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

Samsung Medical Center

Status and phase: Not yet enrolling; Phase 4

Conditions: High Bleeding Risk; Acute Coronary Syndrome (ACS) Undergoing Percutaneous Coronary Intervention (PCI)

Treatments: Drug: P2Y12 antagonist monotherapy; Drug: clopidogrel + aspirin

Study type: Interventional

Funder types: Other

Identifiers

NCT06763744

GUIDE-HBR

Details and patient eligibility

About

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).

Full 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.

Enrollment: 3,000 estimated patients

Sex: All

Ages: 19+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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3,000 participants in 2 patient groups

Genotype-guided abbreviated DAPT

Active Comparator group

Description:

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.

Treatment:

Drug: P2Y12 antagonist monotherapy

Un-guided de-escalation of DAPT

Active Comparator group

Description:

A potent P2Y12 inhibitor is changed to clopidogrel 1 month after PCI, and aspirin is maintained.

Treatment:

Drug: clopidogrel + aspirin