Ticagrelor De-escalation Strategy in East Asian Patients With AMI

Study Overview
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Brief Summary
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Ticagrelor as nonthienopyridine, direct-acting P2Y12 receptor antagonist, had significantly greater platelet inhibition, which could reduce ischemic events at acute phase, however, resulting in more incidence of bleedings than pro-drug P2Y12 receptor inhibitor during chronic phase for management of acute myocardial infarction (AMI) following percutaneous coronary intervention (PCI). Also, East Asians have higher response to potent agent, like ticagrelor, when compared with Caucasians. With this in mind, East Asian patients will be required optimal, potentially reduced dose of ticagrelor to improve the safety profile, maintaining better vascular outcomes. Similarly, there are insufficient East Asian data on the efficacy and safety of low-dose ticagrelor in real-word practice. Whether the de-escalation strategy (ticagrelor 60/45 mg twice daily) are more adequate for clinical practice in East Asian is unclear. Therefore, the investigators design the EASTYLE study, hypothesis that low-dose ticagrelor would be more likely adequate for optimal antiplatelet treatment without increasing ischemic and bleeding events in East Asian with AMI compared with standard-dose ticagrelor. In the EASTYLE trial, further clinical data of de-escalation strategy guided AMI management in East Asian will be provided.

Detailed Description
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In EASTYLE trial, the investigators aim to evaluate the efficacy and safety of de-escalation strategy ticagrelor (60/45 mg twice daily), as compared with standard strategy ticagrelor (90 mg twice daily) in East Asian patients with AMI undergoing PCI. All eligible AMI patients receive loading dose of ticagrelor 180 mg plus aspirin 300 mg, following ticagrelor 90 mg twice daily plus aspirin 100 mg daily during the index hospitalization. Subsequently, to be randomly assigned into ticagrelor 90 mg and ticagrelor 60/45 mg twice daily in combination with aspirin 100 mg daily at discharge for at least 12-month period treatment. The investigators focusing on the efficacy and safety endpoint, is net adverse clinical and cerebrovascular events (NACCE), composite of all-cause mortality, myocardial infarction, stroke, and major bleeding.

Official Title
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A Prospective, Randomized, Open-Label, Multicenter Study Assessing Efficacy and Safety of Ticagrelor De-escalation Strategy in East Asian Acute Myocardial Infarction With Coronary Intervention: EASTYLE Trial

Conditions
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Acute Myocardial Infarction

Intervention / Treatment
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* Drug: Ticagrelor 90mg
* Drug: Ticagrelor 60/45mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients present with acute myocardial infarction undergoing PCI. Patients receive potent DAPT (Ticagrelor 180 mg loading dose followed by 90 mg twice daily plus Aspirin 300 mg loading dose followed by 100 mg daily). Patients provide written informed consent prior to enrollment. Exclusion Criteria: History of transient ischemic attack or stroke. History of upper gastrointestinal bleeding in recent 6 months. Renal dysfunction defined as serum creatinine > 2.5 mg/dl. Severe hepatic dysfunction defined as serum transaminase > 3 times normal limit. On treatment with oral anticoagulant (Vitamin K antagonists, dabigatran, rivaroxaban). Bleeding tendency. Thrombocytopenia defined by platelet < 100,000/ml. Anemia defined by hemoglobin < 10 g/dl. Current treatment with drugs interfering with CYP3A4 metabolism (to avoid interaction with Ticagrelor): Ketoconazole, itraconazole, voriconazole, clarithromycin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, atazanavir, and telithromycin. Known severe chronic obstructive pulmonary disease or bradycardia (sick sinus syndrome (SSS) or high degree AV block without pacemaker protection). Contraindication for study drugs.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Ticagrelor 90mg<br>Standard strategy group receive ticagrelor 90mg twice daily | Drug: Ticagrelor 90mg<br>* Standard strategy initially receive ticagrelor 90mg twice daily for 12 months.<br>* Other names: Brilinta 90mg;|
| Experimental: Ticagrelor 60/45mg<br>De-escalation strategy group receive ticagrelor 60 mg twice daily or 45mg twice daily if patients with body weight <60kg, or age >75 years old. | Drug: Ticagrelor 60/45mg<br>* In-hospital treatment with standard strategy ticagrelor 90mg twice daily, following de-escalation strategy ticagrelor 60/45mg twice daily after discharge for 12 months.<br>* Other names: Brilinta 60/45mg;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Net adverse clinical and cerebral events (NACCE) | Composite of all-cause death, myocardial infarction, stroke or major bleeding according to PLATO criteria. | 12 months | 
| Primary safety endpoint | Clinically significant bleeding: a composite of major or minor bleeding according to PLATO criteria. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| major adverse cardiac and cerebrovascular events (MACCE) | Defined as a composite of cardiac death, myocardial infarction, or stroke | 12 months | 
| Individual components of MACCE | Indicated cardiac death, myocardial infarction, or stroke | 12 months | 
| Secondary adverse events | Indicated non-cardiac death, target lesion/vessel revascularization, stent thrombosis. | 12 months | 
| Major or minor (PLATO) bleeding event | By PLAtelet inhibition and patient Outcomes (PLATO) criteria | 12 months | 
| Major or minor (TIMI) bleeding event | By the Thrombolysis in Myocardial Infarction (TIMI) bleeding criteria | 12 months | 
| BARC bleeding from type 1 to 5 | By Bleeding Academic Research Consortium (BARC) definition. | 12 months | 
| Premature discontinuation of study drugs | The patients cannot tolerate to be continued study drugs, due to bleeding event, or side effect. | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ticagrelor, De-escalation strategy, East Asian