Weekly Journal Scan: Complete revascularization in acute myocardial infarction improves major cardiovascular outcomes.

This comment refers to ‘Complete versus culprit lesion-only revascularisation for acute myocardial infarction (Complete Revascularisation Trialists’ Collaboration): an individual patient data meta-analysis of randomised trials’ which was published in the The Lancet, https://doi.org/10.1016/S0140-6736(25)02170-1. This individual patient data (IPD) meta-analysis from the Complete Revascularization Trialists’ Collaboration aimed to evaluate whether a strategy of complete revascularization, compared with culprit lesion-only percutaneous coronary intervention (PCI), improves major cardiovascular (CV) outcomes in patients with acute myocardial infarction (AMI).1 Studies were eligible if they met the following criteria: (i) randomized controlled trials (RCTs) enrolling at least 250 patients, (ii) comparison of a complete revascularization strategy vs a culprit lesion-only PCI strategy, and (iii) enrolment of patients presenting with ST-segment elevation MI (STEMI) or non-STEMI (NSTEMI). Complete revascularization was achieved through an angiography-guided or physiology-guided PCI of all suitable non-culprit lesions, in addition to PCI of the culprit lesion. Trials enrolling patients with cardiogenic shock or stable coronary artery disease (CAD) were excluded. The two coprimary endpoints were the composite of CV death or new MI and CV death alone. They were analysed in the intention-to-treat population and tested hierarchically, with CV death alone tested only in case of a statistically significant reduction in the composite endpoint with a complete revascularization strategy, at a prespecified alpha level of .04. Secondary endpoints were all-cause death, non-CV death, and new MI. The median follow-up duration was 36 months [interquartile range (IQR), 31–48]. A total of six RCTs enrolling 8836 patients (median age, 66 years; 24% female; 20% diabetic) were included, of whom 4259 patients were randomized to complete revascularization and 4577 to culprit lesion-only PCI strategy. ST-segment elevation myocardial infarction was the most frequent diagnosis (88%), and most patients (74%) had only one residual non-culprit vessel. Complete revascularization was achieved using a physiology-guided approach in four trials and an angiography-guided approach in two trials. Regarding revascularization timing, one trial recommended performing PCI of non-culprit lesions during the index procedure, three trials during a staged procedure, and two trials permitted either strategy. The first coprimary endpoint of CV death or new MI was significantly less frequent in the complete revascularization group than in the culprit-only PCI group [9.0% vs 11.5%; hazard ratio (HR), .76; 95% confidence interval (CI), .67–.87; P < .0001]. The second coprimary endpoint of CV death also occurred less frequently in the complete revascularization group than in the culprit-only PCI group (3.6% vs 4.6%; HR, .76; 95% CI, .62–.93; P = .009). As compared with culprit lesion-only PCI, complete revascularization was associated with lower rates of all-cause death (7.2% vs 8.1%; HR, .85; 95% CI, .73–.99) and new MI (6.0% vs 7.8%; HR, .76; 95% CI, .65–.90). The rate of non-CV death was similar in the two groups (3.6% vs 3.5%; HR, .98; 95% CI, .78–1.22). The results were consistent in all prespecified subgroups, including age, sex, diabetes status, type of MI, non-culprit lesion stenosis severity, and number of residual non-culprit vessels. Despite substantial progress in myocardial revascularization strategies and contemporary pharmacotherapy, patients with AMI continue to face substantial short- and long-term mortality.2 Approximately 50% of these patients have multivessel disease, which is associated with worse clinical outcomes,2 reflecting the complex pathophysiology of vulnerable plaques,3 the possible presence of multifocal plaque disruption,4 and the impact of widespread coronary inflammation in the setting of AMI.5 The PRAMI (Preventive Angioplasty in Acute Myocardial Infarction) trial was the first RCTs to evaluate the impact of complete revascularization in patients with STEMI.6 The trial was stopped prematurely after enrolment of 465 patients due to evidence of a significantly reduced risk of the composite of cardiac death, non-fatal AMI, or refractory angina with complete revascularization compared with culprit lesion-only PCI. Yet, patients with NSTEMI were excluded, and refractory angina was part of the composite primary endpoint in the context of an unblinded trial. Subsequent RCT trials showed heterogeneous results, in particular with respect to the survival benefit of complete revascularization.7–12 While the evidence supporting a complete revascularization approach is solid for patients with STEMI, less robust data are available for patients with NSTEMI and for those with haemodynamic instability or cardiogenic shock. Current European Society of Cardiology (ESC) guidelines for the management of acute coronary syndromes (ACSs) recommend a complete revascularization strategy with a Class I (Level of Evidence A) for patients with STEMI and with a Class IIa (Level of Evidence C) for those with NSTEMI.13 This IPD meta-analysis from the Complete Revascularization Trialists’ Collaboration provided the largest and most comprehensive evidence on the effects of a complete revascularization strategy compared with a culprit lesion-only