Sirolimus Balloons Show Promise in Treating Coronary In-Stent Restenosis

For interventionalists hoping that a new generation of coronary balloons might improve treatment of in-stent restenosis (ISR), contemporary registry data were encouraging.

In a propensity score-matched analysis of 335 pairs of patients with ISR lesions, clinical outcomes were similar 2 years after treatment with thin-strut drug-eluting stents (DES) or the Magic Touch sirolimus drug-coated balloon (DCB):

• Target lesion revascularization: 11.6% vs 11.8% (P=0.329)
• Target vessel revascularization: 14.0% vs 13.1% (P=0.822)
• Myocardial infarction: 7.2% vs 4.5% (P=0.186)
• All-cause death: 5.7% vs 4.2% (P=0.476)
• Major adverse cardiovascular events: 21.5% vs 17.6% (P=0.242)

These results provide some information about the long-term efficacy and safety of sirolimus DCBs versus DES in real-world patients with DES-ISR, suggested Bernardo Cortese, MD, PhD, of DCB Academy and Fondazione Ricerca e Innovazione Cardiovascolare, both in Milan, and colleagues in Circulation: Cardiovascular Interventions.

The argument for DCBs in ISR is that they can deliver antiproliferative drugs to the restenotic lesion without the additional metal layer of a DES. There is a clinical need, as ISR occurs in 5% to 10% of cases of percutaneous coronary intervention (PCI) and is the most common cause of stent failure, according to Cortese’s group.

Magic Touch is currently being tested for coronary ISR in the randomized MAGICAL ISR trial. Meanwhile, the Selution SLR 014, another sirolimus DCB, is anticipated to have results in this setting soon from SELUTION4ISR.

“We await eagerly the results of these studies. All of this signifies that PCI continues to evolve in an effort to maximize benefits for the many millions of patients treated each year with PCI for symptomatic CAD [coronary artery disease],” wrote Aloke Finn, MD, of CVPath Institute in Gaithersburg, Maryland, and the University of Maryland in Baltimore, in an accompanying editorial.

Sirolimus is already the dominant coating for coronary DES when eluted from polymers. Part of the appeal of sirolimus for DCBs is its perceived safety relative to paclitaxel, the drug initially chosen for first-generation DCBs for its highly lipophilic properties, Finn noted

“However, questions remain about whether such an approach results in sustained drug levels and clinical antirestenotic efficacy,” he wrote. “DES tends to deliver therapeutic levels of sirolimus or its analogs for at least 60 to 90 days. It remains unclear if [sirolimus-coated balloons] can match these drug kinetics, and inferior sustained drug delivery would be expected to result in higher rates of [target lesion revascularization].”

Another downside to sirolimus DCBs is that they require more lesion preparation.

DCBs that release sirolimus are a relatively new invention, and they require researchers to engineer an effective release of this antiproliferative drug, given its limited lipophilicity inherently blocking effective vessel wall penetration.

“To ensure adequate inhibition of neointimal proliferation, sirolimus is released from the stent for several months,” Cortese and colleagues explained. “Therefore, for balloon-based delivery of sirolimus, it was necessary to develop some form of delayed-release technology to overcome the above limitations and to ensure adequate antiproliferative treatment.”

This study was based on a pooling of registry records on patients who underwent PCI for DES-ISR, including those who received a Magic Touch sirolimus DCB in the EASTBOURNE registry (from sites in Europe and Asia) and those who received thin-strut DES in the DEB-DRAGON registry (from Poland).

The study included 1,545 patients (median age 68-69, 68%-81% men) with 1,679 ISR lesions. This was a complex group of patients, given that 38%-45% had diabetes, 13%-18% had chronic kidney disease, and 51%-53% had acute coronary syndrome.

Of these participants, 40.2% had been treated with thin-strut DES and 59.8% had been treated with Magic Touch.

The DES group tended to be younger and female, and had lower prevalence of diabetes, previous coronary bypass surgery, and multivessel disease. However, they had more hypercholesterolemia, chronic kidney disease, and congestive heart failure, and presented more frequently with unstable angina compared with the sirolimus DCB arm.

Cortese and colleagues tried propensity-score matching to make the two groups more comparable, but acknowledged the inherent limitations of a non-randomized analysis. What’s more, the two registries came from different centers that did not follow a uniform protocol for lesion preparation.

As such, “lesion assessment as well as angiographic and procedural data might not be fully accounted for,” Finn cautioned. This study, he said, “cannot reliably inform us about the relative safety of these different strategies given differences in operator technique and lack of information about peri-procedural myocardial infarction.”

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