PEPCAD-DES: Paclitaxel-Coated Balloon Bests Plain Balloon for DES Restenosis

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For revascularization of restenosis in a drug-eluting stent (DES), a paclitaxel-coated balloon is more effective in reducing late loss and early clinical events, particularly target lesion revascularization (TLR), compared with conventional balloon angioplasty.

The findings, which were first presented in November 2011 at the annual Transcatheter Cardiovascular Therapeutics scientific symposium in San Francisco, CA, were published online February 29, 2012, ahead of print in the Journal of the American College of Cardiology.

For the multicenter PEPCAD-DES trial, investigators led by Harald Rittger, MD, of Universitätsklinikum Erlangen (Erlangen, Germany), randomized 110 patients with DES restenosis in a 2:1 ratio to angioplasty with a paclitaxel-coated balloon (SeQuent Please, B. Braun, Melsungen, Germany; n = 72) or an uncoated balloon (n = 38).

After predilation, angioplasty was successful in all patients, although bailout stenting with a BMS was performed in 1 patient in each group. After PCI, acute gain, minimal lumen diameter (MLD), and percent diameter stenosis were similar between the treatment groups.

Angiographic Superiority

At 6-month angiographic follow-up (available in 86% of patients), late lumen loss at the target lesion, the primary endpoint, was lower with the paclitaxel-coated balloon compared with the uncoated balloon. Other angiographic endpoints including MLD, percent diameter stenosis, and binary restenosis also favored the drug-coated balloon (table 1).

Table 1. Angiographic Outcomes at 6 Months

 

Paclitaxel-Coated Balloon
(n = 64)

Uncoated Balloon
(n = 31)

P Value

Late Lumen Loss, mm
Target Lesion
Total Segment

0.43 ± 0.61
0.32 ± 0.55

1.03 ± 0.77
0.99 ± 0.44

< 0.001
< 0.001

MLD,  mm
Target Lesion
Total Segment

1.75 ± 0.70

1.65 ± 0.66

1.10 ± 0.73

1.00 ± 0.68

< 0.001

< 0.001

Diameter Stenosis
Target Lesion
Total Segment

29.6 ± 24.3%
32.3 ± 54.7%

51.1 ± 31.0%
54.7 ± 29.4%

< 0.001
< 0.001

Binary Restenosis
Target Lesion
Total Segment

17.2%
17.2%

58.1%
61.3%

< 0.001
< 0.001


Paclitaxel-coated balloons reduced late loss more than uncoated balloons in both nondiabetics (0.39 ± 0.54 mm vs. 0.91 ± 0.71 mm; P < 0.001) and diabetics (0.51 ± 0.72 mm vs. 1.45 ± 0.85 mm; P < 0.01). Moreover, paclitaxel-coated balloons showed a late loss advantage over uncovered balloons regardless of whether restenosis occurred in PES (0.46 ± 0.50 mm vs. 1.58 ± 1.03 mm; P = 0.021) or other DES types (0.41 ± 0.65 mm vs. 0.90 ± 0.65; P = 0.004).

 

Also at 6 months, the incidence of MACE (cardiac death, target-vessel MI, and TLR), driven mainly by reduced TLR, was lower in the paclitaxel balloon group compared with the uncoated-balloon group. Rates of cardiac death also were lower with coated balloons, while no difference was seen for MI. There were no cases of definite stent thrombosis (table 2).

 Table 2. Clinical Outcomes at 6 Months

 

Paclitaxel-Coated Balloon
(n = 72)

Uncoated Balloon
(n = 38)

P Value

TLR

15.3%

36.8%

0.005

MI

0

2.6%

0.35

Cardiac Death

1.4%

10.5%

0.048

MACE

16.7%

50.0%

< 0.001

Definite Stent Thrombosis

0

0

­

 

The authors observe that rates of late lumen loss and TLR seen with paclitaxel-coated balloons in the current trial are “in the same range” as those achieved with DES in the ISAR-DESIRE 2 study (Mehilli J, et al. J Am Coll Cardiol. 2010;55:2710-2716).

