Ticagrelor De-escalation Strategy in AMI Patients

Dong-A University

Status and phase: Enrolling; Phase 4

Conditions: Acute Myocardial Infarction

Treatments: Drug: Conventional strategy; Drug: De-escalation strategy

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT04755387

EASTYLE

Details and patient eligibility

About

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.

Full 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.

Enrollment: 2,312 estimated patients

Sex: All

Ages: 19 to 80 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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2,312 participants in 2 patient groups

De-escalation strategy

Experimental group

Description:

PCI \~ 1 month: ticagrelor 90 mg twice daily + aspirin 100 mg once daily 1 \~ 3 months: ticagrelor 60 mg twice daily + aspirin 100 mg once daily 3 \~ 12 months: ticagrelor 60 mg twice daily

Treatment:

Drug: De-escalation strategy

Conventional strategy

Active Comparator group

Description:

PCI \~ 12 months: ticagrelor 90 mg twice daily + aspirin 100 mg once daily

Treatment:

Drug: Conventional strategy