Clinical trial NCT04968808: Timing of FFR-guided PCI for Non-IRA in NSTEMI and MVD (OPTION-NSTEMI)
Official title: OPtimal TIming of Fractional Flow Reserve-Guided Complete RevascularizatiON in Non-ST-Segment Elevation Myocardial Infarction (OPTION-NSTEMI)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Myocardial Infarction, Acute
Multi-Vessel Coronary Artery Stenosis
Multi Vessel Coronary Artery Disease
Keywords: Non-ST-Segment Elevation Myocardial Infarction
Multi-Vessel Coronary Artery Disease
Multi-Vessel Coronary Artery Stenosis
Culprit-Only
Multi-Vessel Percutaneous Coronary Intervention
Percutaneous Coronary Intervention
Complete Revascularization
Timing
Staged Percutaneous Coronary Intervention
Fractional Flow Reserve
Lead sponsor: Chonnam National University Hospital
Sponsor class: OTHER
First posted: 2021-07-20
Enrollment: 1014
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Many patients with non-ST-segment elevation myocardial infarction (NSTEMI) have multivessel coronary artery disease (MVD), which is associated with poor clinical outcomes. However, there have been few studies regarding revascularization strategy in patients with NSTEMI and MVD. Therefore, we planned to perform prospective, open-label, randomized trial to evaluate the efficacy and safety of immediate complete revascularization (percutaneous coronary intervention \[PCI\] for both infarct-related artery \[IRA\] and non-IRA during index PCI) compared to staged PCI strategy of non-IRA (PCI for IRA followed by non-IRA PCI after several days). PCI procedure at non-IRA with diameter stenosis between 50 and 69% should be conducted with the aid of fractional flow reserve (FFR), and non-IRA with diameter stenosis ≥ 70% will be revascularized without FFR.

Detailed description: Many patients with non-ST-segment elevation myocardial infarction (NSTEMI) have multivessel coronary artery disease (MVD), which is associated with poor clinical outcomes. In cases of hemodynamically stable ST-segment elevation myocardial infarction (STEMI) and MVD, many studies demonstrated the superiority of complete revascularization (CR) by both one-stage and multistage procedures compared to culprit-only revascularization (COR). The 2017 European Society of Cardiology (ESC) guidelines for STEMI recommend routine revascularization for non infarct-related artery (IRA) lesions before hospital discharge in patients without cardiogenic shock.

However, there have been few studies regarding revascularization strategy in patients with NSTEMI and MVD. Only one randomized controlled trial, the SMILE trial (J Am Coll Cardiol 2016;67:264-72), compared one-stage and multi-stage multivessel revascularization (MVR) in these patients. Although the results of most studies analyzing interventional strategies in patients with NSTEMI and MVD showed superior results of MVR compared to COR, they did not provide information about staged revascularization. One-stage MVR was associated with better clinical outcomes compared to multi-stage MVR in the SMILE trial, while one-stage and multi-stage MVR had similar incidences of adverse outcomes in large registry data. Although the 2018 ESC/European Association for Cardio-Thoracic Surgery (EACTS) guidelines for myocardial revascularization recommend complete one-stage revascularization in NSTEMI and MVD, it emphasizes individualization based on clinical status and comorbidities, as well as disease severity. In 2020 ESC guidelines for non-ST-segment elevation acute coronary syndrome, this strategy is maintained. CR during index percutaneous coronary intervention (PCI) is recommended in NSTEMI patients with MVD (class IIb, level B).

Whether to revascularize non-IRA using angiography or fractional flow reserve (FFR) is also problematic. FFR is a useful tool for assessing hemodynamic significance of non-IRA during both acute and subacute stage, and FFR-guided PCI for non-IRA lesion is recommended during index PCI (class IIb, level B). In the SMILE trial, a 25.8% of study patients received FFR-guided PCI for non-IRA. Although FFR is a well-known tool to evaluate significant ischemia of moderate stenosis, the most studies regarding FFR enrolled patients without acute myocardial infarction (AMI).

