survival Time
- 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
Other outcomes
- Time-to-event: Iron Therapy [Date of MI to 15 months]: Restricted Mean Survival Time
- Incidence: Iron Therapy [Date of MI to 15 months]: Occurrence of event
- Time-to-event: Blood Transfusion [Date of MI to 15 months]: Restricted Mean Survival Time
- Incidence: Blood Transfusion [Date of MI to 15 months]: Occurrence of event
+Eligibility
Sex: All, ages: 18 Years to any
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
+Posted results
Participant flow
| Milestone | 3 Months Dual Anti-platelet Therapy | 12 Months Dual Anti-platelet Therapy |
|---|
| Started | 2526 | 2526 |
| Completed | 2526 | 2526 |
| Not completed | 0 | 0 |
Outcome results
- Time-to-event: All-cause Mortality (Primary), Mean, days: 3 Months Dual Anti-platelet Therapy 447.337 +/- 1.0542; 12 Months Dual Anti-platelet Therapy 445.196 +/- 1.1741
- Incidence: All-cause Mortality (Primary), Count of participants, Participants: 3 Months Dual Anti-platelet Therapy 68; 12 Months Dual Anti-platelet Therapy 87 (p 0.1232)
- Time-to-event: Non-cardiovascular Death (Including Fatal Bleeding) and Major Non-fatal Bleeding (Secondary), Mean, days: 3 Months Dual Anti-platelet Therapy 442.881 +/- 1.2908; 12 Months Dual Anti-platelet Therapy 440.736 +/- 1.3565
- Incidence: Non-cardiovascular Death (Including Fatal Bleeding) and Major Non-fatal Bleeding (Secondary), Number, participants: 3 Months Dual Anti-platelet Therapy 104; 12 Months Dual Anti-platelet Therapy 127 (p 0.1220)
- Time-to-event: Non-cardiovascular Death (Including Fatal Bleeding) (Secondary), Mean, days: 3 Months Dual Anti-platelet Therapy 452.453 +/- 0.5873; 12 Months Dual Anti-platelet Therapy 452.593 +/- 0.5285
- Incidence: Non-cardiovascular Death (Including Fatal Bleeding) (Secondary), Number, participants: 3 Months Dual Anti-platelet Therapy 27; 12 Months Dual Anti-platelet Therapy 29 (p 0.7789)
- Time-to-event: Major Fatal and Non-fatal Bleeding (Secondary), Mean, days: 3 Months Dual Anti-platelet Therapy 445.227 +/- 1.1719; 12 Months Dual Anti-platelet Therapy 442.790 +/- 1.2794
- Incidence: Major Fatal and Non-fatal Bleeding (Secondary), Number, participants: 3 Months Dual Anti-platelet Therapy 80; 12 Months Dual Anti-platelet Therapy 102 (p 0.0977)
- Time-to-event: Gastrointestinal Bleeding (Secondary), Mean, days: 3 Months Dual Anti-platelet Therapy 449.967 +/- 0.8887; 12 Months Dual Anti-platelet Therapy 450.562 +/- 0.7774
- Incidence: Gastrointestinal Bleeding (Secondary), Count of participants, Participants: 3 Months Dual Anti-platelet Therapy 36; 12 Months Dual Anti-platelet Therapy 38 (p 0.8208)
- Time-to-event: Cardiovascular Death and Non-fatal Myocardial Infarction (Secondary), Mean, days: 3 Months Dual Anti-platelet Therapy 422.876 +/- 2.1559; 12 Months Dual Anti-platelet Therapy 424.670 +/- 2.1010
- Incidence: Cardiovascular Death and Non-fatal Myocardial Infarction (Secondary), Count of participants, Participants: 3 Months Dual Anti-platelet Therapy 236; 12 Months Dual Anti-platelet Therapy 226 (p 0.6158)
- Time-to-event: Cardiovascular Mortality (Cardiac and Non-cardiac) (Secondary), Mean, days: 3 Months Dual Anti-platelet Therapy 449.943 +/- 0.8891; 12 Months Dual Anti-platelet Therapy 447.897 +/- 1.0372
- Incidence: Cardiovascular Mortality (Cardiac and Non-cardiac) (Secondary), Count of participants, Participants: 3 Months Dual Anti-platelet Therapy 40; 12 Months Dual Anti-platelet Therapy 56 (p 0.1020)
- Time-to-event: Myocardial Infarction (Fatal and Non-fatal) (Secondary), Mean, days: 3 Months Dual Anti-platelet Therapy 424.471 +/- 2.1157; 12 Months Dual Anti-platelet Therapy 427.444 +/- 2.0181
- Incidence: Myocardial Infarction (Fatal and Non-fatal) (Secondary), Count of participants, Participants: 3 Months Dual Anti-platelet Therapy 221; 12 Months Dual Anti-platelet Therapy 203 (p 0.3623)
- Incidence: Intracranial Haemorrhage (Secondary), Count of participants, Participants: 3 Months Dual Anti-platelet Therapy 0; 12 Months Dual Anti-platelet Therapy 10
- Time-to-event: Coronary Revascularisation (Secondary), Mean, days: 3 Months Dual Anti-platelet Therapy 414.488 +/- 2.3733; 12 Months Dual Anti-platelet Therapy 417.081 +/- 2.3383
- Incidence: Coronary Revascularisation (Secondary), Count of participants, Participants: 3 Months Dual Anti-platelet Therapy 286; 12 Months Dual Anti-platelet Therapy 259 (p 0.2324)
- Time-to-event: Stent Thrombosis (Secondary), Mean, days: 3 Months Dual Anti-platelet Therapy 450.566 +/- 0.8329; 12 Months Dual Anti-platelet Therapy 450.026 +/- 0.9228
- 7 more outcome measures not shown.
Adverse events
Time frame: 15 months from date of randomisation.
| Arm | Deaths | Serious adverse events | Other adverse events |
|---|
| 3 Months Dual Anti-platelet Therapy | 68/2526 (2.7%) | 0/2526 (0.0%) | 0/2526 (0.0%) |
| 12 Months Dual Anti-platelet Therapy | 87/2526 (3.4%) | 0/2526 (0.0%) | 0/2526 (0.0%) |
Limitations and caveats: The major limitation is that early trial termination meant the target sample size was not achieved, leaving an underpowered trial which was unable to address its primary endpoint. The recruitment suspension due to COVID-19, and the subsequent delays in re-opening of the study sites and lack of staff capacity significantly affected recruitment.
+Locations (1)
| Facility | City | Country | Status |
|---|
| Edinburgh Royal Infirmary | Edinburgh | United Kingdom | |
+Study documents
+Investigators
- David Newby, Principal investigator, University of Edinburgh