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

Официальное название

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)

Обзор

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).

Подробное описание

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.

Вмешательства

• Препарат 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.
• Препарат 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).

Первичные конечные точки

• Major or clinically relevant non-major bleeding [Срок оценки: 6 months after PCI]

Вторичные конечные точки (12)

• Major bleeding [Срок оценки: 6 months after PCI]
• Clinically relevant non-major bleeding [Срок оценки: 6 months after PCI]
• Net adverse clinical event [Срок оценки: 6 months after PCI]
• Major adverse cardiac and cerebrovascular event [Срок оценки: 6 months after PCI]
• All-cause death [Срок оценки: 6 months after PCI]
• Cardiovascular death [Срок оценки: 6 months after PCI]
• MI [Срок оценки: 6 months after PCI]
• Stent thrombosis [Срок оценки: 6 months after PCI]
• Stroke [Срок оценки: 6 months after PCI]
• Repeat revascularization [Срок оценки: 6 months after PCI]
• Target vessel revascularization [Срок оценки: 6 months after PCI]
• Target lesion revascularization [Срок оценки: 6 months after PCI]

Критерии участия

Критерии включения

• 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)

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

South Korea · 1 центр

• Samsung Medical Center — Seoul

Идентификаторы

NCT: NCT06763744 · GUIDE-HBR

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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