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

Phase 4

Not yet recruiting

• Conditions: Acute Coronary Syndrome (ACS) Undergoing Percutaneous Coronary Intervention (PCI); High Bleeding Risk
• Interventions: Drug: P2Y12 antagonist monotherapy; Drug: clopidogrel + aspirin

• Registration Number: NCT06763744
• Lead Sponsor: Samsung Medical Center

Brief Summary

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).

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 Timeline

• Study First Submitted: 2025-01-01
• Study First Submitted QC: 2025-01-01
• Study First Posted: 2025-01-08
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-14
• Last Update Posted: 2025-05-18
• Study Start: 2025-06-01
• Primary Completion: 2029-07-31
• Study Completion: 2029-12-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 3000

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Genotype-guided abbreviated DAPT	P2Y12 antagonist monotherapy	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.
Un-guided de-escalation of DAPT	clopidogrel + aspirin	A potent P2Y12 inhibitor is changed to clopidogrel 1 month after PCI, and aspirin is maintained.

Primary Outcome Measures

Name	Time	Method
Major or clinically relevant non-major bleeding	6 months after PCI	Bleeding Academic Research Consortium type 2, 3, or 5

Secondary Outcome Measures

Name	Time	Method
Net adverse clinical event	1 year after PCI	A composite of all-cause death, MI, stent thrombosis, stroke, and major bleeding
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
Total medical cost	1 year after PCI
Major or clinically relevant non-major bleeding	1 year after PCI
All-cause death	1 year after PCI
Cardiovascular death	1 year after PCI
Clinically relevant non-major bleeding	1 year after PCI
Major bleeding	1 year after PCI
MI	1 year after PCI
Stent thrombosis	1 year after PCI
Major adverse cardiac and cerebrovascular event	1 year after PCI	A composite of all-cause death, MI, stent thrombosis, or stroke

Trial Locations

Locations (1)

Samsung Medical Center; 🇰🇷 Seoul, Korea, Republic of