Functional Coronary Angiography Guided Revascularization in STEMI

Study Overview
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Brief Summary
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The goal of this multicenter randomized clinical trial is to test the superiority in terms of efficacy of the Angiography-derived fractional flow reserve (AIR) over that based on conventional angiography (ANGIO) strategy in the management of non-culprit lesions in STEMI patients with multivessel disease. The main questions it aims to answer are: is an Angiography-derived fractional flow reserve strategy superior to a conventional angiography strategy in reducing the occurrence of the composite efficacy endpoint of all-cause death, myocardial infarction, cerebrovascular accident, or ischemia-driven revascularization. is an Angiography-derived fractional flow reserve strategy superior to a conventional angiography strategy in reducing the occurrence of the composite safety endpoint of of contrast-associated acute kidney injury and Bleeding Academic Research Consortium (BARC) type 3-5. Participants will be randomized after the successful treatment of the culprit lesion to one of the two strategies and prospectively followed-up.

Detailed Description
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Reperfusion of the culprit lesion through primary PCI is the standard of care in ST-segment elevation myocardial infarction (STEMI) patients, regardless of their age. The actual gold standard for the management of non-culprit lesions in STEMI patients with multivessel disease (MVD) is angiography-guided complete revascularization. The Complete vs Culprit-only Revascularization to Treat Multi-vessel Disease after Primary PCI for STEMI (COMPLETE) trial randomized 4 041 patients with STEMI and MVD. The main finding was the highly significant reduction of new MI occurrence in the complete group (7.9% vs 5.4%, hazard ratio (HR) 0.68, 95% CI 0.53-0.87, p=0.002). Revascularization was obtained largely by angiographic evaluation (>99%). After COMPLETE, the subsequent step was to ascertain which complete revascularization strategy should be pursued. In particular, physiology-guided revascularization was compared to an angio-guided strategy. The advantages of physiology against angiography are related to: a) lower number of vessels treated, b) lower number of stents implanted; c) avoidance of a second procedure in negative fractional flow reserve (FFR) patients during primary PCI; d) possibility to optimize the procedure from the physiological standpoint after percutaneous coronary intervention (PCI). In the Flow Evaluation to Guide Revascularization in Multivessel ST-Elevation Myocardial Infarction (FLOWER-MI), patients with STEMI and multivessel disease who had undergone successful PCI of the infarct-related artery were randomly assigned to receive complete revascularization guided by either FFR or angiography. The primary outcome was a composite of death from any cause, nonfatal myocardial infarction, or unplanned hospitalization leading to urgent revascularization at 1 year. FFR-guided revascularization was associated with lower number of stents implanted per patient (1.01±0.99 versus 1.50±0.86). During follow-up, a primary outcome event occurred in 32 of 586 patients (5.5%) in the FFR-guided group and in 24 of 577 patients (4.2%) in the angiography-guided group (hazard ratio, 1.32; 95% confidence interval, 0.78 to 2.23; P = 0.31). Death occurred in 9 patients (1.5%) in the FFR-guided group and in 10 (1.7%) in the angiography-guided group; nonfatal myocardial infarction in 18 (3.1%) and 10 (1.7%), respectively; and unplanned hospitalization leading to urgent revascularization in 15 (2.6%) and 11 (1.9%), respectively. The results of the FLOWER-MI trial may suggest that physiology can provide a similar outcome if compared to a conventional angio-guided approach. However, some limitation should be acknowledged: i) rate of events was three-times lower than expected suggesting both a selection bias and the need of a higher number of patients to demonstrate any difference among the two groups; ii) all patients in the FFR-group received a staged procedure to perform physiology assessment diluting one of the major advantages in FFR negative patients, namely the avoidance of a second procedure if physiology is negative; iii) in 16% of patients in the physio-guided group FFR was not performed before PCI, whereas in 82% of patients it was not performed after PCI; iv) even if FFR was associated with lower PCIs, periprocedural MI was three times higher if compared to the angio-group, suggesting its possible underreporting in the angio-group. After the COMPLETE trial2, the actual standard of care in the management of STEMI patients with MVD is complete revascularization based on angiography. However, this approach may lead to over- or under-estimation of lesions in a relevant portion of patients with negative impact on prognosis. Invasive physiology has been consistently shown to be superior if compared to angio-guided strategy, but it is underutilized in clinical practice mainly due to feasibility issues. A functional coronary angiography could overcome the applicability issues related to invasive physiology. In addition, it is particularly appealing in the evaluation of non-culprit lesions since: It is possible to acquire projection during primary PCI and perform the analysis off-line In case of negative assessment, the patient can avoid a second procedure to invasively measure physiology It is possible to optimize most of the procedures by the physiological standpoint through the utilization of the virtual-PCI planner tool pre-PCI without the need to repeat physiology after PCI. It has been recently shown that if compared to an angio-guided approach, Angiography-derived FFR was able to reduce the incidence of spontaneous MI by 36% Therefore, a strategy based on functional coronary angiography to indicate and guide PCI could be superior if compared to an angio-guided strategy both from the efficacy (CV death, cerebrovascular accident, MI and ischemia-driven revascularization) and from the safety (BARC 3-5, contrast-associated acute kidney injury) standpoint.

