Should Intravascular Imaging Be Almost Routine in PCI?

September 12, 2023

A routine role for intravascular imaging (IVI) guidance for percutaneous coronary intervention (PCI) has long been favored by many of the technology's researchers and enthusiasts. Now evidence from large, randomized trials may be catching up with such aspirations, though not without caveats.

Recently unveiled studies collectively suggest that such IVI guidance, at least for PCI of more challenging lesions, can improve the effectiveness of coronary stent delivery in ways that directly lead to better outcomes.

One way IVI guidance may achieve that, the research suggests, albeit more speculatively, is by cutting risk for stent thrombosis compared with the risk associated with angiography-only PCI.

The new studies, two large randomized IVI trials plus a meta-analysis of 20 such studies, were presented August 27 in Amsterdam, Netherlands, at the European Society of Cardiology (ESC) Congress 2023.

In one, called ILUMIEN-4, PCI guided by optical coherence tomography (OCT) was associated with fewer procedural complications and better acute results — that is, larger post-PCI minimum stent area (MSA) — than in angiography-only procedures (P < .001). Post-stenting MSA, an established predictor of clinical outcomes, was the primary imaging endpoint of the trial with almost 2500 patients.

Yet the OCT group's greater post-PCI MSA did not translate to reduced risk for the primary clinical endpoint of 2-year target-vessel failure. Among secondary endpoints, however, stent thrombosis at some point during the follow-up was 64% less likely (P = .02) with OCT guidance than angiography-only PCI.

ILUMIEN-4, despite its neutral clinical result, still "strongly advocates" for PCI guidance by OCT, at least among patients like those in the trial, said principal investigator Ziad Ali, MD, DPhil. He based that largely on the strategy's greater postprocedure lumen areas in the trials, which are among "the strongest independent predictors for long term outcomes," said Ali, St. Francis Hospital & Heart Center, Roslyn, New York, at a press conference on IVI trials during the ESC Congress.

Selected Complex Lesion Type

In contrast, the OCTOBER trial, presented at the sessions back to back with ILUMIEN-4, saw OCT guidance lead to better clinical outcomes than angiography alone after PCI of bifurcation lesions, which normally can be a special challenge for operators.

In the trial, which entered about 1200 patients with such complex lesions, the 2-year risk for major adverse cardiac events (MACE) fell 60% after OCT-guided PCI compared with angiography-only procedures (P = .035).

The finding is novel for showing that OCT guidance in bifurcation PCI can make a significant clinical difference, said OCTOBER investigator Niels R. Holm, MD, at the same media presentation on IVI trials.

"Multiple studies have shown that OCT allows for optimization of bifurcation PCI, and our results confirm that such optimization may improve the patient's prognosis," said Holm, Aarhus University Hospital, Denmark.

ILUMIEN-4 and OCTOBER, both of which prespecified the Xience (Abbott) everolimus-eluting stent for the procedures, were published in the New England Journal of Medicine in tandem with their respective presentations at the ESC sessions.

Covering the Spectrum

A meta-analysis presented at the same ESC session compared IVI using either OCT or intravascular ultrasound (IVUS) with angiography-only PCI across 20 randomized trials with a total of more than 12,000 patients.

Significant outcomes for IVI guidance vs angiography alone included a 31% drop in risk for target-lesion failure, the primary endpoint. And this study, as well, showed a steep 52% reduction in risk for in-stent thrombosis with the IVI-guided approach.

And "for the first time" in IVI studies, "we demonstrated reductions in all-myocardial-infarction and all-cause death, the latter by 25%," Gregg Stone, MD, Icahn School of Medicine at Mount Sinai, New York City, said in presenting the meta-analysis. Stone is also the ILUMIEN-4 study chairperson.

"The routine use of OCT or IVUS to guide most PCI procedures will substantially improve patient event-free survival," he predicted, "enhancing both the long-term safety and effectiveness of the procedure."

