Complications of In-Stent Restenosis High, Traditional Risk Factors Absent

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Recurrence of in-stent restenosis (ISR) after first-generation drug-eluting stent (DES) implantation is not an infrequent problem, and optimal therapy remains unclear and challenging, according to a new study published online February 13, 2012, ahead of print in Circulation: Cardiovascular Interventions.

Ron Waksman, MD, of Washington Hospital Center (Washington, DC), and colleagues analyzed data on 563 patients from their institution presenting with recurrent symptoms and/or ischemia after DES implantation and angiographic evidence of in-stent restenosis from May 2003 to September 2008. Patients were treated with either repeat DES (n = 327), vascular brachytherapy (n = 132), or conventional balloon angioplasty (n = 104).

Different Therapies, Same Outcomes

The 3 treatment groups had similar baseline characteristics, with the exception of higher hypertension rates in the repeat DES group and a greater frequency of prior CABG in the brachytherapy group.

The overall incidence of recurrent DES failure or clinically driven TLR at 1-year (the primary endpoint) was similar among the 3 groups. All other outcomes were also equivalent at 1 year (table 1).

Table 1. Clinical Outcomes at 1-Year

After univariate and multivariate analysis, there were no factors associated with the occurrence of TLR at 1 year.

Indications for the failed DES implantations were significantly different among the 3 groups. De novo lesions were more common in patients treated with repeat DES, whereas in-stent restenosis in BMS was more frequent in patients treated with balloon angioplasty, and DES ISR and brachytherapy failure were more common in patients treated with brachytherapy. The mean stent diameter (2.98 ± 0.53 mm) and the mean total stent length (26.8 ± 13.3 mm) were similar among the 3 groups.

In a subgroup analysis, patients with diffuse/proliferative ISR were more likely than those without diffuse/proliferative ISR to receive a greater number of stents (1.3 ± 0.6 vs. 1.2 ± 0.4; P = 0.005) and longer stents (30.6 ± 16.8 mm vs. 25.9 ± 12.2 mm; P = 0.005). This group also was more frequently treated with brachytherapy (34.5% vs. 20.3%; P < 0.001).

‘Disconcerting’ Results

In a telephone interview with TCTMD, Roxana Mehran, MD, of Mount Sinai Medical Center (New York, NY), said the death rate of the overall population was “disconcerting” and the rate of TLR observed was “very high.”

“Previous studies have shown that because DES restenosis is a focal restenosis, usually with a recurrent DES we don’t have the [ISR] recurrence as high as this,” she said, adding that in second-generation stents, recurrence rates are closer to 10%.

Because the patients studied represent such a high-risk group, the authors write that “this population’s characteristics are likely responsible for the high rates of observed repeat TLR and MACE.” They add that “regardless of the treatment modality used, the rate of cardiovascular events and TLR in such a complex population is expected to be high.”

Still, Dr. Mehran said she would have liked to see more detail on the types of ISR treated in this study.

“Most of the patients had sirolimus as their failed stent type, the stent lengths were not that long, and we don’t know how much of [these patients had] IVUS-guided procedures,” she said. “The other very interesting piece is that most of these patients actually had a focal restenosis [(50.2%)] and … a good number of their patients [overall] had some IVUS guidance [(57.0%)]. So you would have expected a much better outcome than what was seen.”

‘Not a Benign Problem’

Dr. Mehran also commented on the large number of patients treated with vascular brachytherapy in the study. “I think most of those patients had some diffuse pattern of in-stent restenosis, which is why they were treated with vascular brachytherapy,” she said. “But this is a very large population of patients and it’s a little bit humbling to see that this is not a benign problem. It’s really not going away.”

The authors note that the brachytherapy subgroup failed fastest after the initial procedure, “suggesting that patients selected for [vascular brachytherapy] had a more aggressive neointimal proliferative response to the initially placed DES.” They add that these results support the use of this treatment as a “reasonable, safe, and effective method” for DES in-stent restenosis, but that it “does not seem to be superior to other alternatives.”

Going forward, Dr. Mehran said that because the stents used in this study were all first-generation and have since been replaced by “much better and safer” everolimus-eluting stents, she would like to see the same follow-up done with these patients implanted with second-generation DES.

The authors add that they would also like to see the role of drug-eluting balloons further evaluated for treatment of these patients.

Study Details

At the initial procedure, patients received either sirolimus- (81.8) or paclitaxel-eluting stents (17.7). For repeat DES, sirolimus-, paclitaxel-, zotarolimus- or everolimus-eluting stents were used at the operator’s discretion.

For all patients, the prevalence of comorbidities was high and included:

• Hyperlipidemia (95.0%)
• Hypertension (93.4%)
• Diabetes (43.7%)
• Previous MI (45.8%)
• Prior CABG (39.2%)

 

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Source:
Maluenda G, Ben-Dor I, Gaglia MA, et al. Clinical outcomes and treatment after drug-eluting stent failure: The absence of traditional risk factors for in-stent restenosis. Circ Cardiovasc Interv. 2012;Epub ahead of print.

 

 

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