STAR Trial Gives Insight Into Two-Stage CTO PCI in Complex Patients

For patients with complex chronic total occlusion (CTO) lesions undergoing bailout PCI, a two-stage intervention alongside a strategy of subintimal tracking and reentry (STAR) leads to good technical success regardless of whether the second procedure was done within 2 or 4 months, according to new randomized data.

In the STAR trial, published online last week in JACC, Lorenzo Azzalini, MD, PhD (University of Washington, Seattle), and colleagues did not report a statistical difference in partial technical success of the staged procedure between those who received it 5-7 or 12-14 weeks following STAR (83.6% vs 71.4%; P = 0.08). However, the early group did see an advantage on the secondary endpoint of TIMI flow grade 2-3 in the target vessel at the start of the staged procedure (64.4% vs 44.2%; P = 0.012).

The findings give renewed support for shifting the paradigm of CTO PCI to two procedures to improve stent patency and outcomes among patients with the most complicated lesions, say researchers. They follow similar data from the nonrandomized INVEST-CTO study showing that staged PCI could enhance safety.

To TCTMD, Azzalini said he was surprised by the results because previous studies intimated that waiting at least 60 days for the second procedure after STAR led to better outcomes. He has now changed his practice based on these new results. “For practical reasons, we now encourage patients to come back sooner than later,” he said. “It’s easier to get the patient’s overall care journey completed in a more expedited fashion, which is also more compatible with life plans.”

Antonio Colombo, MD (Columbus Hospital, Humanitas Research Hospital, Milan, Italy), invented the STAR strategy, which involves creating a “purposeful dissection” by advancing a polymer-jacketed guidewire in the subintimal space until it reenters the true lumen distally, often at bifurcation points, with the goal of opening difficult-to-cross lesions.

“The drawback of this procedure is that many people have been stenting excessively, placing long stents, and by doing this approach, the long-term results are not acceptable,” Colombo told TCTMD. “If you refrain from stenting, as this article says, [and] you relook at a later time, . . . you may find better areas where to place a short stent and you avoid a long stent, and the long-term results are better.”

He said his hunch all long has been that an earlier second procedure would be better. “I am quite pleased to see that [in] this study, even if it did not reach a clear statistical value, the trend was in favor for an early follow-up,” he said. “So, I believe that if your acute results are not satisfactory and you want to improve, you have to do an early follow-up as this study seems to confirm.”

The STAR trial “doesn’t [give] the final word, but I believe the trend is clear,” Colombo continued, adding that a larger trial likely would have reached statistical significance.

STAR Findings

The trial, conducted at six centers in the United States, randomized 150 patients (mean age 65.8 years; 17.3% women) undergoing CTO PCI with STAR to receive early (n = 73) or late (n = 77) staged PCI between January 2022 and August 2024. All patients received STAR as a bailout strategy following an unsuccessful index attempt at CTO PCI, and the mean J-CTO score was 2.9.

Lesions were most often located in the right coronary artery (52.7%), followed by the circumflex (24.7%) and left anterior descending (22.7%) arteries. The estimated occlusion lengths were 37.3 and 39.7 mm in the early and late cohorts, respectively. About two-thirds of all lesions were calcified, and about one-quarter were reattempts at procedures that previously failed.

While partial technical success—defined as TIMI flow grade 2-3 with < 30% residual stenosis into at least one ≥ 2.5 mm distal branch—trended higher in the early group, there was no difference in the secondary endpoint of complete technical success (67.1% vs 61.0%; P = 0.44).

Overall MACCE rates were similar between the early and late groups (6.8% vs 3.9%; P = 0.49) and were driven by clinical perforations, eight of which occurred during the index procedure and two during the staged procedure. There were no instances of in-hospital death or need for emergency surgery in either group, with one stroke occurring following a staged procedure.

Most staged PCI procedures utilized antegrade wiring (64.4%) but also used were Stingray-based antegrade dissection and reentry (Boston Scientific; 6.5%), retrograde approaches (20%), and repeated STAR (5.3%).

On multivariate analysis, there was a trend toward a greater likelihood of partial technical success with early versus late staged stenting (OR 2.15; 95% CI 0.93-4.97).

“We need to make this procedure more attainable to more operators,” Azzalini argued, noting that previous proctoring initiatives have had a limited return on investment. “Many feel that there are huge barriers: it’s too technically complex [and] administrations many times are not supportive of a long procedure with higher complication rate.”

As such, other strategies are needed to enable more interventionalists to perform CTO PCI, he said. “I think that STAR is a step in that direction and it can a little bit democratize the access to high-level results to a wider population of operators,” Azzalini continued, adding that it should only be used after multiple other CTO strategies have been exhausted.

“I really hope that our data will promote a revolution in the field of CTO PCI,” he said. “This is the first randomized trial comparing different technical approaches to CTO PCI, and it is a field that has traditionally been informed by a lot of retrospective studies. This trial was rigorously conducted [and provides] solid data, and we should embrace this data to improve our patient outcomes.”

Future Directions

In an accompanying editorial, Yousif Ahmad, MD, PhD (University of California, San Francisco), Rohin K. Reddy, MBBS (Imperial College London, England), and Ajay J. Kirtane, MD (Columbia University Irving Medical Center/NewYork-Presbyterian, New York, NY), agree that “randomized trials within the CTO PCI field are rare, mirroring a pattern seen more broadly with most procedural strategies or techniques.

“The fact that these data demonstrated converse findings to the a priori study hypothesis serves to highlight the value of conducting strategy trials to inform clinical practice,” they stress.

While the trial is subject to some limitations, including its small size and the likelihood of not including patients who had severe complications during the index CTO procedure, the editorialists say, it highlights the importance of “not rely[ing] solely on intuition and biological plausibility to inform treatment strategies.”

Effective “immediately,” the clinical practice of CTO PCI should change based on these results, they say. “CTO PCI may require two procedures to ensure an optimal outcome in terms of both safety and efficacy, with the potential to avoid higher-risk strategies during the initial procedure,” they write. “Many of us have been waiting longer to bring patients back for staged procedures, based on expert consensus and perceived wisdom. STAR suggests this is likely not the correct approach.”

Next, Azzalini said he’d like to see a randomized comparison between up-front STAR and staged PCI versus conventional single-procedure approaches. “This trial should be powered to evaluate differences in both success and complication rates,” he noted.

“Another important topic of research is to figure out when . . . patients can be stented during the index STAR procedure, so that we don’t necessarily need to bring them back for staged PCI,” Azzalini continued. “Indeed, during the STAR trial, we noticed that several cases [had] an excellent final result of the initial procedure [that] was maintained at angiographic follow-up. One wonders whether we could optimize the patient flow through the healthcare system by just stenting them during the index procedure.”

Colombo, too, would like to see more research with this technique, but warned against using it in the left anterior descending artery where there are often many, especially septal, side branches that could be occluded.

Also, “we still do not know the effect of a drug-coated balloon in the subintimal space,” he said. “So, I think these should be done in a controlled study and maybe utilizing a sirolimus drug-coated balloon rather than a paclitaxel drug-coated balloon.”