Intravascular imaging to guide percutaneous coronary intervention of complex lesions: time to renovate guidelines?

Comment on ‘Intravascular imaging–guided or angiography-guided complex PCI’, which was published in the New England Journal of Medicine, https://doi.org/10.1056/NEJMoa2216607. This investigator-initiated, industry-funded, prospective, multicentre, randomized, open-label trial aimed to test the superiority of intravascular imaging-guided percutaneous coronary intervention (PCI) over angiography-guided PCI in patients with chronic coronary syndrome (CCS) or acute coronary syndrome (ACS) undergoing percutaneous treatment of complex coronary artery lesions. Complex coronary artery lesions were defined as: true bifurcation lesions, chronic total occlusions, unprotected left main disease, long lesions, multi-vessel disease, lesions requiring three or more stents, in-stent restenosis, severely calcified lesions, or ostial lesions of major epicardial vessels.1 The primary endpoint was target vessel failure (TVF), defined as a composite of cardiac death, target vessel myocardial infarction (MI), or clinically driven target vessel revascularization (TVR). Secondary endpoints included the individual components of the primary endpoint, TVF without procedure-related MI, a composite of target vessel MI or cardiac death, and definite stent thrombosis (ST). A total of 1639 patients with complex coronary artery lesions (mean age, 66 years; 21% female; 51% ACS) were enrolled from May 2018 through May 2021 at 20 sites in South Korea and were randomized in a 2:1 ratio to undergo intravascular imaging-guided PCI (n = 1092) or angiography-guided PCI (n = 547). Randomization was stratified based on clinical presentation and participating centre. The choice of intravascular ultrasound (IVUS) or OCT was left at the operators’ discretion, and imaging could be used at any time during the PCI procedure but was mandated after stent implantation to guide optimization. Intravascular imaging was performed with IVUS in ∼75% of cases and with OCT in the remaining cases. PCI was performed with the use of standard techniques for coronary lesion preparation and with implantation of everolimus-eluting stents. Clinical follow-up was conducted at 1 month, 6 months, and 12 months and yearly thereafter. Median follow-up was 2.1 years. The incidence of the primary endpoint was significantly lower in the intravascular imaging-guided PCI group than in the angiography-guided PCI group [cumulative incidence at 3 years, 7.7% vs. 12.3%; hazard ratio (HR), 0.64; 95% confidence interval (CI), 0.45–0.89; P = 0.008]. After excluding procedure-related MI events, the incidence of TVF remained lower in the intravascular imaging-guided PCI group than in the angiography-guided PCI group (cumulative incidence, 5.1% vs. 8.7%; HR, 0.59; 95% CI, 0.39–0.90). The cumulative incidence of cardiac death was lower in the intravascular imaging-guided PCI group than in the angiography-guided PCI group (1.7% vs. 3.8%, HR, 0.47, 95% CI 0.24–0.93), as well as that of TVR (3.4% vs. 5.5%; HR, 0.69; 95% CI, 0.40–1.18) and of the composite endpoint of target-vessel MI or cardiac death (5.3% vs. 8.5%; HR, 0.63; 95% CI, 0.42–0.93). The incidence of definite ST was low (0.3%) in the overall trial population, with a statistically uncertain difference between the two groups (0.1% vs. 0.7%; HR, 0.25; 95% CI, 0.02–2.75). No differences in the incidence of procedure-related safety events (e.g. peri-procedural MI, contrast-induced nephropathy) were observed between the two groups. Coronary artery disease (CAD) complexity largely influences the efficacy of revascularization procedures, and patients undergoing PCI of challenging subsets of lesions and more advanced CAD remain at increased risk of adverse ischaemic events in the mid- and long-term follow-up.2 Angiographic guidance of PCI is limited by the 2D representation of a complex 3D structure. Angiography, in fact, displays luminal dimensions and characteristics only, without providing information on atherosclerotic plaque phenotype and burden, and is often inadequate in identifying stent underexpansion, malapposition, or edge dissections.3 The lack of adequate procedural guidance can determine unpredictable and suboptimal PCI results, portending higher risk of adverse events during and after the procedure.2 These limitations are overcome, at least in part, by intracoronary imaging techniques (e.g. IVUS, or optical coherence tomography (OCT)) which enable high-resolution, real-time visualization of the coronary artery vessel lumen and plaque morphology, as well as of suboptimal