PCI strategy on major CV outcomes.1 With more than 900 CV deaths or new MIs, and more than 350 CV deaths over 3 years of follow-up, it was able to show that a strategy of complete revascularization reduces the composite of CV death or new MI by approximately one-quarter, and CV death alone by a similar relative magnitude, overcoming the limited statistical power of single prior RCTs (including the large COMPLETE)10 in detecting moderate reductions in major CV outcomes. Of note, the observed benefit on the composite primary endpoint was driven by a similar relative risk reduction in both of its individual components. In absolute terms, ∼60% of the reduction in the composite endpoint was attributable to fewer new MI, while the remaining 40% was explained by a reduction in CV death. This benefit was achieved in the presence of guideline-directed medical therapy, with high proportion of patients discharged on dual antiplatelet therapy (98%), statins (97%), β-blockers (86%), and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (80%). Kaplan–Meier curves of both coprimary endpoints demonstrated a progressively widening separation, indicating that the benefits of complete revascularization may be sustained and grow over time. Moreover, as the included RCTs were open label, some patients in the culprit lesion-only PCI arm may have received subsequent non-culprit lesion revascularization during follow-up. This cross-over would be expected to dilute between-group differences, implying that the true effect size of complete revascularization might be underestimated. The large sample size of this meta-analysis allowed for a more reliable assessment of the effects of complete revascularization across key subgroups. Of note, over 2500 patients aged 75 or more were included, a subgroup generally underrepresented in RCTs. The meta-analysis showed consistent benefit across the full age range, confirming the findings of the FIRE (Functional Assessment in Elderly MI Patients with Multivessel Disease)11 demonstrating the benefit of complete revascularization in older patients with AMI. However, despite the large sample size, the majority of patients (>85%) had STEMI, with relatively few NSTEMI cases (∼1000), limiting generalizability of the results to a broader ACS population where evidence remains less clear. In fact, in NSTEMI, identifying the culprit and non-culprit lesions can be more challenging than in STEMI due to the frequent presence of diffuse atherosclerosis, multivessel plaque instability, and subtler angiographic features, which make decision-making for complete revascularization more complex, and may influence both procedural strategy and clinical outcomes.13 The results of ongoing RCTs, such as the COMPLETE NSTEMI (NCT05786131), will provide further insights into this open issue. Of note, all major RCTs of complete revascularization in AMI patients were included in the meta-analysis,7–12 with the exception of the PRAMI trial.6 However, since PRAMI was a relatively small trial, the unavailability of its IPD had no significant impact, and a sensitivity analysis incorporating its tabular data showed consistent results. Another limitation of the study is the lack of information on race and ethnicity, which hinders the evaluation of treatment efficacy across different demographic groups. Several areas of uncertainty remain, including the optimal timing for complete revascularization (immediate vs staged) and the best strategy to guide treatment of intermediate stenoses (angiography vs physiology). Of note, the functional significance of a non-culprit lesion may be underestimated in the acute phase of MI, partly as a result of increased microvascular resistance and a reduced hyperaemic response to adenosine during physiological assessment.13 On the other hand, exclusive reliance on angiographic evaluation can also be misleading, as diffuse coronary vasoconstriction commonly occurs during the acute phase of MI, which might affect stenosis assessment. Although the use of functional testing to guide treatment of non-culprit lesions may appear counterintuitive when predicting CV death or new MI (events typically caused by acute plaque rupture and related to plaque vulnerability), there is evidence suggesting a link between physiological significance and plaque instability.3 Another interesting question to address in future analyses is whether the benefits of complete revascularization persist over longer term and whether this strategy is cost-effective. In conclusion, this IPD meta-analysis adds an important piece to the puzzle of coronary revascularization in patients with AMI, demonstrating that a complete revascularization strategy has a beneficial impact on major CV outcomes, including CV mortality. Further evidence is needed to elucidate the optimal timing and guidance strategy for complete revascularization and to establish its clinical relevance more definitively in patients with NSTEMI. R.V. is a consultant for Abbott Vascular and Medtronic; received lecturing fees from Abbott Vascular, Abiomed, Amgen, Boston Scientific, Daiichi Sankyo, Edwards Lifesciences, Johnson & Johnson, Medtronic, Novartis, Novo Nordisk, Penumbra Inc., Philips, and SIS Medical; and served as a member of advisory boards for Amarin, Amgen, and Medtronic. D.P. received speaker’s fees from Daiichi Sankyo, outside the submitted work. D.P. is supported by a research grant from the Italian Ministry of Health (Grant: ‘Ricerca corrente’).