New Insights From the FRAME-AMI Trial: Supporting Physiology-Guided Complete Revascularization in Acute Myocardial Infarction

The concept of complete revascularization (CR) in patients with multi-vessel disease has been debated since the inception of primary coronary intervention, especially in those presenting with ST-elevation myocardial infarction (STEMI). Key questions include whether to perform CR or not, the optimal timing of CR, the mode of revascularization, and how to evaluate the severity of non-infarct-related artery (non-IRA) stenosis. Contemporary guidelines now recommend CR in patients with acute coronary syndrome based on major clinical trials in this field.¹⁾,²⁾ While CR is strongly recommended in patients with STEMI (class of recommendation I, level of evidence A), the strength of recommendation and evidence is lower for non-ST-elevation acute coronary syndrome (NSTE-ACS), especially regarding the timing and method (physiology vs. angiography) of non-culprit lesion (NCLs) intervention.

The role of physiological assessment of NCLs is still controversial. Currently, physiology-guided strategies are considered as a class 2b recommendation in only in NSTE-ACS.¹⁾,²⁾ The Fractional Flow Reserve (FFR) vs. Angiography-Guided Strategy for Management of Non-Infarction Related Artery Stenosis in Patients With Acute Myocardial Infarction (FRAME-AMI) trial, conducted in Korea, enrolled 562 patients with acute myocardial infarction and multivessel coronary artery disease. The trial showed that a strategy of selective percutaneous coronary intervention (PCI) using FFR-guided decision-making was superior in reducing the risk of death, MI, or repeat revascularization to a strategy of routine PCI based on angiographic diameter stenosis for treatment of non-IRA lesions.³⁾ Another major piece of evidence in this area is the Flow Evaluation to Guide Revascularization in Multivessel ST-Elevation Myocardial Infarction (FLOWER-MI) trial, which was published several years earlier. A total of 1,171 patients with STEMI were randomized to show no substantial benefit of an FFR-guided strategy.⁴⁾ Thus, there have been interpretations to explain the differing results between the 2 trials.⁵⁾

One plausible explanation is the difference in the inclusion criteria: the FLOWER-MI trial exclusively enrolled STEMI, while the FRAME-AMI enrolled both STEMI and non-ST-elevation myocardial infarction (NSTEMI) (47.2% of STEMI and 52.8% of NSTEMI). Subgroup analyses of the FRAME-AMI trial showed that the benefit of the FFR-guided strategy was numerically greater in the NSTEMI subgroup than in the STEMI subgroup. Additional differences include the timing of non-culprit PCI and the follow-up duration. A substudy from the FRAME-AMI trial indicates that FFR-guided PCI poses a lower risk of primary endpoint than angiography-guided PCI regardless of the severity of non-IRA stenosis without significant interaction.

In this issue of the journal, Jeon et al.⁶⁾ present a prespecified subgroup analysis of the FRAME-AMI trial, exploring whether the location of NCLs influences treatment outcomes. They analyzed 562 patients—309 with lesions in the left anterior descending artery (LAD) and 253 with lesions elsewhere. The primary endpoint occurred in 9.4% of the non-culprit LAD group and 11.5% of the non-culprit non-LAD group. Notably, the benefit of FFR-guided vs. angiography-guided non-culprit PCI did not show significant interaction according to the location of the NCLs (interaction p=0.667).

One interesting finding of this manuscript is the discrepancy between the anatomical and functional severity. Diameter stenosis measured by quantitative coronary analysis was similar in the FFR guidance group in the non-culprit LAD and non-LAD subgroups (70.0% and 73.0%, respectively). However, the mean FFR value 0.77 and 0.83 and the proportion of hemodynamic significance (FFR ≤0.8 or diameter stenosis >90%) was significantly higher in the LAD subgroup (approximately 74% and 58%, respectively). This highlights the importance of physiological evaluation, as visual assessment alone can sometimes underestimate or overestimate lesion severity, especially depending on lesion location.⁷⁾

Future studies, such as the ongoing larger-scale Physiology-guided vs. Angiography-guided Non-culprit Lesion Complete Revascularization for Acute MI & Multivessel Disease (COMPLETE-2) trial, aim to compare the 2 strategies with an estimated enrollment of 5,100 patients with STEMI and NSTEMI with a minimum follow-up duration of 2 years.⁸⁾ In addition, the FRAME-AMI2 is enrolling patients to compare intravascular ultrasound-guided vs. FFR-guided treatment decision for non-infarct related artery stenosis.⁹⁾ The results of these investigations are eagerly awaited and will further inform best practices in the management of AMI with multivessel disease.