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: In this largest trial to date, patients who were randomized to complete revascularization by percutaneous coronary intervention (PCI) following successful intervention at the time of ST-elevation myocardial infarction (STEMI) had a lower risk of cardiovascular death, myocardial infarction, and ischemia-driven revascularization vs. patients who underwent culprit lesion-only PCI.
SOURCE: Mehta SR, Wood DA, Storey RF, et al. Complete revascularization with multivessel PCI for myocardial infarction. N Engl J Med 2019; Sep 1. doi: 10.1056/NEJMoa1907775. [Epub ahead of print].
Patients presenting with STEMI often exhibit significant disease of the noninfarct-related vessels. For years, one question was whether PCI of nonculprit vessels could or should be undertaken at the time of the initial STEMI procedure. For example, in the Preventive Angioplasty in Myocardial Infarction (PRAMI) trial, the authors focused attention on the value of PCI in noninfarct coronary vessels. However, the trial was relatively small in size and required additional angioplasty be performed at the time of primary PCI.1 By far, the more common paradigm is that only the infarct-related vessel is treated at the time of STEMI presentation. Cardiologists are left to decide whether to recommend further elective PCI to achieve complete revascularization. Enter the COMPLETE study, a trial designed to answer this question once and for all. Mehta et al enrolled 4,041 patients from 140 unique centers in 31 countries, randomizing 1:1 to either complete revascularization or culprit lesion-only PCI. Patients were randomized within 72 hours of successful culprit lesion PCI. Subjects assigned to the complete revascularization group were to undergo a staged PCI procedure either during the index hospitalization or after discharge, but no more than 45 days after group assignment. All eligible lesions (those judged to be at least 70% angiographically or 50-69% with a positive fractional flow reserve [FFR] measurement) were to be intervened on regardless of subsequent symptoms or noninvasive testing. Conversely, patients assigned to the culprit-only group received medical therapy alone. Within the first 45 days, 96 patients in the culprit-only group crossed over to complete revascularization, while 78 patients in the complete revascularization group crossed over to culprit lesion-only PCI.
At a median of three years follow-up, patients assigned to the complete revascularization group demonstrated a lower risk of cardiac death or new myocardial infarction (MI; 7.8% vs. 10.5%; hazard ratio [HR], 0.74; 95% confidence interval, 0.6-0.91; P = 0.004). This difference was driven by a reduced risk for new MI (5.4% vs. 7.9%). Death from cardiovascular causes was not significantly different (approximately 3% in each group). Among other secondary outcomes, ischemia-driven revascularization (1.4% vs. 7.9%; HR, 0.18; 95% CI, 0.12-0.26) and unstable angina (3.5% vs. 6.4%; HR, 0.53; 95% CI, 0.40-0.71) also were significantly lower in the complete revascularization group.
In this study of patients with STEMI and multivessel disease, the authors concluded that complete revascularization by staged PCI was superior to culprit lesion-only PCI, with outcomes driven by reductions in MI and ischemia-driven revascularization.
Multivessel disease in patients presenting with STEMI is extremely common, affecting up to an estimated half of all subjects. To date, four smaller trials have addressed the question of pursuing nonculprit lesions, primarily at the time of the initial procedure. In real-world practice, primary PCI can occur at any time and can be complicated. Although the prior prohibition against nonculprit PCI at the time of STEMI has been removed, patients in most cases are best served by addressing the culprit lesion only at the index procedure, taking the time to achieve an optimal result. Therefore, Mehta et al sought to address this everyday question in clinical cardiology: For the patient who has undergone successful primary PCI, is it reasonable and advantageous to recommend further PCI, even in the absence of further symptoms or tests confirming ischemia?
The results are quite compelling. In addition to reducing the incidence of repeat revascularization (in relative terms, a “soft” outcome), complete revascularization by PCI in this trial also led to a significant decline in new MI. The fact that no decrease was seen in the low rate of cardiovascular or overall mortality is not surprising and should not reduce our enthusiasm for the overall outcome.
Some people may criticize the trialists for not requiring FFR assessment of lesion severity before committing to revascularization. The fact that lesions could qualify for intervention with a visual estimate of 70% suggests that some lesions might not have required intervention had they been subjected to functional assessment. Available trial evidence suggests that the use of FFR in the general case decreases the use of PCI while improving clinical outcomes compared to the use of visual estimates alone. Therefore, the fact that FFR was not mandated in this trial for lesions estimated to be 70% or greater would, if anything, dilute the positive result of the study. In no way should this omission dissuade cardiologists from using functional studies such as FFR in suitable patients and lesions.
It is relatively uncommon that the results of a single trial change practice guidelines. However, in this case, I suspect that we will see increasing referrals for complete percutaneous revascularization after STEMI, at least in patients with suitable anatomy.
- Wald DS, Morris JK, Wald NJ, et al. Randomized trial of preventive angioplasty in myocardial infarction. N Engl J Med 2013;369:1115-1123.