Features of Complex CAD Carry Progressive Risk in PCI, Registry Confirms

Patients who have a higher number of complex anatomical characteristics—such as bifurcations, long stented length, and multivessel disease—have poorer 1-year outcomes post-PCI, data from the e-Ultimaster multicenter registry confirm.

A “stepwise increase” was observed as the risky features piled on, researchers reported recently in EuroIntervention.

Senior author Mamas Mamas, BMBCh, DPhil (Keele University, Stoke-on-Trent, England), told TCTMD that the “nut of the problem” is how best to define complexity. Here, they focused on lesion characteristics, he said, but a more-holistic perspective could take into account patient factors (eg, cancer, frailty) and procedural factors (eg, hemodynamic support, atherectomy).

“The problem is that depending on how you define complexity, you may have very different answers for your intervention. So often people think about whether we should be giving prolonged antiplatelet therapy for complex patients, balancing the risk of ischemic events and bleeding events. Of course, it very much depends on what the complex cohort you’re talking about is,” Mamas explained.

Nor is complexity a single entity. Rather, said Mamas, it’s incremental and different features carry different levels of risk. “We all lump complex lesions into one pot, but we’ve never really considered that there is a dose-response curve and the more complex features you have, the worse the risks are,” he observed.

“What I think is needed,” said Mamas, “is some sort of algorithm that says we will define complex PCI as anything that has a 30-day mortality of over 5%, 10%, whatever your percent may be. . . . I think it’s the right time for something like an academic research consortium to get people around the table and say, ‘What are we going to [consider] complex PCI?’” This process should be informed by data rather than opinion, he added.

For their study, the researchers framed “complexity” based on factors outlined by the 2016 pooled patient-level meta-analysis that helped inform the 2017 European guidelines for dual antiplatelet therapy (DAPT).

Gennaro Giustino, MD (Mount Sinai Hospital, New York, NY), lead author of that meta-analysis, said this paper “validates the complex PCI definition that was derived from randomized controlled trials of DAPT duration,” in that its registry findings echo what had been seen in the lower-risk, more-selected populations. He agreed that there is not a lot of consensus over how to define this concept, noting that they chose their features based on what RCT data were available in the evidence base. This is why they didn’t include atherectomy, mechanical circulatory support, and PCI of surgical grafts, for instance, which Giustino said also merit attention.

Cardiac Death, Target-Vessel MI, Clinically Driven TLR

Mamas, along with lead author Mohamed O. Mohamed, MBBCh (Keele University), conducted a post hoc subgroup analysis of data on 35,839 patients (mean age ~64 years; 75% men) who underwent PCI between 2014 and 2018, all receiving Ultimaster DES (Terumo Corporation).

Complex features included multivessel PCI, at least three stents, at least three lesions, bifurcation with at least two stents, total stent length of 60 mm or more, and chronic total occlusion (CTO). About one-quarter (27.3%) had at least one feature, with most having one or two (73.3%). Most common were multivessel PCI (16.3%), three or more stents (12.3%), and stented length of 60 mm or more (8.8%).

Patients in the complex PCI category tended to be older, be male, have more comorbidities, and have previously undergone revascularization. Compared to those without any complex features, their indication for PCI was more likely to be chronic coronary syndrome (52.8% vs 41.8%).

At 1 year, the risk of target lesion failure was significantly higher in patients with versus without such characteristics, with differences in cardiac death, target-vessel MI, and clinically driven TLR.

One-Year PCI Outcomes: Patients With vs Without Complex Features

As the number of these features increased, so too did the adverse-event risk. Apart from CTO, each feature was linked to higher risk of TLF and definite/probable stent thrombosis. Bifurcation lesions carried the highest 1-year risk of TLF (HR 2.01; 95% CI 1.55-2.62).

Bleeding rates were similar in the complex and noncomplex groups at 30 days. But at 1 year, bleeding as a whole was more common in patients who had complex features (2.4%) than in those who did not (2.0%; P = 0.03), as was BARC 3-5 bleeding (0.8% vs 0.5%; P < 0.01).

There are a few explanations as to why, the researchers say. “First, risk factors for ischemia (hypertension, diabetes, renal failure, and advanced age) also increase the risk of bleeding. Furthermore, complex PCI patients are more likely to receive prolonged DAPT therapy or more-potent P2Y12 agents, which may have contributed to their higher bleeding rates.”

To TCTMD, Mamas elaborated on the clinical implications. Trials such as GLOBAL LEADERS and TWILIGHT have suggested a benefit to adjusting DAPT, while many guidelines currently call for tailored approaches to antithrombotic strategies based on complexity, he pointed out. “But of course we have no clear definition for what we mean by complex. That makes it very challenging.”

No matter how it’s defined, though, complexity ups the risk of complications for patients undergoing revascularization, Mamas noted. It’s important to also understand what happens among patients who receive medical therapy instead. Yet oftentimes it is these challenging cases that are excluded from major trials.

For now, the best thing for operators to do when treating high-risk patients, he said, is “make sure the PCI results that we get [are] as good as possible. In my mind, that means using imaging, making sure your stent’s well opposed and adequately expanded, making sure there are no edge dissections, and so forth.” These patients might also benefit from prolonged or more-potent antiplatelet therapy, Mamas continued. “The fly in the ointment, however, is that we also show that these patients that have increased risk of ischemic events by virtue of [their type and] number of complex features also have increased bleeding risk,” so teasing out the risk-benefit ratio will be key.

Giustino said their original idea in choosing the six anatomical features was to create a way to gauge risk that would be easy to apply in practice. “It’s really not like a score. It’s based on criteria that put patients at higher risk,” so that post-PCI these people can receive extra monitoring or more intensive care, he stressed.

Unlike scores like SYNTAX, designed to guide revascularization strategy, Giustino emphasized that their definition was meant to “identify patients after the procedure. It is not helpful in deciding whether somebody should go for the procedure.”