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When restenosis develops in femoropopliteal stents, the odds of recurrence after revascularization with balloon angioplasty depend largely on the type of lesion treated and the reference vessel diameter, according to a study published in the January 3, 2012, issue of the Journal of the American College of Cardiology. According to the authors, occlusive lesions are not only more prone to repeat restenosis, they are more challenging to treat.

Investigators, led by Atsushi Tosaka, MD, of Kokura Memorial Hospital (Kitakyushu, Japan), looked at 133 cases of in-stent restenosis in 116 patients who had been enrolled in a multicenter, retrospective, observational study of femoropopliteal lesions treated with BMS. All cases of restenosis were treated with balloon angioplasty.

Types of In-Stent Restenosis Parsed

In-stent lesions were categorized into 3 angiographic patterns:

• Class I, or focal lesions (≤ 50 mm in length), which accounted for 29% of in-stent restenoses
• Class II, or diffuse lesions (> 50 mm in length), which accounted for 38%
• Class III, or totally occluded lesions, which accounted for 33%

Over a mean follow-up of 24 ± 17 months, in-stent restenosis recurred at a rate of 49.9% in class I lesions, 53.3% in class II lesions, and 84.8% in class III lesions, while the respective rates of recurrence of total occlusions were 15.9%, 18.9%, and 64.6%.

Over 2 years, class III lesions (occlusive) were less likely to remain free from recurrence than either class I or class II lesions or class I and class II lesions combined (the restenotic group):

• Class III vs. class I: 15.2% vs. 50.1% for in-stent restenosis and 35.4% vs. 84.1% for occlusion (both P < 0.0001)
•  Class III vs. class II: 15.2% vs. 46.7% for in-stent restenosis (P = 0.0003) and 35.4% vs. 81.1% for occlusion (P < 0.0001)
• Class III vs. classes I and II: 15.2% vs. 48.0% for in-stent restenosis and 35.4% vs. 82.4% for occlusion (both P < 0.0001)

All-cause death occurred in 14 patients, bypass surgery was performed on 11 limbs, and major amputation was performed on 1 limb during follow-up. Although the differences in survival among the classes were not significant, bypass surgery rates increased with the classes (class I vs. class II, P = 0.0077; class II vs. class III; P = 0.0025; stenosis group vs. class III; P = 0.0001).

Predictors of Recurrence 

In multivariate analysis, in-stent restenosis class III and reference vessel diameter were independent predictors of both recurrent in-stent restenosis and recurrent occlusion (table 1).

Table 1. Multivariate Predictors of Recurrent In-Stent Restenosis, Occlusion

 
In an accompanying editorial, John R. Laird Jr, MD, of the University of California, Davis Medical Center (Sacramento, CA), and Khung Keong Yeo, MD, of the National Heart Centre (Singapore), note that “[f]emoropopliteal in-stent restenosis remains one of the most frustrating problems for the endovascular specialist,” occurring in 18% to 40% of patients within the first year of stenting. Restenosis is more common after stenting of longer lesions (> 15 cm) and may occur in connection with stent fracture, they add.

Balloon Angioplasty No Longer Standard Therapy

Drs. Laird and Yeo point out that the relevance of the current findings to contemporary practice is limited by the fact that only balloon angioplasty was used to treat in-stent restenosis. In many countries outside the United States, the availability of drug-eluting balloons and stents has changed the paradigm for the treatment of femoropopliteal in-stent restenosis, they say, while in the United States, treatment includes debulking therapies, cutting or scoring balloons, repeat stenting, or the use of self-expanding stent grafts.

The editorial also questions the clinical usefulness of the classification system the study authors employed, especially insofar as it implies that all nonocclusive restenoses (classes I and II) can be treated by balloon angioplasty with equal efficacy regardless of their length. That “does not reflect clinical reality,” Drs. Laird and Yeo write, adding that the choice of a 50 mm cutoff to separate focal and diffuse lesions is “not optimal for a vascular bed in which long segment stenting (> 200 mm stented length) is common.”

The editorialists note that drug-eluting balloons, which have already proven effective for femoropopliteal disease, “hold promise for the treatment of femoropopliteal [in-stent restenosis].” Meanwhile, the largest experience with drug-eluting technology for this indication comes from the ‘real-world’ Zilver PTX multicenter registry of cases involving the paclitaxel-eluting Zilver stent (Cook Medical, Bloomingdale, IN), which includes 142 in-stent lesions. In this subset, freedom from TLR at 12 and 24 months was 78% and 69%, respectively.

Study Details

About two-thirds of patients were male and three-quarters had diabetes; about one-quarter were undergoing hemodialysis.

For initial treatment, all patients received 1 of 2 nitinol BMS: the Luminexx stent (Bard, Murray Hill, NJ) or the S.M.A.R.T. stent (Cordis/J&J, Miami, FL).

All patients had received dual antiplatelet therapy (aspirin 100 mg/day plus clopidogrel 75 mg/day or ticlopidine 200 mg/day) for more than 2 days before balloon angioplasty. In addition, unfractionated heparin was injected intra-arterially before the intervention at a dose of 3,000 to 5,000 IU. After the procedure, all patients were prescribed lifelong aspirin (100 mg/day).

2. Laird JR, Yeo KK. The treatment of femoropopliteal in-stent restenosis: Back to the future. J Am Coll Cardiol. 2012;59:24-25.

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