Angiographic Control vs. Ischemia-driven Management of Patients Treated With PCI on Left Main With Drug-eluting Stents

Study Overview
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Brief Summary
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The present study aims to compare a planned angiographic control (PAC) follow-up strategy vs. conservative management for patients treated with drug-eluting stents on unprotected left main artery in a prospective, randomized setting. PAC will be performed by coronary computed tomography (CCT), to avoid the limitations of the invasive coronary angiography which is usually employed to perform PAC. The superiority of a PAC-based approach will be tested on a hard clinical end-point such as the incidence of major adverse cardiovascular events. The investigators will also assess the performance of CCT as a tool to perform PAC.

Detailed Description
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Given the undefined picture surrounding the appropriateness of planned angiographic control (PAC) following percutaneous coronary intervention (PCI) of the unprotected left main (ULM) with drug-eluting stents (DES), our aim is to evaluate, in a prospective, randomized, setting, the potential benefits of a PAC-based strategy vs. ischemia and symptoms driven conservative management. The disease of the native ULM is associated with an unfavorable prognostic outcome, which can be at least partially reversed by revascularization. Significant stenosis of the stented ULM caused by in-stent restenosis (ISR), however, presents some peculiar pathophysiological, flow-related and shear-stress features, which partly makes it a distinct disease as compared to native vessel atherosclerosis. Treatment of ISR, moreover, is a scarcely standardized and often complex procedure; some uncertainties still persist regarding the best strategy to treat ISR (stent-in-stent, drug-eluting balloons, dilation with conventional balloons). Computed coronary tomography (CCT) can precisely and not-invasively assess the presence of ISR in the stented ULM, without exposing the patients to the risks of invasive catheterization. CCT may provide an accurate reconstruction of the stented vessels, exposing the patients to a limited amount of contrast dye (approximately, 80-100 cc) and of radiation dose (approximately, 92 mGy). CCT has a very high negative predictive value for ISR, thus limiting the negative impact of the indiscriminate execution of invasive angiography on all patients treated by PCI of the ULM. Only patients with relevant ISR of ULM at CCT will undergo coronary angiography to confirm the presence of critical stenosis, and fractional flow reserve (FFR) and/or intravascular ultrasound (IVUS) will be performed in dubious cases. An increased rate of PCI has to be taken in to account with a PAC-based approach. However, with the accurate, stepwise selection of the patients and the lesions amenable to PCI of our study protocol, based on CCT, coronary angiography and, where necessary, FFR/IVUS, the increased rate of PCI is not expected to bear a negative prognostic impact. Based on these premises, our hypothesis is that early, appropriate, detection of ULM ISR and its subsequent treatment may positively impact patients' survival and reduce the incidence of adverse cardiovascular events. Specific aim 1: Evaluation of the effectiveness and safety of a PAC-based approach to follow-up patients treated by PCI of the ULM with DES-II Specific aim 2: Assessment of the incidence of ISR in patients undergoing PCI of the ULM with DES-II and evaluation of the diagnostic accuracy of CCT in the evaluation of ISR in the stented ULM Specific Aim 3: Assessment of the prognostic implications and safety of the PCI of ISR of the ULM detected by PAC as compared to conservative management with revascularization driven by symptoms and ischemia. For this purpose in this prospective, randomized controlled trial (RCT), patients will be enrolled following the index percutaneous revascularization of ULM with DES. Patients will be randomized in a 1:1 fashion to PAC-based management with CCT vs. symptoms and ischemia driven conservative management.

Official Title
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Angiographic Control vs. Ischemia-driven Management of Patients Undergoing Percutaneous Revascularization of the Unprotected Left Main Coronary Artery With Second-generation Drug Eluting Stents: the PULSE Trial

Conditions
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Acute Coronary Syndrome, Stable Chronic Angina, Coronary Artery Disease, Left Main Coronary Artery Disease

Intervention / Treatment
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* Diagnostic Test: coronary computed tomography


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with ULM disease treated by PCI with DES-II with the following inclusion criteria: Age 18-85. Glomerular filtration rate > 30 ml/min Indication to percutaneous revascularization of ULM according to Syntax score (< 33) or, in dubious cases, after Heart Team evaluation Exclusion Criteria: Cardiogenic shock Refusal or inability to provide informed consent

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: coronary computed tomography<br> | Diagnostic Test: coronary computed tomography<br>* patients randomized in this arm will perform computed coronary tomography 6 months after the index percutaneous revascularization on unprotected left main artery<br>|
| No Intervention: conservative (ischemia-guided) management<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major adverse cardiovascular events (MACE) | composite and mutual exclusive end point including death, cardiovascular death, myocardial infarction (MI) (excluding periprocedural MI), unstable angina (UA), stent thrombosis | 18 months after the index revascularization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Target lesion revascularization (TLR) | target lesion revascularization including any TLR, any unplanned TLR and TLR driven by PAC | 18 months after the index revascularization | 
| All cause death | death from any cause occurring during follow up | within 18 months from the index revascularization | 
| stent thrombosis | Any stent thrombosis (definite, probable or possible) | within 18 months from the index revascularization | 
| CV death | death from cardiovascular causes | within 18 months from the index revascularization | 
| Myocardial infarction | Myocardial infarction defined as non ST elevation acute coronary syndrome (NST-ACS) or ST elevation myocardial infarction (STEMI) | within 18 months from the index revascularization |