Stone said that IVI guidance "should be standard of care, if not in all patients, then in most patients." Part of the rationale: PCI is unlikely to be improved much further by incremental gains in drug-eluting stent design. "That technology has almost plateaued." But there's yet room, he said, for "substantially improved outcomes" from adjunctive treatments and techniques such as IVI guidance.

The 20 studies in the meta-analysis encompassed an array of patients and lesions both complex and noncomplex, Stone observed, including bifurcation lesions, chronic total occlusions, left-main coronary stenoses, and MI culprit lesions.

"They really covered the spectrum of PCI," he said. "I'm not recommending that intravascular imaging be used in every single case. But I do think it should be used in the majority of patients" and be standard-of-care for PCI in left-main lesions and "complex coronary disease, high-risk patients, and high-risk lesions."

Unique Advantage

The IVI-guidance groups in both ILUMIEN-4 and the meta-analysis showed a significant drop in risk for stent thrombosis — that is, abrupt thrombotic vessel closure, which typically occurs in 1% or fewer PCI cases but can trigger an MI and pose a mortality risk up to 45%.

Those risk reductions are consistent with a unique IVI advantage: the ability to guide optimization of stent deployments. When formally presenting ILUMIEN-4 at the ESC sessions, Ali observed that IVUS and OCT imaging allows operators to identify and often correct less-than-ideal results of an initial stent delivery — such as residual gaps between stent struts and vessel wall — that may encroach on the lumen, with possible clinical consequences.

Such imaging, said Ali, "lets you identify tissue protrusions, malappositions, dissections, and untreated reference-segment disease" that may potentially trigger thrombosis. That makes a strong argument for giving IVI guidance a more common, perhaps even routine role in PCI procedures.

Selling Routine IVI-Guided PCI in Practice

"I think the study results are quite clear," said Deepak L. Bhatt, MD, MPH, as session co-moderator following the OCTOBER presentation. "The challenge, though, will be convincing the average interventional cardiologist worldwide that it was specifically the imaging and not the extra care that the patient getting OCT also inherently receives."

Did OCT's better trial outcomes stem from IVI itself or from greater operator attentiveness to procedural results — such as, for example, more high-pressure expansions to optimize stent placement, "the sort of thing that tends to occur when invasive imaging is added on to just plain old angiography?" Bhatt asked of Lene N. Andreasen, MD, who had just presented the OCTOBER trial. "There's no way of uncoupling the two things."

What can be said, "at this point, to convince interventional cardiologists that the extra time, energy, expense, is truly indicated," that the data are "sufficient to change global practice?" asked Bhatt, Mount Sinai Hospital and Icahn School of Medicine at Mount Sinai.

That remains an open question," acknowledged Andreasen of Aarhus University Hospital, Denmark. The best argument in favor of selective IVI-guided PCI is that "we actually see a clinical benefit" in the trials. "But of course, it comes with a cost. It comes with longer procedures and more contrast." How clinical practice responds to the new data remains to be seen, she proposed.

ILUMIEN-4 and OCTOBER in Detail

Conducted at 80 centers in 18 countries, ILUMIEN-4 randomly assigned patients with diabetes or complex coronary lesions to undergo PCI guided by OCT or using standard angiography only, 1233 and 1254 patients, respectively.

Post-PCI MSA averaged 5.72 mm2 with OCT guidance and 5.36 mm2 in the angiography-only group (P < .001).

Their rates of target-vessel failure at 2 years were not significantly different at 7.4% and 8.2%, respectively. The 2-year composite endpoint included cardiac death, target-vessel-related MI, or ischemia-driven target-vessel revascularization.

Definite or probable stent thrombosis was observed over 2 years in 0.5% of the OCT group and 1.4% of those with angiography-only PCI, for a hazard ratio (HR) of 0.36 (95% CI, 0.14 - 0.91; P = .02) favoring OCT.

The OCTOBER trial, conducted at 38 centers in Europe, entered 1201 patients with stable angina or acute coronary syndromes and angiographically identified complex bifurcation lesions. They involved the left-main coronary artery in about one-fifth of cases.

