Ticagrelor De-escalation Strategy in East Asian Patients With AMI

Overview

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.

Full Title of Study: “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”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: December 31, 2023

Detailed Description

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.

Interventions

  • Drug: Ticagrelor 90mg
    • Standard strategy initially receive ticagrelor 90mg twice daily for 12 months.
  • Drug: Ticagrelor 60/45mg
    • In-hospital treatment with standard strategy ticagrelor 90mg twice daily, following de-escalation strategy ticagrelor 60/45mg twice daily after discharge for 12 months.

Arms, Groups and Cohorts

  • Other: Ticagrelor 90mg
    • Standard strategy group receive ticagrelor 90mg twice daily
  • Experimental: Ticagrelor 60/45mg
    • 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.

Clinical Trial Outcome Measures

Primary Measures

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

Secondary Measures

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

Participating in This Clinical Trial

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.

Gender Eligibility: All

Minimum Age: 20 Years

Maximum Age: 80 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Dong-A University
  • Provider of Information About this Clinical Study
    • Principal Investigator: Moo Hyun Kim, Professor, Dept. of Cardiology Dong-A University Hospital – Dong-A University
  • Overall Official(s)
    • Moo Hyun Kim, M.D., Principal Investigator, Dong-A University Hospital, Busan, Republic of Korea
  • Overall Contact(s)
    • Moo Hyun Kim, M.D., +82-51-240-2976, kimmh@dau.ac.kr

References

Goto S, Huang CH, Park SJ, Emanuelsson H, Kimura T. Ticagrelor vs. clopidogrel in Japanese, Korean and Taiwanese patients with acute coronary syndrome — randomized, double-blind, phase III PHILO study. Circ J. 2015;79(11):2452-60. doi: 10.1253/circj.CJ-15-0112. Epub 2015 Sep 16.

Jin C, Kim MH, Bang J, Serebruany V. A Prospective, Randomized, Open-Label, Blinded, Endpoint Study Exploring Platelet Response to Half-Dose Prasugrel and Ticagrelor in Patients with the Acute Coronary Syndrome: HOPE-TAILOR Study. Cardiology. 2017;138(4):201-206. doi: 10.1159/000478000. Epub 2017 Aug 16.

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