By Jeffrey Zimmet, MD, PhD
Associate Professor of Medicine, University of California, San Francisco; Director, Cardiac Catheterization Laboratory, San Francisco VA Medical Center
SYNOPSIS: Among patients at least age 75 years presenting with acute myocardial infarction and multivessel coronary disease, physiology-guided complete revascularization led to a lower risk of major adverse cardiovascular events at one year vs. culprit lesion-only percutaneous coronary intervention.
SOURCE: Biscaglia S, et al. Complete or culprit-only PCI in older patients with myocardial infarction. N Engl J Med 2023; Aug 26. doi: 10.1056/NEJMoa2300468. [Online ahead of print].
Percutaneous coronary intervention (PCI) has shown efficacy when treating culprit lesions in acute myocardial infarction (MI). In ST-elevation MI (STEMI) specifically, multiple randomized trials have shown significant reductions in hard endpoints through planned interventional treatment of significant nonculprit lesions as well.
The largest and most influential of these was the COMPLETE trial.1 During that study, researchers randomized 4,041 patients with STEMI and at least one significant nonculprit lesion to complete revascularization or to culprit-only PCI. Staged complete revascularization by angiographically guided PCI led to improvements in the composite endpoint of cardiovascular death and new MI, as well as in quality of life. Several major questions remain unanswered when it comes to whether to submit patients to subsequent PCI procedures after initial management of the acute infarct. The first concerns managing patients with non-ST elevation acute coronary syndrome, and whether these patients would respond similarly as STEMI patients. Compared with STEMI, non-NSTEMI (NSTEMI) patients tend to be older, present with a greater degree of medical comorbidities, and record higher intermediate- and long-term mortality rates. The mean age of STEMI patients enrolled in COMPLETE was only 62 years. There are a lack of trial data regarding complete revascularization specifically in older populations.
The FIRE trial was designed to fill some of these gaps. In this multinational study conducted at 34 sites in Italy, Spain, and Poland, patients were screened for enrollment if they were at least age 75 years, had been admitted with either STEMI or NSTEMI where the culprit lesion had been successfully treated by PCI, and had at least one nonculprit vessel with visually estimated stenosis of at least 50%.
Over the course of two years, researchers randomly assigned 1,445 patients to receive either physiology-guided complete revascularization (n = 720) or culprit-only revascularization (n = 725). The median age for patients was 80 years, 35% had been admitted with STEMI, and 65% had been admitted with NSTEMI). Among patients assigned to the complete revascularization arm, so-called physiologic guidance could be performed either by traditional wire-based methods (fractional flow reserve, instantaneous wave-free ratio) or by angiography-based measurements (quantitative flow ratio). After performing a qualifying physiologic test, 361 patients actually underwent PCI.
At the one-year follow-up, patients in the complete revascularization group had a lower incidence of the primary composite endpoint of death, MI, stroke, or any revascularization (15.7% vs. 21%; HR, 0.73; 95% CI, 0.57-0.93; P = 0.01). Importantly, all-cause mortality was lower in the complete revascularization group (9.2% vs. 12.8%; HR, 0.70; 95% CI, 0.51-0.96), as was the secondary composite endpoint of cardiovascular death or MI. Safety endpoints, weighted toward procedure-related complications (including contrast nephropathy, bleeding, and stroke), were not significantly different between groups. The authors concluded that among older patients with MI and multivessel disease, a physiology-guided complete revascularization approach led to a reduction in important cardiovascular outcomes at one year compared to a culprit-only approach.
COMMENTARY
The FIRE study provides another reminder that post-MI patients are fundamentally different from those with stable atherosclerotic disease and must be viewed through a different lens when it comes to consideration of percutaneous revascularization. The results of this trial muddy the waters somewhat in providing guidance by mixing together all acute MI patients — with the caveat that it required the culprit lesion to be clearly identifiable (as is not always the case with NSTEMI). The fact nearly two-thirds of study subjects were enrolled after an NSTEMI event strongly suggests an advantage to complete revascularization in this largest subset of MI patients.
Although FIRE was relatively modest in size, event rates in this significantly older population were high — significantly higher than in comparable trials that enrolled younger patients.1 This allowed for the detection of a significant result within the one-year follow-up time. Note that safety endpoints (bleeding, contrast nephropathy, and stroke) also were high, affecting a little more than 20% of the patients in each group.
This study does not answer the question about whether angiography-guided or physiology-guided strategies are best. At least one large study (FLOWER-MI) failed to demonstrate a benefit to physiologic (vs. angiographic) guidance for nonculprit revascularization in the STEMI population.2 In contrast to the case with stable atherosclerotic disease, lesions in post-MI patients that miss established physiology cutoffs still may contain features consistent with unstable plaques and may confer a higher risk of recurrent events.
The use of physiology in FIRE meant many of the qualifying nonculprit lesions that were included based on visual estimates were deemed not significant. Thus, only half of patients assigned to the complete revascularization group actually received PCI of a nonculprit lesion. Part of this resulted from the relatively lax requirement that these secondary lesions have a minimum stenosis of only 50%.
What would the results have shown had the inclusion required a positive physiologic test first, or a greater degree of angiographic stenosis (70% or 80%)? Presumably, the effect of complete revascularization here is diluted by the fact that only half of patients actually required, and then received, additional PCI. When faced with patients in this category, we should consider the magnitude of possible benefit and balance this with anticipated PCI complexity and the possible harms of additional revascularization. Markers of PCI difficulty, including extreme calcification or tortuosity, bifurcation lesions, or chronic total occlusions, certainly may temper the clinician’s enthusiasm about submitting older patients to additional procedures. For now, FIRE represents the best available evidence. When achievable with average risk, we should consider complete revascularization to be a concrete goal in most post-MI patients.
REFERENCES
1. Mehta SR, Wood DA, Storey RF, et al. Complete revascularization with multivessel PCI for myocardial infarction. N Engl J Med 2019;381:1411-1421.
2. Puymirat E, Cayla G, Simon T, et al. Multivessel PCI guided by FFR or angiography for myocardial infarction. N Engl J Med 2021;385:297-308.
Among patients at least age 75 years presenting with acute myocardial infarction and multivessel coronary disease, physiology-guided complete revascularization led to a lower risk of major adverse cardiovascular events at one year vs. culprit lesion-only percutaneous coronary intervention.
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