Ticagrelor De-escalation Strategy in AMI Patients

EASTYLE (DE-escAlation Strategy for Optimal Ticagrelor Therapy in Acute MYocardiaL Infarction PatiEnts, Prospective, Multicenter, Randomized) Trial

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.

Study Overview

• Status: Recruiting
• Conditions: Acute Myocardial Infarction
• Intervention / Treatment: Drug: De-escalation strategy; Drug: Conventional 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.

• Study Type: Interventional
• Enrollment (Estimated): 2312
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Moo Hyun Kim, MD, PhD; Phone Number: +82-51-240-2976; Email: kimmh@dau.ac.kr
• Study Contact Backup: Name: Young-Hoon Jeong, MD, PhD; Phone Number: +82-2-2610-6795; Email: goodoctor@naver.com

Study Locations

• South Korea
  • Busan, South Korea, 602-715
    • Recruiting
    • DongA University Hospital
    • Contact: Moo Hyun Kim, M.D.; Phone Number: +82-51-240-2976; Email: kimmh@dau.ac.kr
    • Principal Investigator: Moo Hyun Kim, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: De-escalation strategy; 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	Drug: De-escalation strategy; 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).; Other Names: Ticagrelor 60 mg, aspirin early discontinuation
Active Comparator: Conventional strategy; PCI ~ 12 months: ticagrelor 90 mg twice daily + aspirin 100 mg once daily	Drug: Conventional strategy; Conventional stratetgy indicates conventional DAPT including ticagrelor 90 mg twice daily and aspirin 100 mg once daily during 12 months.; Other Names: Ticagrelor 90 mg, DAPT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary endpoint (NACE)	MACCE (all-cause death, non-fatal myocardial infarction, stent thrombosis or non-fatal stroke) + major bleeding (BARC type 2, 3, or 5 bleeding)	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
TLR	target lesion revascularization	12 months
TVR	target vessel revascularization	12 months
Major adverse cardiac and cerebrovascular events (MACCE)	all-cause death, non-fatal myocardial infarction, stent thrombosis or non-fatal stroke	12 months
Bleeding events	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	12 months
All-cause death	any mortality	12 months
CV death	Death related CV system	12 months
MI	Myocardial infarction	12 months
Stent thrombosis	definite or probable stent thrombosis by Academic Research Consortium (ARC) definition	12 months
Ischemic stroke	Stroke	12 months
Cardiac death, or MI	Coronary thrombotic events	12 months
Cardiac death, MI or stent thrombosis	Coronary thrombotic events	12 months
Cardiovascular death, MI or stroke	MACE	12 months
Any revascularization	Re-PCI during follow-up	12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Type of AMI	STEMI vs. NSTEMI	12 months
HBR	presence of HBR (high bleeding risk) criteria	12 months
DM	presence of diabetes mellitus	12 months
CKD	presence of chronic kidney disease	12 months
Anemia	presence of anemia	12 months
Gender	Male vs. female	12 months
Age	Old vs. young age (65 yo, 75 yo)	12 months
Complex PCI	Presence of complex PCI	12 months
GDMT	Presence of guideline-directed medical therapy	12 months
Type of statin	Rosuvastatin vs. other statins	12 months
CHF	Presence of congestive heart failure	12 months
PAD	Presence of peripheral artery disease	12 months
PFT	VerifyNow assy	12 months
Predictors of MACCE	Clinical impact of de-esclation strategy on MACCE	12 months
Predictors of maor bleeding	Clinical impact of de-esclation strategy on major bleeding	12 months

Collaborators and Investigators

• Sponsor: Dong-A University
• Collaborators: Biotronik SE & Co. KG; Samjin Pharmaceutical Co., Ltd.
• Investigators: Principal Investigator: Moo Hyun Kim, MD, PhD, Dong-A University Hospital, Busan, Republic of Korea

