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Although less effective for in-stent restenosis (ISR) than other lesions, contemporary zotarolimus-eluting stents (ZES) are safe and achieve rates of repeat revascularization comparable to those of other drug-eluting stents (DES) for this difficult lesion subset, according to a study published online August 14, 2013, ahead of print in JACC: Cardiovascular Interventions. Moreover, ZES perform just as well in DES restenosis as in bare-metal stent (BMS) restenosis.

Investigators led by Gert Richardt, MD, of Herzzentrum, Segeberger Kliniken (Bad Segeberg, Germany), focused on cases of in-stent restenosis among 3,489 patients pooled from the randomized RESOLUTE All Comers (RAC) trial and the RESOLUTE International (RINT) registry. Both studies involved treatment of all comers with Resolute, a contemporary thin-strut, cobalt-chromium stent with a biocompatible coating that elutes zotarolimus (Medtronic Vascular, Santa Rosa, CA).

Overall, 8.1% of patients (n = 281; 91 from the RAC trial and 190 from the RINT registry) received ZES for ISR. At 1 year there were no differences in outcomes between patients treated for in-stent restenosis or other lesion types, although a trend was seen toward more overall and late Academic Research Consortium-defined stent thrombosis with in-stent restenosis.

Repeat Revascularization More Common in ISR

At 2 years, however, the ISR group experienced higher rates of TLF (cardiac death, target vessel MI, and clinically driven TLR), clinically driven TLR, and MACE (death, MI, emergent CABG surgery, or clinically driven TLR), as well as a trend toward more definite or probable stent thrombosis (table 1). However, rates of cardiac death or target-vessel MI were similar between the lesion groups.

Table 1. Clinical Outcomes at 2 Years

 
The proportion of patients on dual antiplatelet therapy at 6 months (about 95%) and 1 year (about 89%) was also similar for the groups. By year 2 only 41% of the ISR group and 35.1% of the non-ISR group remained on dual therapy, although the vast majority still received aspirin (about 96% for both groups).

Multivariate analysis identified 3 predictors of TLF in the ISR group at 2 years:

• Prior CABG (OR 4.195; P < 0.001)
• Unstable angina (OR 2.516; P = 0.009)
• Age (OR 0.963; P = 0.021)

Overall, in-stent restenosis occurred almost 3 times more often in BMS than DES, but no differences were seen in any 2-year clinical endpoints between the different stent lesions. Interestingly, there were numerically more cases of definite/probable stent thrombosis in the BMS group than the DES group (6 vs. 1).

In a telephone interview with TCTMD, Sorin J. Brener, MD, of Weill Cornell Medical College (New York, NY), said the ZES results are quite similar to those of other DES and confirm current practice.

Moreover, he said he was unsurprised that Resolute, unlike older DES, performed as well in DES ISR as in BMS ISR. Like the authors, he attributed the finding largely to the fact that zotarolimus is a more potent antiproliferative agent than those employed in other DES.

Drug-Eluting Balloons a Promising Alternative

Although there has been a small resurgence in use of brachytherapy for treating in-stent restenosis, new-generation DES are the mainstay therapy in the United States, Dr. Brener said. On the other hand, he noted, “drug-eluting balloons represent an excellent solution,” especially for patients who already have a stent inside a stent. “We just don’t have them in the United States, but if I were practicing in Europe, I would start with a DEB 100% of the time.”

Bruno Scheller, MD, of the University of Saarland (Homburg, Germany), was skeptical of the implied superiority of ZES over drug-eluting balloons insofar as the latter appear to have not performed as well in DES in-stent restenosis. “It is risky to compare this supposed finding from a retrospective pooled analysis with the results of prospective randomized trials studying different patient populations with different devices,” he cautioned in an e-mail communication. For example, in the PEPCAD-DES trial, more than half of patients had repeated ISR before being treated with drug-eluting balloons and thus were at considerably higher risk, he noted. Furthermore, all of these patients underwent follow-up angiography at 6 months, whereas the majority of ISR patients in the current study did not.

Dr. Scheller pointed out that in contrast to the 2-year 2.5% stent thrombosis rate reported in the current study, thrombotic events after drug-eluting balloon treatment of ISR were only 0.2% over long-term follow-up in 5 randomized trials and 1 large registry despite dual antiplatelet therapy of only 1 to 3 months in most patients.

“The known benefits of drug-eluting balloons over DES in the treatment of ISR are the avoidance of another layer of metal and shortened dual antiplatelet therapy,” Dr. Scheller commented. Use of drug-eluting balloons in these difficult lesions is steadily increasing in Europe, especially in Germany, he said, and meanwhile the prospective, randomized RIBS IV and V trials are directly comparing a contemporary DES (Xience) with SeQuent Please (the gold standard in coronary drug-eluting balloons) in the treatment of both BMS and DES in-stent restenosis. First results are expected to be presented at TCT this fall, he added.

Study Details

Overall, ISR patients were older, not current smokers, and had more hypertension, hyperlipidemia, insulin-dependent diabetes, previous MI, and prior CABG. In addition, these patients more often underwent intervention for stable angina.

 

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Source:
Richardt G, Leschke M, Abdel-Wahab M, et al. Clinical outcomes of the Resolute zotarolimus-eluting stent in patients with in-stent restenosis: Two-year results from a pooled analysis. J Am Coll Cardiol Intv. 2013;Epub ahead of print.

 

 

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