stent findings, thus allowing to obtain precise measurements and stepwise assessment and optimization during complex PCI.4 Previous large observational cohort studies, randomized controlled trials (RCTs), and meta-analyses have demonstrated that IVUS-guided PCI is able to reduce major adverse cardiovascular events (MACEs),5,6 mostly due to a lower risk of repeat revascularization in the target vessel rather than to effects on hard endpoints such as cardiac death or MI. However, these trials had relatively small sample size, enrolled highly-selected lesion subsets, and relied on short-term follow-up. In contrast, data on long-term clinical outcome after OCT-guided PCI are limited, although previous RCTs showed comparable clinical outcomes with IVUS-guided PCI.7 Based on the available evidence, current guidelines recommend considering the use of intravascular imaging to optimize PCI in selected patients only (e.g. left main lesions, restenosis) with a IIa recommendation.8 Yet, the uptake of intravascular imaging for PCI guidance remains quite low worldwide (i.e. <15%) with wide variability among physicians and centres, partly due to costs and reimbursement issues.9 The RENOVATE-COMPLEX-PCI trial showed in a somewhat larger population of patients with complex CAD that intravascular imaging-guided PCI is associated with a reduced risk of TVF as compared with angiography-guided PCI.1 The point estimate of the effect size is consistent with that observed in previous trials.5,6 The clinical relevance of such findings is based on the long-term benefit of guiding PCI through intravascular imaging in terms of adverse clinical outcomes, without an appreciable excess in periprocedural complications. Yet, the trial was not powered to assess the individual components of the primary endpoint, thus preventing to elucidate the mechanisms underlying this prognostic advantage, which likely depends on a contribution of multiple trends observed for cardiac death, target-vessel MI, TLR, and definite ST in favour of an intravascular imaging strategy. Moreover, it should be emphasized that the true effect size of this advantage is statistically uncertain, as reflected by the wide 95% CI of the TVF reduction. This in turn is due to the small number of events (136, but only 88 TVF events without procedure-related MI) recorded in a low-risk population. Another important limitation of the trial is that invasive imaging was mandated only after PCI for stent optimization, so that about one fourth of enrolled patients did not receive baseline imaging investigation, which is important not only to plan adequate lesion preparation and stent sizing but also to assess atherosclerotic plaque phenotype providing opportunities for further risk stratification based on imaging criteria of vulnerability.4 Despite IVUS or OCT imaging could be performed after PCI in almost the totality of patients in the invasive imaging group, the pre-specified imaging criteria for stent optimization were achieved in only 45% of these patients, albeit a relatively conservative criterium for sufficient stent expansion (i.e. minimum stent area >80% of the respective mean reference lumen area) was used compared with that used in large ongoing trials of imaging-guided PCI.7 Whether higher rates of achieved stent optimization would have translated into greater clinical benefit compared with angiographic guidance remains unknown. Furthermore, only East Asian patients were included in the trial, of whom more than half were enrolled at a single centre, thus limiting the generalizability of the results. Finally, as the use of intravascular imaging increases procedural time, resource utilization, and costs of PCI as compared to angiography-guided PCI; future cost-effectiveness analyses are warranted to inform clinical decision-making. In conclusion, the RENOVATE-COMPLEX-PCI trial reinforces the role of intravascular imaging use for PCI optimization in patients with complex CAD. While this represents yet another clear evidence in support of IVUS use in this setting, more data are needed for OCT imaging (which was relatively underrepresented in this trial). If the upcoming results of two large RCTs designed to test the superiority of OCT-guided PCI vs. angiography-guided PCI in high-risk patients with complex lesions (i.e. ILUMIEN IV7 and OCTOBER10) will confirm these findings, the totality of the evidence in support of intravascular imaging use during PCI of complex lesions will likely justify an update of current clinical guidelines on revascularization. No new data were generated or analysed in support of this research.