In this issue of Cardiology, Kalsi and colleagues report the results of a study-level meta-analysis encompassing 336,649 patients from 8 trials investigating the effects of intravascular ultrasound (IVUS)-guided versus angiography-guided primary percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI) [1]. In this aggregate-data meta-analysis, IVUS-guided PCI was associated with an 18% relative risk reduction in trial-defined major adverse cardiovascular events (risk ratio [RR], 0.82; 95% confidence interval [CI], 0.76–0.90) compared with angiography-guided PCI. In the overall cohort, IVUS-guided PCI was associated with a significant reduction in the risk of death (RR, 0.58; 95% CI, 0.35–0.98), target vessel revascularization (TVR; RR, 0.82; 95% CI, 0.71–0.95), and myocardial infarction (MI; RR, 0.58; 95% CI, 0.70–0.93). A numerical reduction of stent thrombosis (ST; RR, 0.61; 95% CI, 0.29–1.31) was also observed with IVUS-guided PCI. The results remained mainly consistent by excluding studies with bare-metal stent or unclear stent type with the exception of MI and TVR rates, which were only numerically lower with IVUS-guided compared with angiography-guided PCI.

The results of this study are in line with a recent network meta-analysis including 15,964 patients (n = 22 trials) with chronic or acute coronary syndrome (ACS) randomly assigned to either intravascular imaging (by IVUS or optical coherence tomography [OCT])-guided or angiography-guided PCI) [2]. At a mean follow-up of 24.7 months, intravascular imaging-guided PCI was associated with a 29% relative risk reduction of target lesion failure, mainly driven by a 45% risk reduction in cardiac death, 18% reduction in target vessel MI, and 28% reduction in target lesion revascularization (TLR) compared with angiography-guided PCI. The risk of ST was also reduced with IVUS or OCT compared with angiography-guided PCI [2]. The results remained consistent irrespective of the intravascular imaging modality (IVUS vs. OCT) [2].

The authors of the present meta-analysis should be commended for having provided additional insights on the effects of IVUS-guided PCI in patients with STEMI undergoing primary PCI. However, the results of this study should be interpreted in light of the following considerations.

First, this is an aggregate-data meta-analysis, and, in the absence of individual patient data, the impact of potential confounders on study results could not be appraised. Second, endpoint definitions varied largely across the included studies, with some studies including TLR in the composite major adverse cardiovascular event endpoint, while others included TVR or ST but not TLR. Therefore, the precise estimate of the treatment effect of IVUS-guided over angiography-guided PCI on primary and secondary endpoints could not be established. Third, a moderate heterogeneity between studies for death (I2 = 58%) was observed, suggesting that the mortality benefit with IVUS-guided PCI observed in this study should be interpreted with caution. However, this finding is in line with a recent meta-analysis including patients with either ACS or chronic coronary syndrome [2], demonstrating that intravascular imaging-guided PCI is associated with lower mortality than angiography alone. Although this study was not designed to discern the mechanisms by which IVUS-guided PCI improves events-free survival, intravascular imaging was associated with significantly lower risk of MI and repeat revascularizations which have been previously associated with higher mortality risk [3]. Fourth, the included studies largely differed in operators’ expertise, PCI techniques, data collection, events adjudication, and follow-up durations.

This study, alongside accumulating evidence, supports the concept that IVUS, and intravascular imaging in general, should represent a mainstay of modern coronary interventions – also in the context of primary PCI for STEMI. The 2023 European Society of Cardiology ACS guidelines recommend the use of intracoronary imaging for PCI guidance (class of recommendation IIA), while a class of recommendation IIB is provided for patients with ambiguous culprit lesions [4]. Similarly, the 2021 American College of Cardiology/American Heart Association guidelines on coronary revascularization recommend that intracoronary imaging should be considered among patients undergoing PCI (class of recommendation IIA), especially in complex lesion subsets [5].

The clinical advantages of IVUS during primary PCI reside in multiple aspects. First, IVUS might support operators in the identification of culprit lesions in patients with ACS when angiography alone remains inconclusive. Second, IVUS allows an optimal characterization of coronary lesions, prompting the use of advanced plaque modification techniques and detecting potential drug-eluting stent (DES) malapposition or underexpansion [6]. Notably, the additional value ensured by IVUS resulted in the change of PCI strategy in a not negligible proportion of patients (up to 74%) in the ADAPT-DES study [7].

Some advantages of IVUS-guided PCI are also shared by OCT, which has been recently shown noninferior to IVUS-guided PCI with respect to the composite endpoint of cardiac death, target vessel-related MI, or ischemia-driven TVR [8]. OCT has an inherently higher resolution, allowing a better plaque characterization and thrombotic material quantification in patients with ACS. In particular, the detection of plaque erosion is possible almost solely by OCT [9]. However, OCT requires vessel clearance by contrast dye injections, which increase the risk of acute kidney injury, especially in patients at higher risk of renal impairment such as those with STEMI. Taking into account the prognostic significance of contrast-associated acute kidney injury, this aspect should be taken into account in the selection of the intravascular imaging modality in STEMI patients [10]. Yet, definite data on the comparative effectiveness and safety of OCT versus IVUS-guided PCI in STEMI patients are still lacking.

The value of intravascular imaging may be even enhanced in complex and high-risk patients undergoing PCI, especially considering that stent malapposition may occur in up to 30% of STEMI patients [11]. Potential mechanisms of this phenomenon reside in high residual thrombotic material inside the vessel and/or vessel diameter underestimation by angiography alone. The use of intravascular imaging may overcome such limitations by prompting a more liberal use of thrombectomy techniques [12] and thus optimizing DES implantation.

In conclusion, IVUS-guided PCI is associated with improved survival and freedom from major adverse events, enhancing the long-term effectiveness of coronary interventions. The compelling evidence of a meaningful benefit with intravascular imaging guidance during PCI support its routine use in patients with STEMI who are at higher risk of adverse events. Further efforts are needed to overcome remaining barriers to the routine use of intravascular imaging, including training and reimbursement issues.

M.V. reports grants and/or personal fees from AstraZeneca, Terumo, Alvimedica/CID, Abbott Vascular, Daiichi Sankyo, Bayer, CoreFLOW, Idorsia Pharmaceuticals-Ltd, Universität Basel Department Klinische Forschung, Vifor, Bristol-Myers-Squib SA, Biotronik, Boston Scientific, Medtronic, Vesalio, Novartis, Chiesi, and PhaseBio, outside the submitted work. The other authors report no relationships relevant to the contents of this paper to disclose.

No funding was received for this commentary.

A.L. and A.M. wrote the first draft of the manuscript. M.V. critically reviewed the manuscript for important intellectual content.

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