Patients were randomly assigned to bifurcation PCI guided by OCT or under standard angiography, 600 and 601 patients, respectively. Rates for procedure-related complications were similar at 6.8% and 5.7%, respectively.

Over a median of 2 years, 10.1% of the OCT group and 14.1% of angiography-only patients developed a MACE event, including cardiac death, target-lesion MI, or ischemia-driven target-lesion revascularization. The adjusted HR was 0.71 (95% CI, 0.51 - 0.98; P = .035) in favor of OCT.

Meta-analysis, Trials To Date

The meta-analysis presented by Stone included ILUMIEN-4, OCTOBER, and 18 earlier outcomes trials comparing PCI guided by IVI, either OCT or IVUS, and angiography-only PCI. It covered 12,428 patients with chronic or acute coronary disease and followed them a mean of 26 months; the longest follow-up was 5 years. They were assigned to IVI-guided or angiography-only PCI, 7038 and 5390 patients, respectively.

Stone and colleagues conducted a network meta-analysis of the 20 studies, that is, a combined analysis that allowed both direct and indirect comparisons of standard angiography-only procedures to each of the other studied comparator interventions including OCT, IVUS, and either OCT or IVUS. They then derived network-estimate odds ratios (OR) for IVI-guided PCI vs angiography-only procedures.

Network Estimate Odds Ratio (OR) for Outcomes, IVI-Guided vs Angiography-Only PCI
End points OR (95% CI)
Target-lesion failure* 0.69 (0.61 - 0.78)
Stent thrombosis 0.48 (0.31 - 0.76)
Any MI 0.82 (0.69 - 0.98)
Target-vessel revascularization 0.71 (0.61 - 0.84)
All-cause death 0.75 (0.60 - 0.93)
*Includes cardiac death, target-vessel MI, or target-lesion revascularization

"Hopefully, this will impact the guidelines," Stone said of the meta-analysis. Procedures guided by IVI might become more common in clinical practice if they were to garner a Class-I guideline recommendation, the strongest recommendation category, he speculated.

"That would make a difference, but we'd also need to work to remove impediments to increasing intravascular imaging guidance" for most patients undergoing PCI, he said, referring to challenges in obtaining reimbursement for IVI-guided PCI and training enough operators to handle the projected demand.

ILUMIEN-4 was funded by Abbott. OCTOBER was supported by grants from Abbott Vascular, St. Jude Medical, and Aarhus University. The network meta-analysis received statistical support from Abbott. Ali disclosed institutional grant support from Abbott, Abiomed, Acist Medical, Boston Scientific, Cardiovascular Systems, Medtronic, the National Institutes of Health, Opsens Medical, Philips, and Teleflex; consulting fees from Astra Zeneca, Philips, Shockwave; and holding equity in Elucid, Spectrawave, Shockwave, and VitalConnect. Holm disclosed institutional research grants from Abbott, Biosensors, Boston Scientific, and Medis; and speaker fees from Abbott, Cardirad, and Terumo. Stone disclosed research contracts from Abbott, Abiomed, Bioventrix, Cardiovascular Systems, Phillips, Biosense-Webster, Shockwave, Vascular Dynamics, Pulnovo, and V-wave; consulting for, receiving royalties from, or being employed by or holding equity interest in Abbott, Daiichi-Sankyo, Ablative Solutions, Robocath, Miracor, Vectorious, Valfix, TherOx, HeartFlow, Neovasc, Ancora, Elucid Bio, Occlutech, Impulse Dynamics, Adona Medical, Millennia Biopharma, Oxitope, Cardiac Success, HighLife, Cagent, Applied Therapeutics, Biostar family of funds, SpectraWave, Orchestra Biomed, Aria, and Xenter; and receiving honoraria for speaking from Medtronic, Abiomed, Amgen, and Boehringer Ingelheim. Bhatt's disclosures can be found at Andreasen has disclosed no relevant financial relatiohships.

European Society of Cardiology Congress 2023: Hot Line 4. Presented August 27, 2023.

N Engl J Med. Published online August 27, 2023. ILUMIEN Abstract, OCTOBER Abstract

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