Genotype-Guided Abbreviated DAPT Versus Un-Guided De-escalation Therapy in Patients With ACS and HBR (GUIDE-HBR)

SMart Angioplasty Research Team- Genotype-Guided Abbreviated DUal AntIplatelet Therapy Versus Un-Guided De-escalation Therapy in Patients With Acute Coronary SyndromE and High Bleeding Risk (SMART-GUIDE-HBR)

The aim of this study is to assess the safety and efficacy of the CYP2C19 genotype-guided abbreviated dual antiplatelet therapy (DAPT) strategy versus the un-guided stepwise intensity de-escalation of DAPT strategy in patients with acute coronary syndrome (ACS) and high bleeding risk (HBR) undergoing percutaneous coronary intervention (PCI).

Study Overview

• Status: Not yet recruiting
• Conditions: High Bleeding Risk; Acute Coronary Syndrome (ACS) Undergoing Percutaneous Coronary Intervention (PCI)
• Intervention / Treatment: Drug: P2Y12 antagonist monotherapy; Drug: clopidogrel + aspirin

Detailed Description

Current guidelines recommend reducing the duration of dual antiplatelet therapy (abbreviated DAPT) or de-escalating P2Y12 inhibitor intensity (de-escalation therapy) in patients at risk of major bleeding, even in patients with acute coronary syndromes. A network meta-analysis that indirectly compared these two strategies found that abbreviated dual antiplatelet therapy reduced major bleeding compared with de-escalated dual antiplatelet therapy.

Unlike prasugrel and ticagrelor, which are potent P2Y12 inhibitors, clopidogrel is activated in the liver via the cytochrome P450 2C19 (CYP2C19) metabolic pathway to exert its antiplatelet effects. Its use as monotherapy requires caution, given that CYP2C19 genotypes that may be resistant to clopidogrel are more prevalent in Asian populations than in Western populations.

Therefore, this study aimed to compare the clinical outcomes and confirm the efficacy and safety of an abbreviated dual antiplatelet therapy (Abbreviated DAPT, P2Y12 inhibitor monotherapy) strategy based on CYP2C19 genetic testing and a step-down DAPT strategy (De-escalation therapy) after 1 month of maintenance potent P2Y12 inhibitor-based dual antiplatelet therapy in patients at HBR who underwent PCI for ACS.

• Study Type: Interventional
• Enrollment (Estimated): 3000
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Joo-Yong Hahn, MD, PhD; Phone Number: 82-2-3410-3419; Email: jyhahn@skku.edu
• Study Contact Backup: Name: Ki Hong Choi, MD, PhD; Phone Number: 82-2-3410-6653; Email: cardiokh@gmail.com

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center
    • Contact: Ki Hong Choi; Phone Number: 82-2-3410-6653; Email: cardiokh@gmail.com
    • Contact: Joo-Yong Hahn, MD, PhD; Phone Number: 82-2-3410-3419; Email: jyhahn@skku.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients must be at least 19 years of age
• Patients who is able to understand risks, benefits and treatment alternatives and sign informed consent voluntarily.
• Patients presenting with ACS (ST-elevation myocardial infarction [STEMI] or non-ST-elevation [NSTE] ACS).
• Patients with at least one lesion with equal or greater than 50% diameter stenosis requiring treatment with drug-eluting stents in native coronary artery or graft.
• Patients with high bleeding risk (by ARC-HBR definition or PRECISE-DAPT score 25 or more)

Exclusion Criteria:

• Patients unable to provide consent.
• Patients who need chronic anti-coagulation therapy.
• Patients suffering from cardiogenic shock or cardiac arrest
• Patients with known intolerance to aspirin, all P2Y12 inhibitors, or components of drug-eluting stents.
• Clinically significant out of range values for platelet count (< 50,000/mm3) or hemoglobin (<8 g/dL) at screening
• Non-cardiac co-morbid conditions are present with life expectancy <1 year or that may result in protocol non-compliance (per site investigator's medical judgment).
• Pregnant or lactating women.

