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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).
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Genotype-guided abbreviated DAPT | Active Comparator | 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 | Active Comparator | A potent P2Y12 inhibitor is changed to clopidogrel 1 month after PCI, and aspirin is maintained. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| P2Y12 antagonist monotherapy | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Major or clinically relevant non-major bleeding | Bleeding Academic Research Consortium type 2, 3, or 5 | 6 months after PCI |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Joo-Yong Hahn, MD, PhD | Contact | 82-2-3410-3419 | jyhahn@skku.edu | |
| Ki Hong Choi, MD, PhD | Contact | 82-2-3410-6653 | cardiokh@gmail.com |
| Name | Affiliation | Role |
|---|---|---|
| Joo-Yong Hahn, MD, PhD | Samsung Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Samsung Medical Center | Seoul | 06351 | South Korea |
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Prospective, open-label, two-arm, randomized controlled trial
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|
| clopidogrel + aspirin | Drug | 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). |
|
| 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 |
| Stent thrombosis | 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 |
| ID | Term |
|---|---|
| D054058 | Acute Coronary Syndrome |
| ID | Term |
|---|---|
| D017202 | Myocardial Ischemia |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D014652 | Vascular Diseases |
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| ID | Term |
|---|---|
| D000077144 | Clopidogrel |
| D001241 | Aspirin |
| ID | Term |
|---|---|
| D013988 | Ticlopidine |
| D058924 | Thienopyridines |
| D013876 | Thiophenes |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
| D011725 | Pyridines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D012459 | Salicylates |
| D062385 | Hydroxybenzoates |
| D010636 | Phenols |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
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