FIRE: Functional Assessment in Elderly MI Patients With Multivessel Disease

Sponsor

Consorzio Futuro in Ricerca (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT03772743

Collaborator

(none)

1,445

Enrollment

Locations

Arms

85.6

Anticipated Duration (Months)

49.8

Patients Per Site

0.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Elderly patients presenting with myocardial infarction (MI) and multivessel disease are the highest risk population with the worst prognosis. No trial has ever been designed to optimize their outcome. The actual real-life standard of care is, in the best of the cases, culprit only revascularization. However, real-life registries show that outcome of MI elderly patients treated with this strategy is far from being optimal with at least a 15% rate of cardiac death or myocardial infarction at 1 year. To date, studies on this population have been focused on devices (bare metal stent vs biodegradable drug eluting stent) or on dual antiplatelet regimen (long vs short) and no study was focused on evaluating if complete revascularization is able to improve the prognosis in these patients. The contemporary complete revascularization is represented by a functionally-driven revascularization that recently showed to significantly reduce myocardial infarction rate and outperformed an angio-complete revascularization. Thus, our hypothesis is that a functionally-driven complete revascularization in elderly patients with MI and multivessel disease may improve prognosis compared to the actual standard of care in these patients, namely culprit only revascularization. Being a "strategy" trial, we identified the patient-oriented composite endpoint (POCE) as primary outcome of interest (all cause death, any MI, any stroke, any revascularization).

Several pre-specified substudies have been planned. A detailed list of the substudies is available in the website of the trial (http://www.thefiretrial.com)

Condition or Disease	Intervention/Treatment	Phase
Myocardial Infarction	Other: Culprit-only revascularization Other: Complete functionally-guided revascularization	N/A

Detailed Description

BACKGROUND OF THE STUDY

Acute myocardial infarction (AMI) is the most frequent clinical presentation in older adults (≥75 years). Registry data shows that up to 65% of patients ≥75 years with AMI has multivessel disease, namely at least one lesion beyond the culprit one with diameter stenosis

50% and located in a coronary artery different from the culprit vessel. Presence of multivessel disease is a marker of worse prognosis. The rate of adverse events, such as death and MI is 3-fold higher in multivessel disease patients if compared to single vessel disease patients. During a 3-5 years follow-up, the number of adverse events related to non-culprit lesions is double than the one related to culprit lesions (data from SWEDEHEART registry and PROSPECT trial). These adverse events are even more frequent in older adults reaching a 15-30% incidence at 1 year. Several studies were focused on older adults with AMI in order to optimize their treatment. The main focus of those studies were: optimal dual antiplatelet therapy (DAPT) duration and type of stent. As for DAPT, data is in favour of a short regimen (1-6 months) as it represents the best balance between ischemic protection and reduction of bleeding events. In both LEADERS FREE and ZEUS trials, age was the main criteria for enrollment and it was considered as a marker of high risk of bleeding event. In the ongoing XIENCE 28 study, age ≥75 years is considered a sufficient criteria to prescribe 28 days of DAPT after stent implantation.

As for stent type, the recent SENIOR trial showed that biodegradable polymer second generation drug eluting stents (DES) are the gold standard in older adults receiving percutaneous coronary interventions (PCI). These stents clearly outperformed bare metal stents with a low event rate in presence of a short DAPT regimen. Thus, at the present time, we have sufficient data to consider biodegradable polymer DES and short DAPT as cornerstones of the treatment in older adults with MI. On the contrary, we have no scientific evidence regarding the best treatment strategy to apply in multivessel disease patients. It is not clear whether to prefer a culprit only strategy or if revascularization of non-culprit lesions is associated to a reduction of adverse events.

Culprit lesion treatment with PCI and stent implantation in MI setting is universally agreed as gold standard since it reduces morbidity and mortality. In the last 10 years, several studies were focused on the treatment of non-culprit lesions. PRAMI, CULPRIT, DANAMI 3 PRIMULTI, COMPARE ACUTE trial tried to assess if a systematic treatment of non-culprit lesions was associated with an improved prognosis if compared to a culprit only strategy. All these studies showed that complete revascularization clearly reduce the risk of repeated revascularizations. However, no study showed a significant impact on death or MI. When pooled in a meta-analysis, we can observe a trend in favour of MI reduction but data cannot be considered as conclusive. In 2019, COMPLETE trial results will be disclosed. In COMPLETE trial, more than 4000 patients were enrolled with consequent power to detect a difference in terms of death and MI. The limits of all the above mentioned studies are that the mean age was around 60 years and that only ST-segment elevated MI (STEMI) patients were included. No study included a relevant portion of patients ≥75 years nor included no-STEMI (NSTEMI) patients. However, a culprit lesion is identifiable in more than 90% of NSTEMI patients and the issue on their management is similar to the one of the STEMI patients. In addiction, in older adults, clinical presentation is as NSTEMI in more than 70% of the cases. Consequently, it is mandatory to generate solid data on the correct treatment strategy in these patients.