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
Active Comparator: Genotype-guided abbreviated DAPT; Rapid (CYP2C19*1/*17 or *17/*17) or normal metabolizers (CYP2C19*1/*1) for clopidogrel will receive clopidogrel monotherapy and intermediate or poor metabolizers will receive potent P2Y12 inhibitor (prasugrel or ticagrelor) monotherapy (patients carrying a CYP2C19*2 or *3 alleles) after 1 month of potent P2Y12 inhibitor based DAPT.	Drug: P2Y12 antagonist monotherapy; CYP2C19 genetic testing is performed before discharge after stent insertion. Depending on the test results, rapid (CYP2C19*1/*17 or *17/*17) or normal (CYP2C19*1/*1) metabolizers are treated with clopidogrel monotherapy, and intermediate or poor metabolizers (with CYP2C19*2 or *3 alleles) are treated with potent P2Y12 inhibitors (prasugrel or ticagrelor) monotherapy.
Active Comparator: Un-guided de-escalation of DAPT; A potent P2Y12 inhibitor is changed to clopidogrel 1 month after PCI, and aspirin is maintained.	Drug: clopidogrel + aspirin; In this group, a potent P2Y12 inhibitor was changed to clopidogrel (un-guided) 1 month after PCI with maintenance of co-prescription of aspirin (DAPT).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major or clinically relevant non-major bleeding	Bleeding Academic Research Consortium type 2, 3, or 5	6 months after PCI

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major bleeding	BARC type 3 or 5	6 months after PCI
Clinically relevant non-major bleeding	BARC type 2	6 months after PCI
Net adverse clinical event	A composite of all-cause death, MI, stroke, stent thrombosis, and major bleeding	6 months after PCI
Major adverse cardiac and cerebrovascular event	A composite of all-cause death, MI, stent thrombosis, or stroke	6 months after PCI
All-cause death	Death from any causes	6 months after PCI
Cardiovascular death	Death from cardiovascular causes	6 months after PCI
MI		6 months after PCI
Stent thrombosis	Definite or probable, defined by ARC	6 months after PCI
Stroke		6 months after PCI
Repeat revascularization		6 months after PCI
Target vessel revascularization		6 months after PCI
Target lesion revascularization		6 months after PCI
A composite of cardiovascular death, MI, stent thrombosis, or stroke		6 months after PCI
A composite of cardiovascular death, MI, stent thrombosis, stroke, or repeat revascularization		6 months after PCI
Total medical cost		1 year after PCI
Major or clinically relevant non-major bleeding		1 year after PCI
Major bleeding		1 year after PCI
Clinically relevant non-major bleeding		1 year after PCI
Net adverse clinical event	A composite of all-cause death, MI, stent thrombosis, stroke, and major bleeding	1 year after PCI
Major adverse cardiac and cerebrovascular event	A composite of all-cause death, MI, stent thrombosis, or stroke	1 year after PCI
All-cause death		1 year after PCI
Cardiovascular death		1 year after PCI
MI		1 year after PCI
Stroke		1 year after PCI
Repeat revascularization		1 year after PCI
Target vessel revascularization		1 year after PCI
Target lesion revascularization		1 year after PCI
A composite of cardiovascular death, MI, stent thrombosis, or stroke		1 year after PCI
A composite of cardiovascular death, MI, stent thrombosis, stroke, or repeat revascularization		1 year after PCI
Stent thrombosis		1 year after PCI

Collaborators and Investigators

• Sponsor: Samsung Medical Center
• Investigators: Principal Investigator: Joo-Yong Hahn, MD, PhD, Samsung Medical Center

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2025
• Primary Completion (Estimated): July 31, 2029
• Study Completion (Estimated): December 31, 2029

Study Registration Dates

• First Submitted: January 1, 2025
• First Submitted That Met QC Criteria: January 1, 2025
• First Posted (Actual): January 8, 2025

Study Record Updates

• Last Update Posted (Actual): May 18, 2025
• Last Update Submitted That Met QC Criteria: May 14, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: Acute coronary syndrome; High bleeding risk; De-escalation therapy; CYP2C19 Genotype; P2Y12 inhibitor monotherapy
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Disease; Myocardial Ischemia; Syndrome; Hemorrhage; Acute Coronary Syndrome; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Fibrin Modulating Agents; Antirheumatic Agents; Sensory System Agents; Analgesics, Non-Narcotic; Analgesics; Antipyretics; Neurotransmitter Agents; Anti-Inflammatory Agents, Non-Steroidal; Cyclooxygenase Inhibitors; Fibrinolytic Agents; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Clopidogrel; Aspirin
• Other Study ID Numbers: GUIDE-HBR

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