Official Title
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Functional Coronary Angiography to Indicate and Guide Revascularization in STEMI Patients With Multivessel Disease

Conditions
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Myocardial Infarction

Intervention / Treatment
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* Other: Angiography-guided PCI
* Other: Angiography-derived FFR PCI indication and planning


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ST-segment elevation myocardial infarction with indication to invasive management Multi-vessel disease defined as at least 1 non-culprit coronary artery lesion at least 2.5 mm in diameter deemed at visual estimation with a diameter stenosis % ranging from 50 to 99% amenable to successful treatment with PCI Successful treatment of culprit lesion Exclusion Criteria: Planned surgical revascularization Left main as non-culprit lesion Non-cardiovascular co-morbidity reducing life expectancy to < 1 year Any factor precluding 1-year follow-up Prior Coronary Artery Bypass Graft (CABG) Surgery Impossibility to identify a clear culprit lesion Presence of a chronic total occlusion (CTO)

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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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Angiography-guided PCI<br>Patients will receive PCI of all lesions with at least 50% diameter stenosis at visual estimation. PCI plan and assessment of PCI results will be based on angiography. | Other: Angiography-guided PCI<br>* Non-culprit lesion treatment will be based on visual estimation by angiography. The evaluation of PCI result will be also based only on angiography.<br>|
| Experimental: Angiography-derived FFR PCI indication and planning<br>Patients will receive PCI of all lesions with at least 50% diameter stenosis and positive angiography-derived FFR value (≤0.80). PCI planning will be based on the pullback curve obtained by angiography-derived FFR to obtain an optimal post-PCI physiology. | Other: Angiography-derived FFR PCI indication and planning<br>* Non-culprit lesion treatment will be based on angiography-derived FFR result. In case of positive assessment, PCI will be planned according to the virtual PCI plan based on the physiology pullback curve.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Efficacy Outcome: Patient Oriented Composite Outcome | Cumulative occurrence of mortality, cerebrovascular accident, reinfarction, or ischemia-driven revascularization | through study completion, an average of 18 months | 
| Primary Safety Outcome: Major Bleeding and Contrast - Associated Acute Kidney Injury | Cumulative occurrence of contrast-associated acute kidney injury and bleeding BARC 3-5 | through study completion, an average of 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Main Secondary Outcome: Cardiovascular Mortality and Myocardial Infarction | Cumulative occurrence of cardiovascular mortality and myocardial infarction | through study completion, an average of 18 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Percutaneous coronary intervention, Angiography-derived Fractional Flow Reserve, Multivessel disease