Dr. Rittger and colleagues conclude that “although use of DES for DES restenosis is a common treatment strategy, the use of a [paclitaxel-coated balloon] should be considered as an effective treatment strategy for DES restenosis after successful balloon predilation.”

According to Juan F. Granada, MD, of the CRF Skirball Research Center (Orangeburg, NY), the pathophysiology of in-stent restenosis differs markedly between BMS and DES. In a telephone interview with TCTMD, he said BMS lesions typically consist of quiescent scar tissue, and drug-coated balloons have proven very effective in opening them—in some studies even showing negative late loss. “[On the other hand,] this is one of the first papers to address the question of whether drug-coated balloons are as effective for treating [more active] DES restenosis,” he added.

Not ‘Real-World’ Restenoses

But, Dr. Granada noted, a major limitation of PEPCAD-DES is that most of the restenoses treated were low risk—short, focal lesions in patients with stable angina—and thus not representative of patients in the ‘real world.’ “In interventional cardiology today, the technologies and techniques tend to be complex, and they lead to in-stent restenoses that are complex as well—we’re talking about bifurcation lesions, left main lesions, stenting after CTO recanalization,” he said.

“So these results are encouraging, but they don’t demonstrate the efficacy of this technology in long or diffuse in-stent lesions,” he concluded.

However, in an email communication with TCTMD, Bruno Scheller, MD, of the University of Saarland (Homburg, Germany), noted that “53.6% of the treated lesions were at least the second restenotic lesion, identifying a high-risk patient population despite the relatively short lesion lengths.”

Drug-Coated Balloons vs. DES?

Even so, “what we still don’t know is whether a drug-coated balloon is going to be able to outperform DES” in the real world, Dr. Granada said.

But in theory, use of a drug-coated balloon instead of a second DES for in-stent restenosis—thereby avoiding another layer of metal and polymer—“makes a lot of sense,” he  added. “We know that the pharmacokinetic profile of drug-coated balloons allows them to achieve long-term tissue levels of drug. Now we need to demonstrate in a large clinical trial that [this strategy] is better than DES for DES restenosis.”

Dr. Scheller noted other advantages of drug-coated balloons over DES, such as homogeneous drug delivery to the vessel wall, preservation of the artery anatomy, and the potential for repeated use if restenosis recurs.

Agreeing that the theoretical superiority of drug-coated balloons needs confirmation in randomized trials, he pointed to the ongoing ISAR DESIRE III study, which is comparing 3 different modalities for treating restenosis in limus-eluting stents: the SeQuent Please balloon, conventional balloon angioplasty, and a paclitaxel-eluting stent.

Currently, 5 drug-coated balloons are approved for clinical use in Europe, Dr. Scheller observed, although so far most positive clinical evidence for this category comes from randomized trials of SeQuent Please.

Study Details

Clinical and angiographic characteristics did not differ between the 2 groups, except that patients who received drug-coated balloons were older (69.8 ± 10.8 years vs. 64.0 ± 11.3 years; P = 0.02). DES lesions were the first restenosis in 46.4% of cases and at least the second in 53.6%.

Before the procedure, mean reference vessel diameter was about 2.3 mm, while mean lesion length was about 12 mm. Dual antiplatelet therapy was prescribed for 6 months for all patients.

 


Source:
Rittger H, Brachmann J, Sinha A-M, et al. A randomized, multicenter, single-blinded trial comparing paclitaxel-coated balloon angioplasty with plain balloon angioplasty in drug-eluting stent restenosis: The PEPCAD-DES study. J Am Coll Cardiol. 2012;Epub ahead of print.

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Disclosures
  • Dr. Rittger reports receiving speaker honoraria from B. Braun and Siemens.
  • Dr. Granada reports serving as a consultant for Medrad; in addition, the CRF Skirball Research Center receives grant support from multiple drug-eluting balloon makers.
  • Dr. Scheller reports receiving grant support from B. Braun; receiving speaker honoraria from B. Braun and Invatec; serving as a major stock shareholder/equity in InnoRa GmbH; and holding intellectual property rights as co-inventor of a patent application submitted by Charité University Hospital (Berlin, Germany).

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