Drug-Eluting Balloons Show ‘Impressive’ Results in Below-the-Knee Lesions

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Drug-eluting balloons can achieve superior midterm restenosis and repeat revascularization rates compared with historical controls in patients with long-segment below-the-knee lesions, according to results of a single-center patient series published in the September 6, 2011, issue of the Journal of the American College of Cardiology.

Researchers led by Andrej Schmidt, MD, of the Center of Vascular Medicine, Angiology, and Vascular Surgery (Leipzig, Germany), used the In.Pact Amphirion paclitaxel-eluting balloon (Medtronic, Minneapolis, MN) to treat 104 patients (109 limbs) at their institution with either critical limb ischemia (82.6%) or severe claudication (17.4%). Prior to treatment, over three-fourths of patients (77.1%) had complete or functional occlusion of all 3 infrapopliteal lesions, with a mean lesion length of 176 ± 88 mm. More than a single artery was treated in only 5 limbs.

The In.Pact balloon is coated with a proprietary formulation of 3.0 µg paclitaxel/mm² and urea, which serves as a hydrophilic spacer to facilitate separation and release of paclitaxel into the vessel wall. In the study, drug-eluting balloons had a diameter of 2.0 to 4.0 mm and a length of 80 to 120 mm. Predilation with an uncoated balloon was performed in all cases.

Clinical Improvement, Complete Wound Healing Seen

Patients received a mean of 1.9 drug-eluting balloons per artery. Interventional success was achieved in all limbs, with stenting required in 5 cases. Peri-interventional toe amputation was necessary in 3 patients. One patient died as a result of a major amputation performed 21 days after angioplasty.

At 3 months, there were 8 additional deaths and 1 patient lost to follow-up. In the remaining 94 patients, clinical improvement was seen in 75.8% of treated limbs, with 22.2% unchanged and 2.0% clinically worse. There were 3 additional toe amputations. Complete wound healing was noted in 41.9% of the limbs classified as Rutherford-Becker category 5.

On 3-month angiography in 74 patients (79 treated limbs, 84 treated arteries), restenosis greater than 50% was found in 27.4% of arteries, with an occlusion rate of 8.3%. The researchers noted that by comparison, in a similar patient cohort treated with standard balloon angioplasty, the same group of investigators achieved a restenosis rate of 69% at 3 months, representing a 61% relative reduction with the newer device.

In over half of the restenosed arteries (61%) in the current trial, the pattern of restenosis was focal (< 20% of the length of the initial target lesion). Restenosis or reocclusion of the entire target lesion occurred only in 8 arteries (9.5%). Higher restenosis rates were seen after treatment of distal segments, especially when foot arteries were involved.

High Limb Salvage, Low TLR Achieved

After a mean follow-up of roughly 1 year (378 days), clinical improvement was noted in 91.2% of treated limbs, with no bypass surgeries performed during the entire study period. The TLR rate was 17.3%, which compares favorably to the rate of 50% achieved in the researchers’ previous series using standard angioplasty (relative reduction of 65.4%). In the current trial, limb salvage was achieved in almost all patients with chronic limb ischemia (CLI; 95.6%). In addition, complete wound healing occurred in 74.2% of patients with Rutherford-Becker category 5 limbs at baseline. The 1-year mortality rate was 16.3%, encompassing 8 additional deaths for unrelated reasons. There were 4 unplanned amputations during this period.

The shift in Rutherford-Becker category was drastic. There were roughly 70 category 5 limbs at baseline, and 19 category 4 and 3 limbs each. At 12.5 months, there were roughly 61 category 0 limbs, with 6, 5, 7, 2, and 10 limbs, respectively, in categories 1, 2, 3, 4, and 5.

The researchers found the use of drug-eluting balloons to be safe in below-the-knee lesions, with an acceptable amputation rate in patients with CLI. Reducing TLR is where drug-eluting balloons have the most potential to improve clinical outcomes compared with standard balloons, they note, adding that hopefully the cost reduction in TLR procedures avoided will balance the extra expense of the newer devices.

“This first report of the use of [drug-eluting balloons below the knee] suggests that they are safe and effective in this arterial region,” the authors conclude. “In addition, if restenosis occurred, it was associated with a favorable, focal pattern. The 1-year clinical results are promising and seem to confer a durable benefit.”

Results ‘Impressive,’ But Cost, Mortality Concerning

In an accompanying editorial, Michael R. Jaff, DO, of the Massachusetts General Hospital (Boston, MA), notes, “The authors demonstrated, for the first time, impressive results of endovascular intervention using an angioplasty balloon coated with paclitaxel and a novel spacer, urea. Although there have been preliminary reports of the efficacy of drug-coated balloons in PAD, this particular study demonstrated impressive results with much longer anatomic lesions in the most challenging of arterial beds, the infrapopliteal arteries.”

However, Dr. Jaff points out limitations of the study such as its nonrandomized single-center nature and potential for selection bias. In addition, while a formal cost analysis will be required to determine the advantages of drug-eluting balloons vs. standard angioplasty with uncoated balloons, “one must question whether costs will favor [the newer] technology in the era of healthcare reform,” he cautions.

Dr. Jaff’s biggest concern, though, was the 16.3% mortality rate at 1 year, which he notes is “significantly higher” than that for women with breast cancer. “For any endovascular technology to represent a true breakthrough, not only must the treatment promote improvement in functional capacity and limb salvage, but also strategies to prolong overall survival must be even more effective,” he stresses. “Without the latter, the relevance of patent limb arteries wanes.”

In an e-mail communication with TCTMD, Bruno Scheller, MD, of the University of Saarland (Homburg, Germany), called the results with the In.Pact balloon “remarkable,” especially compared with the authors’ previous experience with uncoated balloons in similar patients.

Restenosis Rates Key, Deaths Not the Point

Dr. Scheller cautioned, though, that as with DES, not all drug-coated balloons are alike, and the current results in no way represent a class effect. Furthermore, “the excellent results of the study by Schmidt et al have to be evaluated in randomized clinical trials comparing drug-coated balloons with conventional angioplasty, bare-metal stents, and finally drug-eluting stents,” he said.

Dr. Scheller added that for shorter infrapopliteal lesions, both DES and drug-eluting balloons may become viable alternatives. But “for longer diffusely diseased lesions representing the majority of infrapopliteal disease, a non-stent based approach of local drug delivery may become the better alternative,” he said.

Regarding the mortality rate, Dr. Scheller cautioned that a local infrapopliteal treatment modality cannot be expected to reduce deaths in a systemic disease like atherosclerosis affecting multiple vascular territories. However, “the reduction of restenosis rates in such complex disease will improve life quality,” he said. The crucial question that remains to be proved in randomized trials, he observed, is if such treatment will result in improved limb salvage.

Sources:

1. Schmidt A, Piorkowski M, Werner M, et al. First experience with drug-eluting balloons in infrapopliteal arteries. Restenosis rate and clinical outcome. J Am Coll Cardiol. 2011;58:1105-1109.
2. Jaff MR. The breakthrough balloon for critical limb ischemia? J Am Coll Cardiol. 2011;58:1110-1111.

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