A Precision Medicine Approach to Identify Patients Undergoing Elective PCI at Risk of Peri-PCI Myocardial Infarction

Study Overview
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Brief Summary
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Despite the relative safety of PCI with new generation stents, peri-PCI thrombotic complications, including myocardial infarction and myocardial injury, are common in elective PCI, occurring in up to 30% of patients. Importantly, these events are associated with poor prognosis. The risk of peri-PCI myocardial infarction/myocardial injury has been in part attributed to HPR. The aim of this study is to prospectively validate the accuracy of the ABCD-GENE score in identifying stable CAD patients undergoing elective PCI treated with standard of care clopidogrel who are at risk of peri-PCI myocardial infarction/myocardial injury. This investigation will be a prospective cohort study conducted in a population of patients (n=500) with stable CAD undergoing elective PCI treated with standard of care clopidogrel. By integrating genetic data with clinical variables, patients will be stratified into 2 cohorts based on their ABCD-GENE score (using a cut-off of 10). Assessments to define HPR status and myocardial infarction/myocardial injury will be performed post-PCI.

Detailed Description
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Antiplatelet therapy with aspirin and a P2Y12 inhibitor is the cornerstone of treatment for patients undergoing percutaneous coronary intervention (PCI). Clopidogrel is the recommended P2Y12 inhibitor in patients with stable coronary artery disease (CAD) undergoing elective PCI. However, clopidogrel effects are subject to variability and 30-40% of patients have high platelet reactivity (HPR), which translates into higher rates of thrombotic complications. Despite the relative safety of PCI with new generation stents, peri-PCI thrombotic complications, including myocardial infarction and myocardial injury, are common in elective PCI, occurring in up to 30% of patients. Importantly, these events are associated with poor prognosis. The risk of peri-PCI myocardial infarction/myocardial injury has been in part attributed to HPR. The investigators recently developed a precision medicine tool integrating clinical and genetic factors called ABCD-GENE able to identify HPR status. This score helps characterize patients at risk for peri-PCI thrombotic complications, who can thus potentially benefit from changes in antiplatelet treatment regimen. However, the ABCD-GENE score was generated through retrospective assessments, thus warranting prospective validation. The high frequency of elective PCI procedures and the prevalence with which myocardial infarction/myocardial injury occurs underscore the need for tools that can better identify patients at risk so that therapeutic measures can be implemented to improve their prognosis. The aim of this study is to prospectively validate the accuracy of the ABCD-GENE score in identifying stable CAD patients undergoing elective PCI treated with standard of care clopidogrel who are at risk of peri-PCI myocardial infarction/myocardial injury. This investigation will be a prospective cohort study conducted in a population of patients (n=500) with stable CAD undergoing elective PCI treated with standard of care clopidogrel. By integrating genetic data with clinical variables, patients will be stratified into 2 cohorts based on their ABCD-GENE score (using a cut-off of 10). Assessments to define HPR status and myocardial infarction/myocardial injury will be performed post-PCI.

Official Title
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Ability of a Precision Medicine Approach to Identify Stable CAD Patients Undergoing Elective PCI Who Are at Risk of Peri-PCI Myocardial Infarction/Myocardial Injury: The ABCD-Gene Prospective Study

Conditions
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Coronary Artery Disease

Intervention / Treatment
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* Diagnostic Test: Assessment of platelet reactivity
* Diagnostic Test: Troponin measurement


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Stable CAD undergoing elective PCI; Male or females, Age ≥ 18 years old; Troponin negative before PCI*; Background of aspirin therapy; If troponin is unknown before coronary angiography and no clinical signs of acute coronary syndrome is present, a troponin will not be collected as this is line with standard practice. Exclusion criteria: Current presentation with myocardial infarction; On treatment with prasugrel or ticagrelor; Documented hypersensitivity to clopidogrel; Use of an intravenous antiplatelet therapy (i.e., cangrelor or GPI) during PCI; Unable to provide written informed consent.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| High ABCD-GENE score (≥10)<br>All patients in this cohort will have an ABCD-GENE score ≥10 and will be receiving clopidogrel following PCI as per standard of care. The ABCD-GENE score encompasses a total of 5 variables: 4 clinical (age, body mass index, chronic kidney disease status, and diabetes mellitus) and 1 genetic (CYP2C19 LOF). | Diagnostic Test: Assessment of platelet reactivity<br>* Assessment of platelet reactivity and HPR status will be performed post-PCI. Platelet reactivity will be measured by VerifyNow P2Y12 and HPR status will be defined using a cut-off value of platelet reactivity units (PRU)>208.<br>Diagnostic Test: Troponin measurement<br>* Measurement of high sensitivity troponin for the assessment for the presence of myocardial infarction/myocardial injury will be performed post-PCI.<br>|
| Low ABCD-GENE score (<10)<br>All patients in this cohort will have an ABCD-GENE score <10 and will be receiving clopidogrel following PCI as per standard of care. The ABCD-GENE score encompasses a total of 5 variables: 4 clinical (age, body mass index, chronic kidney disease status, and diabetes mellitus) and 1 genetic (CYP2C19 LOF). | Diagnostic Test: Assessment of platelet reactivity<br>* Assessment of platelet reactivity and HPR status will be performed post-PCI. Platelet reactivity will be measured by VerifyNow P2Y12 and HPR status will be defined using a cut-off value of platelet reactivity units (PRU)>208.<br>Diagnostic Test: Troponin measurement<br>* Measurement of high sensitivity troponin for the assessment for the presence of myocardial infarction/myocardial injury will be performed post-PCI.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peri-PCI myocardial infarction or myocardial injury | The primary endpoint of the study will be rate of peri-PCI myocardial infarction or myocardial injury, which will be compared between the high ABCD-GENE score cohort and the low ABCD-GENE score cohort. | 24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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percutaneous coronary intervention, clopidogrel, high platelet reactivity, myocardial injury