Treating In-Stent CTOs May Be Riskier Than De Novo CTOs Despite Similar Procedural Success

Intervening on patients with chronic total occlusions (CTOs) can be done safely by experienced operators, but in-stent blockages are associated with double the incidence of MACE when compared with de novo lesions, according to new registry data.

Less than a month after the presentation of the DECISION-CTO study that pitted CTO revascularization against optimal medical therapy—with less than exciting results for interventionalists—new results in this field are welcome to physicians hoping to learn more about this hard-to-study condition, say experts.

The study likely doesn’t change much, “but it does add to the whole field of chronic total occlusion intervention that suggests based on this, coupled with DECISION-CTO, the bar needs to be raised a little bit higher for when to intervene in these patients,” said Howard Herrmann, MD (University of Pennsylvania Perelman School of Medicine, Philadelphia), who was not involved in the study.

“What I always tell my fellows is to remember when we're looking at CTOs is that the C stands for chronic,” he told TCTMD. “One has to be sure that the patient is going to actually benefit from the intervention, either in terms of survival because there’s a large ischemic hibernating area of myocardium or [in terms of] quality of life due to improvement in angina, and to be relatively sure that we’re not just performing cosmetic surgery.”

One has to be sure that the patient is going to actually benefit from the intervention . . . and to be relatively sure that we’re not just performing cosmetic surgery. Howard Herrmann

For the current study, Stéphane Rinfret, MD, SM (McGill University Health Centre, Montreal, Canada), and colleagues looked at 899 patients with CTOs—12.3% with in-stent lesions—from three high-volume European and Canadian centers between 2009 and 2015. Results published online April 12, 2017, ahead of print in JACC: Cardiovascular Interventions show that procedural success was 86.5% both in patients with in-stent lesions and in those with de novo lesions, with rates of major procedural complications that were low and similar in the two groups.

After a median follow-up of 471 days, the primary endpoint of MACE (cardiac death, target-vessel MI, and ischemia-driven TVR), was numerically but nonsignificantly higher among patients with in-stent compared with de novo CTO lesions (20.8% vs 13.9%; P = 0.07), driven by more frequent TVR in the in-stent arm (16.7% vs 9.4%; P = 0.03). There were no differences with regard to cardiac death and target-vessel MI.

Moreover, on multivariate analysis, in-stent CTO was an independent predictor of MACE (HR 2.16; 95% CI 1.18-3.95), as was post-CABG status, increased estimated glomerular filtration rate, ACS presentation, a higher number of diseased vessels, and a higher PROGRESS-CTO score.

The pathophysiology of in-stent occlusions is “largely unknown,” but they are likely caused by other factors such as stent thrombosis, stent fracture, or neoatherosclerosis, Rinfret and colleagues write. “The improvement in clinical outcomes for [in-stent] CTO patients will likely stem from the development of newer-generation DES, with better antiproliferative characteristics as well as eliciting lower inflammatory response,” they say.

IVUS can also provide “useful information” regarding the underlying mechanisms of in-stent CTOs, they add, acknowledging that its use was “low” in the study (12.9% overall), likely “in order not to prolong these already lengthy procedures and due to cost-related issues.”

Guessing at Mechanisms

In an accompanying editorial, Dimitri Karmpaliotis, MD, PhD, and Raja Hatem, MD (Columbia University Medical Center, New York, NY), write that in-stent CTO lesions “still represent a challenge” despite improvements in CTO revascularization overall. The strengths of the current report include the large sample size and the availability of data on long-term clinical outcomes, which makes this observational study relevant to contemporary practice, but the editorialists say there was a “missed opportunity” to discover more about the mechanisms of in-stent CTO because of the lack of IVUS.

The increased TVR rate associated with in-stent CTO revascularization means operators have to set realistic expectations with their patients, according to Karmpaliotis and Hatem. If patient and physician decide to proceed, “it is imperative to strive for the best procedural outcomes through the use of multimodality imaging to understand the etiology of the prior stent failure and subsequently utilize adjunctive methods to optimize stent expansion, such as laser or rotational atherectomy,” they advise.

Other things to consider would be the use of drug-eluting balloons, current-generation DES, or brachytherapy, or allocation of the patient to optimal medical therapy in the case of “long stents with poor outflow or small-diameter, single-vessel runoff.”

In-stent CTO “remains a challenging lesion subset and has to be dealt with [with] the utmost care and precaution,” the editorialists conclude. “However, this lesion subset can and should be tackled by taking the extra time and effort to apply meticulous PCI technique during the index procedure.”

Not Practice Changing, but Lessons to Be Learned

While the study’s results are likely not substantial enough to change Herrmann’s practice, he said he still wants “to have a conversation with the patient about their expectations in terms of success and recurrence.” For now, operators need to “use studies like DECISION-CTO, even though it's not a perfect study, and others that go the other way in terms of their conclusions to decide whether to intervene,” he added. “But in general, [outcomes are] a little worse for the stent patients, so that has to be part of the discussion.”

Future studies should “stratify for de novo versus in-stent CTO since they do behave differently,” Herrmann suggested.

Also commenting on the study for TCTMD, Ravi Dave, MD (UCLA Medical Center, Santa Monica, CA), said lessons learned from the study are significant. “It is important to know especially from this particular study that a chronic total occlusion within a stent is more challenging and it tends to have not as good success rates as others and you need to do something different,” he said. In his discussions with patients, Dave said he will likely cite this paper now to realistically adjust their expectations before the procedure.

Despite the already well-known challenges of studying CTO lesions (eg, recruiting enough patients, including different centers with substantial expertise, and maintaining consistency in procedures and care), Dave said that more studies are needed. “One thing that we can learn from this study is that if a patient is going to have an angiogram done who has previously had a stent and you're suspecting a CTO, you would probably tell the patient that if there is a CTO anywhere outside the stent, you should have a good outcome. But if it is within the stented area, the success rate is slightly lower,” he concluded.