Intravascular ultrasound-guided or angiography-guided complex high-risk PCI – The IVUS CHIP trial
Reported from ACC.26
Daniele Giacoppo reports and provides his perspective on the main results of the IVUS-CHIP trial, presented by Roberto Diletti from the Erasmus University Medical Center, Rotterdam, the Netherlands, during a Late-Breaking Trials session at the ACC.26 in New Orleans, and simultaneously published in the New England Journal of Medicine.
Why this study? – The rationale
Current European guidelines recommend the use of intravascular ultrasound (IVUS) and optical coherence tomography to guide percutaneous coronary intervention (PCI) in complex coronary artery disease, based on randomized trials predominantly conducted in East Asia and comprehensive meta-analyses.
Intravascular imaging is considered the reference standard for guiding PCI in complex coronary artery disease by ensuring adequate stent expansion, strut apposition, and plaque coverage, as well as enabling early detection of suboptimal results that may lead to stent failure. However, the results of previous randomized trials on the topic were heterogeneous, high-quality evidence from current European practice is limited, and the use of intravascular imaging remains low.
The IVUS-CHIP trial was designed to address the question of whether high-definition IVUS-guided PCI for complex coronary artery disease improves clinical outcomes compared with angiography alone in the context of a European population.
How was it executed? – The methodology
IVUS-CHIP was a multicentre, open-label, assessor-blinded, event-driven, randomized, clinical trial conducted at 37 centres across seven European countries.
Patients admitted for non-ST-segment elevation acute coronary syndrome or stable ischaemic heart disease who were scheduled to undergo PCI of one or more angiographically defined complex coronary lesions, or who had an indication for PCI with planned mechanical circulatory support, were randomly assigned in a 1:1 ratio to procedural guidance with IVUS or angiography alone. Randomization was stratified by participating centre and clinical presentation.
Complex coronary artery disease was defined as the presence of lesions with severe calcifications, chronic total occlusions, lesions involving the left main, true bifurcation disease with a side branch of at least 2.5 mm in diameter, ostial lesions of an epicardial vessel, in-stent restenosis, or lesions longer than 28 mm. In cases of chronic total occlusion, randomization was performed after successful lesion crossing. IVUS was to be performed with motorized pullback only and target lesions were to be treated with everolimus-eluting platinum-chromium stents only. Whereas IVUS assessment before PCI and after target lesion preparation was only recommended, post-PCI IVUS assessment was mandatory. Prespecified stent optimization criteria included assessment of geographic miss or missed focal lesions, edge dissections > 3 mm, minimum stent area (MSA) < 5 mm2 or < 90% of the distal reference lumen area in non-left main lesions, MSA < 8 mm2 at the body or < 7 mm2 at the polygon of confluence in left main lesions, MSA < 6 mm2 in left anterior descending lesions, MSA < 5 mm2 in left circumflex lesions, and plaque burden > 50% at stent edges.
The primary endpoint was target vessel failure, defined as a composite of cardiac death, target vessel myocardial infarction, or clinically indicated target vessel revascularization. If a statistically significant difference was observed for the primary endpoint, key secondary endpoints were to be tested in a prespecified hierarchical sequence to control the type I error. These secondary endpoints were a composite of target vessel myocardial infarction or target vessel revascularization; clinically indicated target vessel revascularization; a composite of cardiac death or target vessel myocardial infarction; target lesion failure defined as a composite of cardiac death, target vessel myocardial infarction, or clinically indicated target lesion revascularization; target lesion revascularization; and all-cause death. All outcomes were assessed at the longest available follow-up according to the intention-to-treat principle.
A sample size of 2,020 patients and 169 target vessel failure events at 18 months were estimated to provide 80% power to detect a 4% absolute risk reduction with IVUS-guided PCI (12%) compared with angiography-alone (8%) at a two-sided α of 0.05.
The trial was investigator-initiated and received an unrestricted research grant from the manufacturer of the IVUS catheter.
What is the main result?
A total of 2,020 patients were randomized to IVUS-guided PCI (n=1,010) or angiography-guided PCI (n=1,010) from November 2021 through August 2023. One patient in the angiography-guided PCI group was excluded from the analysis for having undergone randomization twice.
Baseline clinical and procedural characteristics were apparently balanced between groups. The mean age of the patients was 69 years, 21.6% were female, 31.3% had diabetes, 30.5% had a prior myocardial infarction, 47.2% had undergone prior PCI, 7.3% had undergone prior coronary artery bypass grafting, and 27.4% presented with an acute coronary syndrome. The mean SYNTAX score per patient was approximately 25 ± 14 in both groups and the mean number of target lesions per patient was approximately 1.4 ± 0.7 in both groups. The most common complex lesion types across procedures were lesions with severe calcification (44.0%) and lesions longer than 28 mm (60.9%). Left main disease was observed in 18.7% of procedures, true bifurcation disease in 32.7%, and chronic total occlusions in 22.1%. PCI with mechanical circulatory support was performed in 0.7% of procedures. IVUS was performed in 98.7% of procedures in the IVUS-guided PCI group and 0.9% of the patients in the angiography-guided PCI group. Procedural complications occurred in 11.3% of procedures in the IVUS-guided PCI group and 10.2% of procedures in the angiography-PCI group.