Publications and helpful links

General Publications

• 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.
• Gorog DA, Ferreiro JL, Ahrens I, Ako J, Geisler T, Halvorsen S, Huber K, Jeong YH, Navarese EP, Rubboli A, Sibbing D, Siller-Matula JM, Storey RF, Tan JWC, Ten Berg JM, Valgimigli M, Vandenbriele C, Lip GYH. De-escalation or abbreviation of dual antiplatelet therapy in acute coronary syndromes and percutaneous coronary intervention: a Consensus Statement from an international expert panel on coronary thrombosis. Nat Rev Cardiol. 2023 Dec;20(12):830-844. doi: 10.1038/s41569-023-00901-2. Epub 2023 Jul 20.
• Gorog DA, Jeyalan V, Markides RIL, Navarese EP, Jeong YH, Farag M. Comparison of De-escalation of DAPT Intensity or Duration in East Asian and Western Patients with ACS Undergoing PCI: A Systematic Review and Meta-analysis. Thromb Haemost. 2023 Aug;123(8):773-792. doi: 10.1055/s-0043-57030. Epub 2023 Apr 18.
• Kang MG, Ahn JH, Kim K, Koh JS, Park JR, Hwang SJ, Park Y, Tantry US, Gurbel PA, Hwang JY, Jeong YH. Prevalence of adverse events during ticagrelor versus clopidogrel treatment and its association with premature discontinuation of dual antiplatelet therapy in East Asian patients with acute coronary syndrome. Front Cardiovasc Med. 2022 Dec 12;9:1053867. doi: 10.3389/fcvm.2022.1053867. eCollection 2022.
• Kubica J, Adamski P, Gorog DA, Kubica A, Jilma B, Budaj A, Siller-Matula JM, Gurbel PA, Alexopoulos D, Badariene J, Dabrowski P, Dudek D, Giannitsis E, Horszczaruk G, Jaguszewski MJ, James S, Jeong YH, Kryjak M, Niezgoda P, Ostrowska M, Patti G, Romanek J, Di Somma S, Specchia G, Tantry U, Gasior M, Tycinska A, Wojakowski W, Buszko K, Gil R, Gruchala M, Kasprzak J, Kleinrok A, Legutko J, Lesiak M, Navarese EP. Low-dose ticagrelor with or without acetylsalicylic acid in patients with acute coronary syndrome: Rationale and design of the ELECTRA-SIRIO 2 trial. Cardiol J. 2022;29(1):148-153. doi: 10.5603/CJ.a2021.0118. Epub 2021 Oct 8. No abstract available.
• Kim L, Choe JC, Ahn JH, Lee HW, Oh JH, Choi JH, Lee HC, Cha KS, Hong TJ, Jeong YH, Park JS. Temporal Trends of Bleeding Episodes during Half- vs. Standard-Dose Ticagrelor in Acute Coronary Syndrome Patients with Low Platelet Reactivity: A Randomized BLEEDING-ACS Trial. J Clin Med. 2021 Mar 10;10(6):1159. doi: 10.3390/jcm10061159.
• Kim HK, Tantry US, Smith SC Jr, Jeong MH, Park SJ, Kim MH, Lim DS, Shin ES, Park DW, Huo Y, Chen SL, Bo Z, Goto S, Kimura T, Yasuda S, Chen WJ, Chan M, Aradi D, Geisler T, Gorog DA, Sibbing D, Lip GYH, Angiolillo DJ, Gurbel PA, Jeong YH. The East Asian Paradox: An Updated Position Statement on the Challenges to the Current Antithrombotic Strategy in Patients with Cardiovascular Disease. Thromb Haemost. 2021 Apr;121(4):422-432. doi: 10.1055/s-0040-1718729. Epub 2020 Nov 10.
• Park Y, Koh JS, Lee JH, Park JH, Shin ES, Oh JH, Chun W, Lee SY, Bae JW, Kim JS, Kim W, Suh JW, Yang DH, Hong YJ, Chan MY, Kang MG, Park HW, Hwang SJ, Hwang JY, Ahn JH, Choi SW, Jeong YH; HEALING-AMI Investigators. Effect of Ticagrelor on Left Ventricular Remodeling in Patients With ST-Segment Elevation Myocardial Infarction (HEALING-AMI). JACC Cardiovasc Interv. 2020 Oct 12;13(19):2220-2234. doi: 10.1016/j.jcin.2020.08.007.

Study record dates

Study Major Dates

• Study Start (Actual): March 27, 2023
• Primary Completion (Estimated): January 15, 2027
• Study Completion (Estimated): January 31, 2028

Study Registration Dates

• First Submitted: February 11, 2021
• First Submitted That Met QC Criteria: February 11, 2021
• First Posted (Actual): February 16, 2021

Study Record Updates

• Last Update Posted (Estimated): October 1, 2025
• Last Update Submitted That Met QC Criteria: September 26, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Ticagrelor; DAPT; De-escalation strategy; Abbreviated strategy
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Myocardial Infarction; Infarction; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Nucleic Acids, Nucleotides, and Nucleosides; Purines; Nucleosides; Ribonucleosides; Adenosine; Purine Nucleosides; Ticagrelor; 2'-deoxythymidylyl-(3'-5')-2'-deoxyadenosine
• Other Study ID Numbers: EASTYLE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No