Clinical Evidence With Biomarker Confirmation for PPMI in PCI Clinical Trials Study

Periprocedural myocardial infarction (PPMI) is commonly included as an outcome in clinical trials involving percutaneous coronary intervention (PCI). However, uncertainty remains regarding the most appropriate cardiac biomarker, biomarker threshold, and accompanying clinical criteria to use when defining PPMI. The increasing use of high-sensitivity troponin assays has further complicated the interpretation of cardiac biomarker elevations after PCI. Lower biomarker thresholds may identify a relatively large proportion of patients, but the clinical significance of these elevations and their relationship with subsequent adverse outcomes remain uncertain.

Several definitions of PPMI are currently used, including the Fourth Universal Definition of Myocardial Infarction, the Academic Research Consortium-2 (ARC-2) definition, and the Society for Cardiovascular Angiography and Interventions (SCAI) definition. These definitions differ in their required biomarker thresholds and in how clinical evidence of periprocedural ischemia is incorporated. In addition, routine collection of serial post-PCI biomarkers can be challenging in contemporary practice, particularly because many patients are discharged on the same day as their procedure. Differences among cardiac biomarkers, including troponin I, troponin T, and creatine kinase-myocardial band (CK-MB), may also affect the frequency with which PPMI is diagnosed.

CEC-PPMI is a prospective, multicenter, non-randomized cohort study designed to evaluate the relationship among clinical evidence of periprocedural ischemia, cardiac biomarker elevation after PCI, and adverse clinical outcomes at one year. The study will enroll up to 1,000 adults at up to 20 clinical sites in the United States. An adaptive enrollment design will be used to ensure that at least 250 participants have positive clinical criteria.

Eligible participants will have stable coronary artery disease, including stable angina or functional evidence of ischemia, or stabilized non-ST-elevation acute coronary syndrome, and will be undergoing PCI. The PCI procedure will be performed according to local standards of care using commercially approved devices or devices being evaluated under an applicable investigational device exemption. The study does not assign a specific PCI device, treatment strategy, or medical therapy. The study will not analyze outcomes according to a specific device or manufacturer.

Before PCI, participants will provide informed consent. Baseline demographic information, clinical characteristics, and procedural and lesion-related information will also be collected.

All participants will have cardiac biomarker samples collected before PCI and approximately 4 to 6 hours after PCI. Participants who remain hospitalized will have an additional sample collected approximately 12 to 24 hours after PCI. All samples will be sent to and analyzed at a central laboratory for CK-MB, troponin T, and troponin I. Centralized analysis will allow direct comparison of these biomarkers using samples collected at the same time, with each participant serving as a matched control.

After PCI, the study team will complete a clinical criteria checklist. The checklist will identify clinical evidence potentially consistent with periprocedural myocardial ischemia, including relevant symptoms, electrocardiographic findings, and angiographic complications. The study team will also document whether the participant is planned for same-day discharge or hospitalization for at least one night.

Baseline lesion characteristics and PCI-related angiographic findings will be evaluated by an independent angiographic core laboratory. Assessments will include lesion length, bifurcation involvement, thrombus, percentage diameter stenosis, dissection, side-branch occlusion, distal embolization, and slow coronary flow. Agreement between clinical-site reporting and independent core-laboratory assessment of angiographic complications will be examined.

Participants will be categorized according to the result of the clinical criteria checklist and their planned post-PCI disposition. The four prespecified groups are:

• Negative clinical criteria and same-day discharge.
• Negative clinical criteria and hospitalization.
• Positive clinical criteria and same-day discharge.
• Positive clinical criteria and hospitalization. The primary endpoint is elevation of troponin I or troponin T to greater than five times the assay-specific upper reference limit following PCI, based on central laboratory measurements. The primary comparison will evaluate the frequency of this biomarker elevation among participants with positive clinical criteria compared with participants with negative clinical criteria.

The key secondary endpoint is the composite of all-cause mortality or hospitalization for heart failure at one year. This outcome will be compared between participants with positive and negative clinical criteria. The individual components of the composite endpoint will also be evaluated.

Additional analyses will examine:

• The distribution and magnitude of troponin I and troponin T elevations after PCI.
• The relationship between different biomarker thresholds and one-year all-cause mortality or hospitalization for heart failure.
• Differences in biomarker elevations and clinical outcomes between participants planned for same-day discharge and those planned for hospitalization.
• The frequency of PPMI according to the Fourth Universal Definition of Myocardial Infarction, ARC-2, and SCAI definitions.
• Differences in the frequency of PPMI according to the biomarker used, including troponin I, troponin T, and CK-MB.
• The effect of positive or negative clinical criteria on the relationship between post-PCI biomarker elevation and one-year clinical outcomes.
• The association between elevated baseline biomarker levels and one-year all-cause mortality or hospitalization for heart failure.
• The correlation among CK-MB, troponin T, and troponin I based on central laboratory measurements.
• Agreement between clinical-site and angiographic core-laboratory reporting of PCI-related complications.
• Whether participants with negative clinical criteria and planned same-day discharge represent a low-risk group with a reduced incidence of adverse clinical outcomes at one year.

Follow-up at one year to assess vital status and whether hospitalization for heart failure has occurred will be completed using a direct-to-participant remote approach. If contact with the participant is unsuccessful, an alternate contact will be approached. If this is also unsuccessful, a series of additional follow-up methods, as permitted by the participant's consent and applicable requirements, will be used to ascertain the secondary endpoint.

The study is intended to clarify whether a standardized, clinically driven assessment can help identify patients at increased risk for meaningful cardiac biomarker elevation after PCI and whether combining clinical criteria with specific biomarker thresholds improves the identification of patients at risk for adverse outcomes. The findings may also inform future definitions of PPMI and reduce the burden and missing data associated with routine serial biomarker collection in PCI clinical trials.