By Jeffrey Zimmet, MD, PhD

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

Dr. Zimmet reports no financial relationships relevant to this field of study.

SYNOPSIS: This trial randomized patients with ST elevation myocardial infarction and at least one non-infarct artery with angiographically significant stenosis to either fractional flow-reserve-guided complete revascularization by percutaneous coronary intervention or to no revascularization of noninfarct arteries. The primary composite endpoint was significantly lower in the complete revascularization group, driven by a reduction in later revascularization.

SOURCE: Smits PC, Abdel-Wahab M, Neumann FJ, et al. Fractional flow reserve-guided multivessel angioplasty in myocardial infarction. N Engl J Med 2017;376:1234-1244.

Up to half of patients presenting with ST elevation myocardial infarction (STEMI) have angiographically significant stenoses in other vessels at the time of intervention. Guidelines from the American College of Cardiology, the American Heart Association, and the European Society of Cardiology recommend treatment of the infarct-related artery only. Several clinical trials over the past several years have challenged this concept. The PRAMI trial from 2013 randomized 465 patients with STEMI to infarct artery-only percutaneous coronary intervention (PCI) vs. “preventive” PCI of other angiographically significant lesions, and reported a significant benefit in terms of recurrent angina, nonfatal myocardial infarction (MI), and cardiac death. The DANAMI 3 trial, published in 2015, randomized 627 STEMI patients to either no further invasive treatment (beyond PCI of the infarct artery) or to complete fractional flow-reserve (FFR)-guided revascularization prior to discharge. This trial demonstrated a benefit in terms of major adverse cardiac events, but this was driven primarily by a reduction in the need for subsequent ischemia-driven revascularization. The CvLPRIT trial, published in 2015, enrolled 295 patients and showed a benefit in terms of the composite endpoint, but was too small to show a significant decrease in any individual components of this endpoint.

Smits et al conducted the largest trial to date looking at this question. Between mid-2011 and late 2015, 885 patients presenting with STEMI and multivessel disease were enrolled at 24 centers in Europe and Asia. Patients were randomized 1:2 to either FFR-guided complete revascularization or to treatment of the infarct-related artery only. In contrast to earlier studies, all angiographic stenoses of 50% or more were interrogated by FFR in all patients in both groups. However, intervention was performed only in the complete revascularization group, and the patient and outpatient providers were kept blinded to the FFR results (but not to the angiography results). The primary endpoint was a 12-month composite of all-cause death, any revascularization, and cerebrovascular events. Elective, clinically indicated PCI procedures performed within 45 days of the STEMI presentation were excluded (primarily lesions believed clearly to be angiographically severe at the time of the index procedure).

FFR was successfully performed in all but 18 of 885 patients. Among the complete revascularization patients, 158 of 292 (54.1%) exhibited at least one vessel with FFR < 0.80 and underwent PCI. More than 80% of these PCIs were performed during the index procedure, while the remainder were completed within three days. Among the infarct artery-only patients, 275 of 575 (47.8%) exhibited FFR-positive lesions, and 59 patients underwent staged elective revascularization within 45 days based on clinical and angiographic data; only 44 of these had positive FFRs.

At one year, 23 patients in the complete revascularization group (7.8%) and 121 patients in the infarct artery-only group (20.5%) experienced major adverse cardiac events (MACE, hazard ratio [HR], 0.35; P < 0.001). This difference was driven almost entirely by a higher incidence of revascularization in the infarct-only group. Mortality was not significantly different between groups. Although there was a trend toward a reduction in MI in the complete revascularization group, this did not meet statistical significance (HR, 0.50; 95% confidence interval, 0.22-1.13; P = 0.10). Among subsequent revascularization procedures, approximately one-third were for unstable angina.

The authors concluded that for patients presenting with STEMI and multi-vessel disease, FFR-guided complete revascularization in the acute setting resulted in a decrease in MACE, driven primarily by a reduction in subsequent revascularization procedures.

COMMENTARY

With this, the fourth and largest trial to date of the complete vs. infarct artery-only revascularization saga, do we finally have an answer? This trial demonstrates that the strategy of FFR-guided complete revascularization is feasible, and for the most part can be accomplished safely, even during the index procedure. Remarkably, the average procedure time for the complete revascularization group was only six minutes longer than in the comparator group, and the mean volume of contrast was only 10% higher. For the relatively low-risk patients enrolled in this trial (hemodynamically stable, excluding Killip 3 and 4 patients, and following successful uncomplicated intervention of the infarct-related artery) subsequent FFR-guided interventions can be undertaken with an acceptable risk profile. That is not to say that it should be done, or that it is risk free. Notably, two very serious adverse events occurred during FFR in this trial. In one, the FFR wire led to dissection of the nonculprit right coronary artery, leading to MI and in-hospital death. In the other, the FFR wire led to occlusion of the nonculprit left anterior descending artery, requiring urgent intervention. Clearly, some judgment is required to decide when evaluation of a nonculprit vessel is indicated during the initial procedure. Middle-of-the-night STEMI interventions, potentially conducted by tired operators, should not be prolonged routinely by FFR of non-culprit vessels.

The finding that the strategy of FFR-guided complete revascularization led to lower rates of MACE at one year is compelling and adds to the body of evidence supporting revascularization of non-culprit vessels identified at the time of STEMI. However, the benefit in this case mainly was driven by reduced subsequent revascularizations, and most of these were not in the setting of acute coronary syndromes. Ultimately, even larger trials with sufficient power to speak to hard clinical endpoints (nonfatal MI and cardiovascular death) will be needed to answer this question fully, and to identify the patients who are most likely to benefit from immediate complete revascularization.