However, the recommendations in current guidelines, which recommends CR during index PCI, is not sufficiently powered to assess differences in clinical outcomes between interventional strategy. There are also few studies regarding this issue, and discrepancy in clinical outcomes between randomized trial and observational studies. Furthermore, FFR-guided PCI for non-IRA is not mandatory in these studies.

Therefore, we planned to perform prospective, open-label, randomized trial to evaluate the efficacy and safety of immediate complete revascularization (PCI for both IRA and non-IRA during index PCI) compared to staged PCI strategy of non-IRA (PCI for IRA followed by non-IRA PCI after several days). PCI procedure at non-IRA with diameter stenosis between 50 and 69% should be conducted with the aid of FFR, and non-IRA with diameter stenosis ≥ 70% will be revascularized without FFR.

Eligibility criteria: Inclusion Criteria:

1. Age ≥ 19 years old
2. Non-ST-segment elevation myocardial infarction

   * Angina pectoris or equivalent ischemic chest discomfort with at least 1 of 3 features and,

     * occurs at rest, usually lasting \> 10 minutes
     * severe and new onset (within the prior 4-6 weeks)
     * crescendo pattern
   * Elevated cardiac biomarkers and,

     * ≥ 99% value of high-sensitivity cardiac troponin
   * No ST-segment elevation ≥ 0.1 mV in ≥ 2 contiguous leads or newly developed left bundle branch block on 12-lead electrocardiogram
3. PCI within 72 hours after symptom development
4. Multivessel disease: Non-IRA with at least 2.5 mm diameter and 50% diameter stenosis by visual estimation
5. Patient's or protector's agreement about study design and the risk of PCI

Exclusion Criteria:

1. Cardiogenic shock at initial presentation or after treatment of IRA
2. TIMI flow at non-IRA ≤ 2
3. Severe procedural complications (e.g. persistent no-reflow phenomenon, coronary artery perforation) which restricts study enrollment by operators' decision
4. Non-IRA lesion not suitable for PCI treatment by operators' decision
5. Chronic total occlusion at non-IRA
6. History of anaphylaxis to contrast agent
7. Pregnancy and lactation
8. Life expectancy \< 1-year
9. Severe valvular disease
10. History of CABG, or planned CABG
11. Fibrinolysis before admission

Primary outcomes:
measure: Cumulative incidence rate of all-cause death, non-fatal myocardial infarction, or all unplanned revascularization
timeFrame: Up to 12 months
Secondary outcomes:
measure: Rate of contrast-induced nephropathy
timeFrame: Up to 12 months
measure: Cumulative incidence rate of all unplanned revascularization
timeFrame: Up to 12 months
measure: Cumulative incidence rate of target-lesion revascularization
timeFrame: Up to 12 months
measure: Cumulative incidence rate of target-vessel revascularization
timeFrame: Up to 12 months
measure: Cumulative incidence rate of non-target vessel revascularization
timeFrame: Up to 12 months
measure: Cumulative incidence rate of all-cause death
timeFrame: Up to 12 months
measure: Cumulative incidence rate of cardiac death
timeFrame: Up to 12 months
measure: Cumulative incidence rate of non-cardiac death
timeFrame: Up to 12 months
measure: Cumulative incidence rate of non-fatal myocardial infarction
timeFrame: Up to 12 months
measure: Cumulative incidence rate of hospitalization for unstable angina
timeFrame: Up to 12 months
measure: Cumulative incidence rate of hospitalization for heart failure
timeFrame: Up to 12 months
measure: Cumulative incidence rate of definite or probable stent thrombosis
timeFrame: Up to 12 months
measure: Cumulative incidence rate of ischemic and hemorrhagic stroke
timeFrame: Up to 12 months
measure: Cumulative incidence rate of major bleeding (BARC [Bleeding Academic Research Consortium] definitions type 3 or 5)
timeFrame: Up to 12 months
Other outcomes:
Locations:
city: Gwangju
country: Korea, Republic of
facility: Chonnam National University Hospital
Study officials:
affiliation: Chonnam National University Hospital
name: Min Chul Kim, MD
role: PRINCIPAL_INVESTIGATOR
References: