Timing of FFR-guided PCI for Non-IRA in NSTEMI and MVD (OPTION-NSTEMI)

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.

• Rate of contrast-induced nephropathy [Time frame: Up to 12 months]
• Cumulative incidence rate of all unplanned revascularization [Time frame: Index admission, 1 month, 6 months, 12 months, 24 months, 36 months, 48 months, 60 months]
• Cumulative incidence rate of target-lesion revascularization [Time frame: Index admission, 1 month, 6 months, 12 months, 24 months, 36 months, 48 months, 60 months]
• Cumulative incidence rate of target-vessel revascularization [Time frame: Index admission, 1 month, 6 months, 12 months, 24 months, 36 months, 48 months, 60 months]
• Cumulative incidence rate of non-target vessel revascularization [Time frame: Index admission, 1 month, 6 months, 12 months, 24 months, 36 months, 48 months, 60 months]
• Cumulative incidence rate of all-cause death [Time frame: Index admission, 1 month, 6 months, 12 months, 24 months, 36 months, 48 months, 60 months]
• Cumulative incidence rate of cardiac death [Time frame: Index admission, 1 month, 6 months, 12 months, 24 months, 36 months, 48 months, 60 months]
• Cumulative incidence rate of non-cardiac death [Time frame: Index admission, 1 month, 6 months, 12 months, 24 months, 36 months, 48 months, 60 months]
• Cumulative incidence rate of non-fatal myocardial infarction [Time frame: Index admission, 1 month, 6 months, 12 months, 24 months, 36 months, 48 months, 60 months]
• Cumulative incidence rate of hospitalization for unstable angina [Time frame: Index admission, 1 month, 6 months, 12 months, 24 months, 36 months, 48 months, 60 months]
• Cumulative incidence rate of hospitalization for heart failure [Time frame: Index admission, 1 month, 6 months, 12 months, 24 months, 36 months, 48 months, 60 months]
• Cumulative incidence rate of definite or probable stent thrombosis [Time frame: Index admission, 1 month, 6 months, 12 months, 24 months, 36 months, 48 months, 60 months]