Acute Myocardial Infarction
Conditions
Keywords
Ticagrelor, DAPT, De-escalation strategy, Abbreviated strategy
Brief summary
DAPT de-escalation strategies to reduce bleeding include de-escalation of DAPT intensity (downgrading from potent P2Y12 inhibitor at conventional doses to either clopidogrel or reduced-dose prasugrel) or abbreviation of DAPT duration. The EASTYLE trial will evaluate a hybrid DAPT de-escalation strategy (reduced-dose ticagrelor, followed by aspirin early discontinuation) in AMI patients, compared with a conventional DAPT strategy.
Detailed description
In ACS patients undergoing percutaneous coronary intervention, conventional dual antiplatelet therapy (DAPT) for patients with acute coronary syndromes undergoing percutaneous coronary intervention comprises aspirin with a potent P2Y12 inhibitor (prasugrel or ticagrelor) for 12 months. Although this approach reduces ischaemic risk, patients are exposed to a substantial risk of bleeding during the stabilized period. Strategies to reduce bleeding include de-escalation of DAPT intensity (downgrading from potent P2Y12 inhibitor at conventional doses to either clopidogrel or reduced-dose prasugrel) or abbreviation of DAPT duration. Abbreviation of DAPT duration after 1-6 months, followed by monotherapy with aspirin or a P2Y12 inhibitor, reduces bleeding without an increase in ischaemic events in patients at high bleeding risk, particularly those without high ischaemic risk. Either strategy requires assessment of the ischaemic and bleeding risks of each individual. Previous clinical and laboratory evidence demonstrates that a conventional-dose of ticagrelor has a potent antiplatelet effect, which appears to have a potential to increase the risk of bleeding during the stabilized period. Adjunctive use of aspirin to P2Y12 inhibitor would be important to protect the risk of thrombotic events in AMI patients, which use has a limited benefit with increased bleeding rate during the the stabilized period. The EASTYLE trial will evaluate clinical benefit of step-down de-escalation DAPT strategy including downgrading of P2Y12 inhibition (from 90 mg to 60 mg ticagrelor at 1 month post-PCI) and abbreviation of DAPT duration (aspirin discontinuation at 3 months post-PCI), compared with a conventional DAPT strategy in AMI patients. This trial will support that the optimal platelet inhibition would be attenuated over time even in AMI patients. The result will make a big step toward precision medicine in the field of antiplatelet treatment in AMI patients.
Interventions
De-escalation strategy indicates conventional DAPT (ticagrelor 90 mg twice daily + aspirin 100 mg once daily) for 1 month, followed by de-escalation DAPT (ticagrelor 60 mg twice daily + aspirin 100 mg once daily) between 1 and 3 months. Between 3 and 12 months, patients will be treated with ticagrelor monotherapy (ticagrelor 60 mg twice daily).
Conventional stratetgy indicates conventional DAPT including ticagrelor 90 mg twice daily and aspirin 100 mg once daily during 12 months.
Sponsors
Biotronik SE & Co. KG
Samjin Pharmaceutical Co., Ltd.
Dong-A University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis with acute myocardial infarction. * Age ≥19 year-old * Successful PCI with ultrathin bioresorbable polymer sirolimus-eluting stents (Orsiro; Biotronik AG). * Provision of informed consent.
Exclusion criteria
* Any prior event of hemorrhagic stroke or ICH. * Active bleeding (e.g., GI bleeding, ICH) or high-risk of serious bleeding. * Bleeding diathesis or coagulopathy (e.g., hemoglobin ≤ 10 g/dL or platelet count \< 100,000/μL, bleeding needing transfusion within 30 days, and so on). * Allergy to stent metal, contrat media, and antiplatelet regimens. * Moderate to severe hepatic dysfunction (Child-Pugh class B or C). * Need for oral anticoagulation therapy. * Current or potential pregnancy. * Currently treated with strong CYP3A4 inhibitors. * Life expectancy \<1 year.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary endpoint (NACE) | 12 months | MACCE (all-cause death, non-fatal myocardial infarction, stent thrombosis or non-fatal stroke) + major bleeding (BARC type 2, 3, or 5 bleeding) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Bleeding events | 12 months | BARC type 2, 3 or 5 bleeding; BARC 3 or 5 bleeding; TIMI major or minor bleeding; GUSTO severe or moderate bleeding; ISTH major bleeding |
| All-cause death | 12 months | any mortality |
| CV death | 12 months | Death related CV system |
| MI | 12 months | Myocardial infarction |
| Stent thrombosis | 12 months | definite or probable stent thrombosis by Academic Research Consortium (ARC) definition |
| Ischemic stroke | 12 months | Stroke |
| Major adverse cardiac and cerebrovascular events (MACCE) | 12 months | all-cause death, non-fatal myocardial infarction, stent thrombosis or non-fatal stroke |
| Cardiac death, MI or stent thrombosis | 12 months | Coronary thrombotic events |
| Cardiovascular death, MI or stroke | 12 months | MACE |
| TLR | 12 months | target lesion revascularization |
| TVR | 12 months | target vessel revascularization |
| Any revascularization | 12 months | Re-PCI during follow-up |
| Cardiac death, or MI | 12 months | Coronary thrombotic events |
Other
| Measure | Time frame | Description |
|---|---|---|
| Type of AMI | 12 months | STEMI vs. NSTEMI |
| Predictors of maor bleeding | 12 months | Clinical impact of de-esclation strategy on major bleeding |
| HBR | 12 months | presence of HBR (high bleeding risk) criteria |
| DM | 12 months | presence of diabetes mellitus |
| CKD | 12 months | presence of chronic kidney disease |
| Anemia | 12 months | presence of anemia |
| Gender | 12 months | Male vs. female |
| Age | 12 months | Old vs. young age (65 yo, 75 yo) |
| Complex PCI | 12 months | Presence of complex PCI |
| GDMT | 12 months | Presence of guideline-directed medical therapy |
| Type of statin | 12 months | Rosuvastatin vs. other statins |
| CHF | 12 months | Presence of congestive heart failure |
| PAD | 12 months | Presence of peripheral artery disease |
| PFT | 12 months | VerifyNow assy |
| Predictors of MACCE | 12 months | Clinical impact of de-esclation strategy on MACCE |
Countries
South Korea
Contacts
Primary ContactMoo Hyun Kim, MD, PhD
Backup ContactYoung-Hoon Jeong, MD, PhD
Outcome results
None listed