In younger adults (<65 years), in concordance with the solid scientific evidences, it is widespread a complete revascularization strategy. In older adults (≥75 years), also guidelines, in absence of clear data, suggest a case-by-case decision and suggest to consider age as one of the determinants of the final decision (Class IIa level of evidence C, ESC NSTEMI guidelines). Both European and American registry data shows clearly that the most frequently applied strategy is the culprit only one, both in STEMI and NSTEMI patients. Also in the LEADERS FREE trial, patients ≥75 years had multivessel disease in 65% of the cases, but in more than 80% of them, treatment was limited to the culprit lesion. In conclusion, the actual gold standard of treatment in older adults with MI and multivessel disease is the culprit-only strategy. The traditional concept of complete revascularization was based on angiography. Operator visually identified the lesions >50% and decided to treat or not each one of them. Contemporary data on fractional flow reserve and instantaneous free-wave ratio demonstrated that an angio-guided strategy is similar to a coin toss in terms of detection of lesions causing ischemia. This leads to unnecessary PCIs or avoided necessary PCIs in more than 50% of the cases. Studies on angio-complete revascularization probably failed to show an MI reduction because of this reason. In addition, long-term follow-up data of lesions functionally deferred shows that the rate of death and MI at 5 years is below 3%. As a consequence, functional revascularization should be considered as contemporary strategy to achieve a real complete revascularization.

Study Design

Study Type:

Interventional

Actual Enrollment :

1445 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

All comers, prospective, randomized, multicenter, open-label trial with blinded adjudicated evaluation of outcomes (PROBE).All comers, prospective, randomized, multicenter, open-label trial with blinded adjudicated evaluation of outcomes (PROBE).

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Functional Versus Culprit-only Revascularization in Elderly Patients With Myocardial Infarction and Multivessel Disease

Actual Study Start Date :

Jul 15, 2019

Anticipated Primary Completion Date :

Oct 1, 2022

Anticipated Study Completion Date :

Sep 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Other: Culprit-only revascularization All patients randomized to culprit only revascularization must not undergo percutaneous coronary intervention (PCI) any lesion except from the culprit lesion already treated at the moment of the randomization. Staged procedures are considered protocol violation.	Other: Culprit-only revascularization Implantation of drug eluting stents with biodegradable polymer with struts ≤65 μ in the culprit lesion of the MI. Each patient should receive revascularization with Supraflex stent or its newer versions
Other: Complete functionally-guided revascularization Patients who are randomized to this strategy will receive revascularization of the culprit lesion and guided by functional assessment on all non-culprit lesions. Functional evaluation is mandatory for all stenosis with diameter stenosis % between 50 and 90% at visual estimation. Revascularization must be guided by functional assessment on all vessels. The system utilized to obtain functional evaluation is left to Operator's discretion. PCI is allowed only if functional evaluation is positive according to the threshold of the chosen functional system. It is suggested to achieve functional complete revascularization within the index procedure, while it is mandatory to obtain it within the index hospitalization.	Other: Complete functionally-guided revascularization Implantation of drug eluting stents with biodegradable polymer with struts ≤65 μ in the culprit lesion of the MI and in all non culprit lesions with positive functional assessment. Each patient should receive revascularization with Supraflex stent or its newer versions

Arm

Intervention/Treatment

Other: Culprit-only revascularization

All patients randomized to culprit only revascularization must not undergo percutaneous coronary intervention (PCI) any lesion except from the culprit lesion already treated at the moment of the randomization. Staged procedures are considered protocol violation.

