PACIFIER Published: Drug-Eluting Balloon Helps Treat Femoropopliteal Lesions


In patients undergoing angioplasty for femoropopliteal disease, use of a paclitaxel-eluting rather than an uncoated balloon can reduce late lumen loss and restenosis at 6 months and lessen the need for repeat treatment at 1 year. The findings, from a small randomized trial, were published online November 27, 2012, ahead of print in Circulation: Cardiovascular Interventions.

Data from the PACIFIER (Paclitaxel-coated Balloons in Femoral Indication to Defeat Restenosis) trial were previously presented in September 2011 at the Cardiovascular and Interventional Radiological Society of Europe Congress in Munich, Germany.

For the study, researchers led by Michael Werk, MD, of Martin-Luther-Hospital (Berlin, Germany), randomized 85 patients with symptomatic femoro-popliteal disease at 3 German centers to angioplasty with the In.Pact Pacific drug-eluting balloon (DEB; n = 44; Medtronic, Minneapolis, MN) or an uncoated Pacific Xtreme balloon with the same platform (n = 47; Medtronic). Six patients were treated twice, resulting in a total of 91 procedures.

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.

Angiographic Results Translate into Clinical Edge

Procedural success, defined as residual diameter stenosis ≤ 30% in the absence of periprocedural complications, was achieved in 100% of cases.

At 6 months, quantitative angiography in 69 cases with available follow-up showed that DEB treatment reduced both late lumen loss (primary endpoint) and the rate of binary restenosis compared with uncoated balloons (table 1).

Table 1. Angiographic Outcomes at 6 Months

 

DEB
(n = 35)

Uncoated Balloon
(n = 34)

P Value

Late Lumen Loss, mm

-0.01

0.65

0.001

Binary Restenosis

8.6%

32.4%

0.01


By 12 months, 2 patients had died from cardiovascular failure and a third from pneumonia and septic shock; all were in the uncoated balloon group. DEB-treated patients experienced fewer major adverse events (death, target limb amputation, or TLR), driven by a reduction in TLR (table 2).

Table 2. Clinical Outcomes at 12 Months

 

DEB
(n = 44)

Uncoated Balloon
(n = 47)

P Value

Major Adverse Events

7.1%

34.9%

0.003

Amputation

0

0

> 0.99

Death

0

6.9%

0.24

TLR

7.1%

27.9%

0.02


DEB therapy provided superior protection against late lumen loss across lesion subtypes: de novo vs. restenotic, nonocclusive vs. occlusive, and short vs. long. DEB-treated lesions with higher postprocedural residual stenosis were likely to have lower late lumen loss, while some even experienced late lumen gain, a sign of plaque regression.

Among the 35 female patients, the differences in 6-month late lumen loss and 12-month TLR numerically favored drug-coated balloons but did not reach statistical significance.

Numerous Trials, Coatings in DEB Field

In an e-mail communication with TCTMD, Dr. Werk conveyed that PACIFIER does not stand alone.

“The first clinical studies testing paclitaxel-coated balloons in the SFA started in 2006 and were published in 2008. Now, in 2012, we are looking at 4 randomized controlled trials—THUNDER, FemPac, PACIFIER, and LEVANT I—showing the superiority of DEB against uncoated balloon angioplasty. I consider this to be a significant clinical impact for a relatively new method,” he said, noting that clinical studies of drug-coated balloons vs. BMS and DES are “eagerly awaited.”

Preclinical studies indicate that different coatings have different characteristics, Dr. Werk observed, adding that because no clinical trials have pitted various DEB types against each other, it is unknown how these might translate into performance.

In an e-mail communication, Bruno Scheller, MD, of the University of Saarland (Homburg, Germany), told TCTMD that the “paclitaxel-urea coating [of the In.PACT Pacific balloon used in PACIFIER] shows strong similarities to the original Paccocath coating in terms of reduction of neointimal formation and tissue kinetics in the animal model. These coatings with biocompatible additives (iopromide or urea) may represent the currently best available technology.” He reported that trials looking at coatings that involve polysorbate or detergents as additives will soon be published.

Selecting the Best Candidates

The PACIFIER finding that patients with the highest plaque burden stood to gain the most from DEB treatment is interesting, Dr. Scheller commented, in that it “questions the paradigm of an optimal primary result after angioplasty. Furthermore, it may indicate vascular restoration with plaque regression after [drug-coated balloon] treatment.”

Dr. Werk suggested that a possible explanation for the positive remodeling is that “more trauma at the moment of [angioplasty] may allow the drug to penetrate endothelial cells more easily.”

He advised that, based on current knowledge, the best candidates for DEB treatment are lesions with mild to moderate calcification, unsuitable anatomy for stenting, in-stent restenosis, or focal disease. The lack of significant benefit from DEB treatment in women, Dr. Werk said, “may well be due to sample size.”

According to Dr. Scheller, subgroup analyses of PACIFIER and other trials “indicate antirestenotic efficacy independent of the lesion type.”

Study Details

Baseline patient, lesion, and procedural factors were well balanced between groups. The number of devices per case in the DEB group was significantly higher than in the control group, however, due to the fact that a DEB can only be used once, so longer lesions required more than 1 balloon.

 


Source:
Werk M, Albrecht T, Meyer D-R, et al. Paclitaxel-coated balloons reduce restenosis after femoro-popliteal angioplasty: Evidence from the randomized PACIFIER trial. Circ Cardiovasc Interv. 2012;Epub ahead of print.

 

 

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Disclosures
  • The study was supported by an unrestricted grant from Medtronic.
  • Dr. Werk reports having lectured for and received research grants from Medtronic.
  • Dr. Scheller reports serving as a shareholder of InnoRa GmbH (Berlin, Germany), a company responsible for the preclinical and first clinical studies of this specific DEB.

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