Clinical trial NCT05818475: Functional Coronary Angiography Guided Revascularization in STEMI
Official title: Functional Coronary Angiography to Indicate and Guide Revascularization in STEMI Patients with Multivessel Disease
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Myocardial Infarction
Keywords: Percutaneous coronary intervention
Angiography-derived Fractional Flow Reserve
Multivessel disease
Lead sponsor: University Hospital of Ferrara
Sponsor class: OTHER
First posted: 2023-04-18
Enrollment: 1823
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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:

1. It is possible to acquire projection during primary PCI and perform the analysis off-line
2. In case of negative assessment, the patient can avoid a second procedure to invasively measure physiology
3. 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.
4. 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.

Eligibility criteria: 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)

Primary outcomes:
measure: Primary Efficacy Outcome: Patient Oriented Composite Outcome
timeFrame: through study completion, an average of 18 months
measure: Primary Safety Outcome: Major Bleeding and Contrast - Associated Acute Kidney Injury
timeFrame: through study completion, an average of 18 months
Secondary outcomes:
measure: Main Secondary Outcome: Cardiovascular Mortality and Myocardial Infarction
timeFrame: through study completion, an average of 18 months
Other outcomes:
Locations:
city: Bologna
country: Italy
facility: AUSL Bologna Ospedale Maggiore
state: BO
city: Ferrara
country: Italy
facility: Azienda Ospedaliero Universitaria di Ferrara
state: FE
city: Baggiovara
country: Italy
facility: Ospedale Civile di Baggiovara
state: MO
city: Piacenza
country: Italy
facility: AUSL Piacenza
state: PC
city: Parma
country: Italy
facility: Azienda Ospedaliero Universitaria di Parma
state: PR
city: Reggio Emilia
country: Italy
facility: Arcispedale Santa Maria Nuova di Reggio Emilia
state: RE
city: Rimini
country: Italy
facility: AUSL Romagna Ospedale degli Infermi Rimini
state: RN
city: Rovigo
country: Italy
facility: Ospedale Santa Maria della Misericordia Rovigo
state: RO
city: Mestre
country: Italy
facility: Ospedale dell'Angelo Mestre
state: VE
city: Legnago
country: Italy
facility: Ospedale Mater Salutis Legnago
state: VR
city: Verona
country: Italy
facility: Azienda Ospedaliero Universitaria Integrata di Verona
state: VR
city: Bergamo
country: Italy
facility: ASST Papa Giovanni XXIII
city: Bolzano
country: Italy
facility: Ospedale di Bolzano
city: Caserta
country: Italy
facility: AORN Sant'Anna e San Sebastiano
city: Catanzaro
country: Italy
facility: Azienda Ospedaliero Universitaria Mater Domini
city: Cosenza
country: Italy
facility: Ospedale Annunziata
city: Latina
country: Italy
facility: Ospedale Santa Maria Goretti
city: Novara
country: Italy
facility: Ospedale Maggiore della Carità Novara
city: Pisa
country: Italy
facility: Azienda Ospedaliero Universitaria Pisana
city: Ravenna
country: Italy
facility: AUSL Romagna Santa Maria delle Croci Ravenna
city: Roma
country: Italy
facility: Policlinico Casilino
city: Karachi
country: Pakistan
facility: NICVD Karachi
Study officials:
References:
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citation: Puymirat E, Cayla G, Simon T, Steg PG, Montalescot G, Durand-Zaleski I, le Bras A, Gallet R, Khalife K, Morelle JF, Motreff P, Lemesle G, Dillinger JG, Lhermusier T, Silvain J, Roule V, Labeque JN, Range G, Ducrocq G, Cottin Y, Blanchard D, Charles Nelson A, De Bruyne B, Chatellier G, Danchin N; FLOWER-MI Study Investigators. Multivessel PCI Guided by FFR or Angiography for Myocardial Infarction. N Engl J Med. 2021 Jul 22;385(4):297-308. doi: 10.1056/NEJMoa2104650. Epub 2021 May 16.
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