Acute Coronary Syndrome (ACS) Undergoing Percutaneous Coronary Intervention (PCI), High Bleeding Risk
Conditions
Keywords
CYP2C19 Genotype, Acute coronary syndrome, De-escalation therapy, P2Y12 inhibitor monotherapy, High bleeding risk
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.
Interventions
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.
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).
Sponsors
Samsung Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Prospective, open-label, two-arm, randomized controlled trial
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Major or clinically relevant non-major bleeding | 6 months after PCI | Bleeding Academic Research Consortium type 2, 3, or 5 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinically relevant non-major bleeding | 6 months after PCI | BARC type 2 |
| Net adverse clinical event | 6 months after PCI | A composite of all-cause death, MI, stroke, stent thrombosis, and major bleeding |
| Major adverse cardiac and cerebrovascular event | 6 months after PCI | A composite of all-cause death, MI, stent thrombosis, or stroke |
| All-cause death | 6 months after PCI | Death from any causes |
| Cardiovascular death | 6 months after PCI | Death from cardiovascular causes |
| MI | 6 months after PCI | — |
| Stent thrombosis | 6 months after PCI | Definite or probable, defined by ARC |
| Major bleeding | 6 months after PCI | BARC type 3 or 5 |
| 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 | — |
| Stroke | 6 months after PCI | — |
Countries
South Korea
Contacts
Primary ContactJoo-Yong Hahn, MD, PhD
Backup ContactKi Hong Choi, MD, PhD
Outcome results
None listed