Other: Culprit-only revascularization

Implantation of drug eluting stents with biodegradable polymer with struts ≤65 μ in the culprit lesion of the MI. Each patient should receive revascularization with Supraflex stent or its newer versions

Other: Complete functionally-guided revascularization

Patients who are randomized to this strategy will receive revascularization of the culprit lesion and guided by functional assessment on all non-culprit lesions. Functional evaluation is mandatory for all stenosis with diameter stenosis % between 50 and 90% at visual estimation. Revascularization must be guided by functional assessment on all vessels. The system utilized to obtain functional evaluation is left to Operator's discretion. PCI is allowed only if functional evaluation is positive according to the threshold of the chosen functional system. It is suggested to achieve functional complete revascularization within the index procedure, while it is mandatory to obtain it within the index hospitalization.

Other: Complete functionally-guided revascularization

Implantation of drug eluting stents with biodegradable polymer with struts ≤65 μ in the culprit lesion of the MI and in all non culprit lesions with positive functional assessment. Each patient should receive revascularization with Supraflex stent or its newer versions

Outcome Measures

Primary Outcome Measures

Patient oriented cardiac events [1-year]
cumulative occurrence of all-cause death, any MI, any stroke, any coronary revascularization

Secondary Outcome Measures

Patient oriented cardiac events [3-year]
cumulative occurrence of all-cause death, any MI, any stroke, any coronary revascularization
Patient oriented cardiac events [5-year]
cumulative occurrence of all-cause death, any MI, any stroke, any coronary revascularization
Daily activities and quality of life [1-year]
quality of life in study groups as assessed by EQol-5D questionnaire
Physical performance [1-year]
quality of life in study groups as assessed by Short Physical Performance Battery
Residual angina [1-year]
residual angina in study groups as assessed by Seattle Angina Questionnaire
Bleeding complications [1-year]
BARC 3-5 bleedings
Cardiac death [1-year]
cumulative occurrence of cardiac death

Eligibility Criteria

Criteria

Ages Eligible for Study:

75 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients ≥75 years AND
MI (ST-segment elevation or not ST.segment elevation MI) with indication to invasive management AND
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 AND
Successful treatment of culprit lesion

Exclusion Criteria:

Planned surgical revascularization
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
Non culprit lesion located in the left main

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Maria Cecilia Hospital	Cotignola	Ravenna	Italy
2	Ospedale Maggiore	Bologna		Italy
3	Casa di Cura San Michele Maddaloni	Caserta		Italy
4	AOU Ferrara	Ferrara		Italy	44124
5	Casa di Cura Montevergine	Mercogliano		Italy
6	Ospedale Civile di Baggiovara	Modena		Italy
7	Ospedale Santa Maria delle Croci	Ravenna		Italy
8	Arcispedale Santa Maria Nuova	Reggio Emilia		Italy
9	Ospedale Infermi	Rimini		Italy
10	Ospedale Umberto I	Siracusa		Italy
11	Ospedale San Giovanni Evangelista	Tivoli		Italy
12	Ospedale di Rivoli	Torino		Italy
13	Centrum Kardiologii Inwazyjnej, Elektroterapii i Angiologii	Krosno		Poland
14	Centrum Kardiologii Inwazyjnej, Elektroterapii i Angiologii	Nowy Sącz		Poland
15	Centrum Kardiologii Inwazyjnej Elektroterapii i Angiologii	Ostrowiec Świętokrzyski		Poland
16	Centrum Kardiologii Inwazyjnej Elektroterapii i Angiologii	Oświęcim		Poland
17	Centrum Kardiologii Inwazyjnej, Elektroterapii i Angiologii	Pińczów		Poland
18	Podkarpackie Centrum Interwencji Sercowo-Naczyniowych	Sanok		Poland
19	Szpital Powiatowy im. Tytusa Chałubińskiego	Zakopane		Poland
20	Hospital General Universitario de Ciudad Real	Ciudad Real		Spain
21	Complejo Hospitalario de La Coruna	La Coruña		Spain
22	Hospital Universitario Lucus Augusti	Lugo		Spain
23	Hospital Clinico San Carlos	Madrid		Spain
24	Hospital General Universitario Gregorio Maranon	Madrid		Spain
25	Hospital Universitario La Paz	Madrid		Spain
26	Complejo Hospitalario Universitario de Santiago	Santiago De Compostela		Spain
27	Hospital Universitario La FE	Valencia		Spain
28	Hospital Clinico Universitario	Valladolid		Spain
29	Hospital Alvaro Conqueiro de Vigo	Vigo		Spain