Complete follow-up information was available for 95.9% of patients. At a median follow-up of 19 months (interquartile range 15.2-23.4), target vessel failure occurred in 140 patients (13.9%) in the IVUS-guided PCI group and 112 patients (11.1%) in the angiography-guided PCI group (hazard ratio [HR] 1.25, 95% confidence interval [CI] 0.97-1.60, P=0.08). No significant differences between treatment groups were observed across key secondary endpoints and individual secondary endpoints. Cardiac death occurred in 34 patients (3.4%) in the IVUS-guided PCI group and 27 patients (2.7%) in the angiography-guided PCI group (HR 1.22, 95% 0.75-2.05). Target vessel myocardial infarction occurred in 66 patients (6.5%) in the IVUS-guided PCI group and 58 (5.7%) patients in the angiography-guided PCI group (HR 1.13, 95% 0.80-1.61). Clinically indicated target lesion revascularization occurred in 75 patients (7.4%) in the IVUS-guided PCI group and 61 patients (6.0%) in the angiography-guided PCI group (HR 1.22, 95% CI 0.87-1.71). However, definite or probable stent thrombosis (0.5% vs 1.5%; HR 0.33, 95% 0.12-0.90) and definite stent thrombosis (0.2% vs 1.0%; HR 0.20, 95% 0.04-0.90) were significantly lower in the IVUS-guided PCI group compared with the angiography-guided PCI group.
Critical reading and its relevance for clinical practice
Interpreting the results of the IVUS-CHIP trial and reconciling its major conclusions with the existing body of evidence is challenging. This trial, designed to demonstrate the superiority of IVUS-guided PCI in complex lesions compared with angiography alone, did not show significant differences in the primary endpoints as well as in the key secondary endpoints. Notably, there was a consistent numerical increase in event rates in the IVUS-guided PCI group compared with the angiography-guided PCI group across outcomes. Although these trends may reflect chance and do not support any conclusion of harm associated with IVUS guidance, they are largely unexpected, particularly given that the trial enrolled only patients with complex coronary artery disease, a population with established higher risk of stent failure and major ischaemic events compared with non-complex coronary artery disease. The lower incidence of stent thrombosis in the IVUS-guided PCI group may be explained by improved stent expansion and apposition, as well as early detection of relevant stent edge dissections compared with angiography alone. However, the magnitude of this benefit remains modest in absolute terms and is not paralleled by differences in other major ischaemic outcomes.
In this context, it should be recognized that no standardized and universally accepted definition of complex coronary artery disease currently exists, and randomized trials frequently rely on heterogeneous, study-specific criteria. Consequently, drawing robust conclusions regarding the impact of intravascular imaging guidance on outcomes in complex coronary artery disease remains uncertain, as each type of lesion encompasses multiple phenotypes with distinct procedural and prognostic implications. Left main and bifurcation disease patterns vary substantially according to lesion distribution across the bifurcation components, reference vessel diameters, side branch angulation, and disease length. Chronic total occlusions likewise exhibit marked anatomic heterogeneity, including differences in proximal cap morphology, calcification burden, obstruction length, tortuosity, and collateral circulation, all of which influence outcomes. In-stent restenosis lesions also differ considerably with respect to restenotic pattern, number of recurrences, underlying stent type, and histopathologic features. These considerations are further complicated by the varying overlap among complex lesion types; for example, left main lesions may also present as true bifurcation disease and exceed 28 mm in length.
In the IVUS-CHIP trial, the most prevalent types of complex coronary artery disease were lesions longer than 28 mm and those with severe angiographic calcification. The 28-mm threshold may have been insufficiently stringent to discriminate truly complex disease, potentially leading to the inclusion of lesions of lower complexity compared with left main disease, true bifurcation lesions, or chronic total occlusions. In contrast, severe calcification represents a clinically relevant technical challenge. However, in this trial, severity grading was based on angiography and the operator’s subjective assessment. It is well established that coronary angiography may inadequately characterize severe calcification, and reliance on subjective evaluation may have introduced bias. Notably, although severe calcification was reported in nearly half of procedures, the use of adjunctive plaque-modifying techniques, such as rotational atherectomy, orbital atherectomy, or intravascular lithotripsy, was relatively low.
Beyond anatomic complexity, procedures involving complex coronary artery disease subsets often require advanced techniques, specialized devices, and high operator expertise, thereby introducing additional variability compared with less complex scenarios. In this regard, it should also be considered that ILUMIEN IV, the largest, long-awaited trial on intravascular imaging, and OPTIMAL, another trial presented during the American College of Cardiology 2026 congress comparing IVUS-guided PCI with angiography-guided PCI for the treatment of left main disease, failed to demonstrate the superiority of intravascular imaging over angiography alone. Interestingly, IVUS-CHIP and these trials were conducted in Western countries, and their neutral results contrast with those of other trials such as RENOVATE-COMPLEX-PCI, IVUS-ACS, ULTIMATE, and OCCUPI, all conducted in East Asia and consistently favouring intravascular imaging over angiography. These observations may reflect geographic differences in experience and expertise with the interpretation of intravascular imaging.
In conclusion, the results of the IVUS-CHIP trial suggest that the benefits of intravascular imaging cannot be broadly generalized, and further analyses are warranted to elucidate the reasons for the substantial heterogeneity in findings across randomized trials, thereby enabling more predictable outcomes.
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