By Jeffrey Zimmet, MD, PhD

Associate Professor of Medicine, University of California, San Francisco; Director, Cardiac Catheterization Laboratory, San Francisco VA Medical Center

SYNOPSIS: In this study of patients presenting with ST-elevation myocardial infarction and multivessel disease, nonculprit vessel percutaneous coronary intervention (PCI) guided by fractional flow reserve failed to show benefit vs. angiography-guided PCI in terms of clinical events at one year.

SOURCE: Puymirat E, Cayla G, Simon T, et al. Multivessel PCI guided by FFR or angiography for myocardial infarction. N Engl J Med 2021; May 16. doi: 10.1056/NEJMoa2104650. [Online ahead of print].

Back in 2009, the authors of the Fractional Flow Reserve Versus Angiography for Multivessel Evaluation (FAME) trial demonstrated that the use of fractional flow reserve (FFR) to guide coronary intervention in stable coronary disease or non-ST-elevation acute coronary syndrome results in lower rates of coronary stenting vs. angiography guidance, with a lower risk of major cardiovascular events during follow-up.1 Since that time, several research groups have demonstrated the benefits of complete revascularization of multivessel disease following ST-elevation myocardial infarction (STEMI). Some have used angiography to guide this treatment, and some have used FFR. To date, none have compared the two decision-making techniques in STEMI patients.

The Flow Evaluation to Guide Revascularization in Multivessel ST-elevation Myocardial Infarction (FLOWER-MI) trial was designed to test the hypothesis that FFR guidance would improve outcomes in treatment of STEMI patients with multivessel disease. To this end, Puymirat et al randomized 1,171 such patients presenting to 41 centers in France who had undergone successful treatment of the infarct-related artery to guidance of complete revascularization by either FFR or by angiography. Although revascularization of nonculprit vessels during the index procedure was encouraged, only about 4% of cases were actually performed this way. The remainder were managed as staged procedures before hospital discharge, on average two to three days after the initial presentation. In the FFR-guidance group, all lesions judged to be at least 50% severity were to be evaluated by FFR, with percutaneous coronary intervention (PCI) guided by FFR values of 0.80 or smaller, as per current guidelines. Overall, FFR was attempted in more than 95% of patients in the FFR group and was successful in the majority. PCI was performed in 388 of 586 patients in the FFR-guided group and in 560 of 577 patients in the angiography-guided group. This resulted in a lower number of stents used per patient in the FFR group. Procedure times were slightly higher in the FFR group compared with angiography (35 minutes vs. 30 minutes).

At one year, the primary outcome of all-cause death, MI, and unplanned urgent revascularization occurred in 5.5% of patients in the FFR group and in 4.2% of patients in the angiography group, which did not represent a significant difference (HR, 1.32; 95% CI, 0.78-2.23; P = 0.31). Rates of nonfatal MI (18 vs. 10) and any revascularization (38 vs. 26) were numerically greater in the FFR group, but these also did not reach statistical significance. The authors concluded in patients with STEMI and multivessel disease undergoing complete revascularization, FFR guidance did not show a benefit over angiography guidance in terms of the risk of death, MI, and repeat revascularization at one year.


The overall message of the FAME trial, and of subsequent trials, has been remarkably consistent over time. Using FFR to guide PCI outside the realm of STEMI predictably leads to lower rates of coronary stenting and better cardiovascular outcomes vs. angiography alone to guide treatment decisions. The improved outcomes presumably result from selecting lesions that are more physiologically significant for treatment, reserving PCI for those who will benefit and preventing the complications of stenting in those who will not. Part of the lesson here is PCI in patients with stable angina clearly differs from treatment of nonculprit lesions after STEMI. Generally, PCI in stable disease has not been associated with improvements in hard cardiovascular endpoints over periods of a year or less. In contrast, multiple trials have demonstrated benefit to a complete revascularization strategy after presentation with STEMI. The COMPLETE trial demonstrated improvements in rates of cardiovascular death and MI among patients with complete revascularization vs. culprit lesion-only PCI.2 This brings up the concept that nonculprit lesions in STEMI patients are less inherently “stable,” and may benefit from stenting. The authors of the COMPLETE trial reported that event curves started to visually diverge after six months, with higher rates of the primary outcome in the FFR group. It is likely some lesions left untreated in the FFR group progressed during follow-up, leading to the observed increase in event rates. The result is that less PCI is not better in the context of the post-STEMI patient. It will be interesting to see the longer-term results from this trial, once available.

Most nonculprit revascularization procedures in the FLOWER-MI trial were performed as staged procedures, several days after the STEMI presentation. The result here prevents the potential problems with interpretation of FFR in the context of ongoing STEMI, with potential confounding by arterial spasm and microvascular obstruction. However, the authors still did not demonstrate the benefits of FFR seen in more stable coronary disease. While we should be careful about applying the results to revascularization performed during the index procedure, the use of FFR early after the acute phase of a STEMI to accomplish complete revascularization would appear to be optional. 


  1. Tonino PA, De Bruyne B, Pijls NH, et al. Fractional flow reserve versus angiography for guiding percutaneous coronary intervention. N Engl J Med 2009;360:213-224.
  2. Mehta SR, Wood DA, Storey RF, et al. Complete revascularization with multivessel PCI for myocardial infarction. N Engl J Med 2019;381:1411-1421.