Drug-Eluting Balloon Continues to Show Positive Results in SFA, Popliteal Disease

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On the heels of research demonstrating impressive results in long, below-the-knee lesions, a paclitaxel-eluting balloon has demonstrated reduced late lumen loss and adverse events at 6 months compared with standard balloon angioplasty in femoropopliteal disease. Findings from the small, randomized trial were presented Monday, September 12, 2011, at the annual meeting of the Cardiovascular and Interventional Radiological Society of Europe Congress in Munich, Germany.

For the PACIFIER (Paclitaxel-coated Balloons in Femoral Indication to Defeat Restenosis) trial, researchers led by Michael Werk, MD, of Martin-Luther-Hospital (Berlin, Germany), randomized 91 patients with SFA and popliteal disease at 3 German centers to treatment with standard balloon angioplasty (n = 47) or the In.Pact Pacific drug-eluting balloon (n = 44; Medtronic, Minneapolis, MN). The In.Pact balloon is coated with a proprietary formulation of paclitaxel and urea, which serves as a hydrophilic spacer to facilitate separation and release of paclitaxel into the vessel wall.

In the trial, the majority of the patients were Rutherford stage 3, with an average lesion length of about 7 cm. In-stent restenosis represented 16% of the lesions treated in the drug-eluting balloon group and 13% in controls.

Successful guidewire crossing was achieved in 100% of patients in both groups, and rates of provisional stenting, in the case of flow-limiting dissection or persistent residual stenosis, were also similar (21% in the drug-eluting balloon group vs. 34% in controls; P = 0.17).

At 6 months, there were 2 deaths (both in the control group) and 1 bypass surgery a week following intervention in the drug-eluting balloon group. Overall, 9 patients were lost to follow-up. The primary endpoint of late lumen loss was significantly improved in drug-eluting balloon patients on 6-month angiography, as were other angiographic endpoints (table 1).

Table 1. Six-Month Angiographic Outcomes

Abbreviation: MLD, minimum lumen diameter.

Late lumen loss also favored the paclitaxel-eluting balloon group in the subset of patients treated for in-stent restenosis (-0.4 mm vs. 1.2 mm in controls). In addition, the drug-eluting balloon lowered the predefined composite of adverse events (TLR, amputation, mortality) at 6 months, driven primarily by a reduction in TLR (table 2).

Table 2. Six-Month Clinical Outcomes

In an e-mail communication with TCTMD, Dr. Werk noted that PACIFIER follows previous randomized trials such as Thunder and FemPac that have shown positive results with a paclitaxel-coated balloon. “We expected the coated balloon to perform better than the standard PTA-catheter,” he said. “Our results are surprising in that the late lumen loss is not just significantly better than in the control group, but independent review confirmed a value of -0.05 mm. This is the first peripheral study showing an impact we have so far only seen in cardiac trials.”

Prior to the current results, researchers led by Andrej Schmidt, MD, of the Center of Vascular Medicine, Angiology, and Vascular Surgery (Leipzig, Germany), showed superior midterm restenosis and repeat revascularization rates with the In.Pact balloon compared with historical controls in claudicant patients with long-segment below-the-knee lesions. Their results appeared in the September 6, 2011, issue of the Journal of the American College of Cardiology.

Recent Trials Differ in Key Ways

Dr. Werk noted some important differences between the PACIFIER trial and the study by Schmidt et al, which involved infrapopliteal disease with much longer lesion lengths (about 17 cm). “We treated femoropopliteal arteries. The comorbidity is much higher in patients with infrapopliteal disease [because] the nature of infrapopliteal atherosclerosis is different,” he explained. “In femoropopliteal arteries we expect that the highest benefit for patients may occur when usage of a paclitaxel coated balloon can make a stent placement non-essential to prevent restenosis. This is important in vessel segments that underlie high bending and twisting forces in the hip and knee region.”

In a telephone interview with TCTMD, Michael R. Jaff, DO, of the Massachusetts General Hospital (Boston, MA), agreed that while PACIFIER and the JACC paper used the same balloon in patients with peripheral disease, the trials were very different due to the location and lengths of lesions involved. He also was critical of the provisional stenting rate in PACIFIER. “One-fifth of the patients in the drug-eluting balloon arm, and one-third of the patients in the PTA arm received provisional stenting,” he said. “I don’t think that’s low, and I certainly don’t think these were complex, long lesions like in the Schmidt trial.”

Nevertheless, “I think this is a nice supportive study,” Dr. Jaff said. “The results continue to show a consistent preservation of patency in the short term with a drug coated balloon over a bare balloon.”

Reason for Recent Trend: Better Manufacturing

He pointed to a simple reason for the recent trend of positive results with drug-eluting balloons. “A clear explanation is that the manufacturers have gotten better at coating the balloon with a consistent amount of drug and excipient, transfecting the drug across the endothelium, and minimizing distal embolization,” Dr. Jaff said. “They’ve just gotten better at making them.”

He agreed with Dr. Werk regarding the kinds of lesions such devices will be most useful for. “I think drug-coated balloons are going to replace bare balloons in SFA lesions, which is what this study suggests,” Dr. Jaff said. “I don’t think they’re going to have an impact on 20-plus centimeter SFA lesions, so I don’t think stents are done. The only shocker to all of this was the Schmidt paper, because they had long lesions in the sickest patients.”

According to Dr. Werk, a key question is how drug-eluting balloons stack up against stents. “Adequate studies to find the answer to this are as yet missing,” he said.

Regardless, Dr. Jaff does not expect drug-eluting balloons to arrive on the US market for some time. “In the United States, I can’t imagine seeing one of these devices through the regulatory and reimbursement process for sale before 2015,” he predicted. “And that’ll be if every T is perfectly crossed and every I is dotted. So I think we’ve got a long way to go before these hit the market here.”

 

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Source:
Werk M. The Pacifier trial: A randomized multicenter trial evaluating prevention of restenosis with paclitaxel-coated PTA balloon catheters in stenosis or occlusion of femoropopliteal arteries [first report]. Presented at: Cardiovascular and Interventional Radiological Society of Europe Congress; September 12, 2011; Munich, Germany.

 

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