Paclitaxel-Coated Balloon Cuts Late Lumen Loss After PCI for In-Stent Restenosis

Steve Stiles

April 04, 2008

April 4, 2008 (Chicago, IL) - It's not your father's angioplasty balloon, it's a delivery system for antiproliferative drugs that may have some advantages over drug-eluting stents (DES) in some kinds of PCI.

Treatment of in-stent restenosis (ISR) using a balloon coated from end to end with paclitaxel achieved better six-month angiographic results, at least by some measures, than stenting with the widely used Taxus (Boston Scientific) in a small randomized pilot trial [1].

In the Paclitaxel-Eluting PTCA-Balloon Catheter in Coronary Artery Disease-2 In-Stent Restenosis (PEPCAD-2 ISR) trial, the clearest superior outcome for the drug-coated balloon was in its primary end point, lumen loss six months after the procedure. Such late lumen loss was cut by about half (p=0.02) after ISR treatment with the SeQuent-Please balloon catheter (B Braun Melsungen AG) compared with the paclitaxel-coated Taxus stent. However, also in the primary analysis based on intention to treat (ITT), the binary restenosis rate wasn't significantly lower with the investigational balloon catheter.

The findings were reported here this week by Dr Martin Unverdorben (University of Frankfurt, Frankfurt am Main, Germany) at the American College of Cardiology Scientific Sessions/i2 Summit-SCAI Annual Meeting.

Unverdorben also presented the results based on how patients were actually treated once the study was under way; sometimes the ISR lesion couldn't be crossed with a stent, prompting crossover to balloon angioplasty, and a few patients randomized to receive the coated balloon had lesions that ultimately required stents. Results with the coated balloon looked better in this "as-treated" analysis, he said, with a significantly decreased binary restenosis rate and superior six-month rates of target lesion revascularization (TLR) and major adverse cardiac events (MACE).

Event-free survival rates were numerically but nonsignificantly higher at both six and 12 months after coated-balloon intervention in the ITT analysis; the differences edged wider to become significant at both time points in the as-treated analysis, Unverdorben explained.

According to the featured discussant for the PEPCAD-2 ISR presentation, Dr Steven R Bailey (University of Texas Health Sciences Center, San Antonio), the six-month late lumen loss of 0.20 mm--in contrast to the 0.45-mm loss in the Taxus group--"is remarkably low . . . and certainly suggests that the conclusions are appropriate." He pointed out, however, that there were no clinical differences in the more important prospectively defined ITT analysis and cautioned that the study was small, with only 131 patients. And, he said, there are lots of unknowns about the uptake of paclitaxel as delivered by the balloon, as well as suggestions in the data that Taxus stenting may have been performed suboptimally, potentially biasing outcomes in favor of the balloon.

On the other hand, as described by Unverdorben for heartwire , one of the coated balloon's most important differences from the DES in treating ISR is the obvious one: after dilatation, no additional stent is left behind. Also, he added, the paclitaxel coating extends the entire length of the SeQuent balloon and is applied more or less evenly to the arterial wall.

In contrast, DES coatings are limited to the length of the stent itself and apply the drug unevenly, with concentrations highest where the stent struts make contact with the artery, according to Unverdorben; tissue uptake of the drug is therefore inconsistent across the vessel wall. And unlike a DES, he said, the coated balloon does not use a polymer matrix to convey paclitaxel; the drug is bound to the balloon at a concentration of 3 µg/mm2 using the low-osmolar contrast agent iopromide as an adhesive. DESpolymers are suspected of being inflammatory, he observed.

"Right now, our data show that the [paclitaxel-coated] balloon is superior to [Taxus] stenting in in-stent restenosis," he told heartwire . "If future results confirm it, this balloon has clear advantages over stenting. It's potentially cheaper and is associated with a shorter [duration of] clopidogrel therapy, which would increase safety."

Angiographic and clinical outcomes in PEPCAD-2 ISR, by method of analysis and treatment group
End point Paclitaxel-coated balloon Taxus stent p
Intention-to-treat analysis n=66 n=65
Late lumen loss* (mm) 0.20 0.45 0.02
Binary in-segment restenosis (%) 7 20 0.06
TLR (%) 6.3 15.4 0.10
MACE (%) 7.8 16.9 0.20
"As-treated" analysis n=66 n=60
Late lumen loss (mm) 0.19 0.47 0.03
Binary in-segment restenosis (%) 3.4 20.4 0.007
TLR (%) 3.1 16.7 0.02
MACE (%) 4.7 18.3 0.02
*Primary end point

For the study, 131 patients with stenoses <22 mm in length within bare-metal stents in native coronaries were randomized to treatment with the coated balloon or the Taxus; patients could have stable or unstable angina, but any with MIs were excluded. The two groups didn't differ significantly in the coronary distribution of target lesions, number of diseased vessels, mean lesion length (about 15.5 mm for both), or pre-PCI minimum lumen diameter (MLD) or percent-stenosis.

Immediately after PCI, the stents achieved a significantly greater mean MLD (2.56 mm vs 2.30 mm in the balloon group, p<0.0001) and smaller residual stenosis (11% vs 20%, respectively, p<0.001).

In the ITT analysis, the significantly reduced late lumen loss in the balloon group was paralleled by a lower binary restenosis rate that only trended toward significance; there were no significant differences in TLR or MACE rates--although, Unverdorben emphasized, the differences achieved significance in the as-treated analysis.

Bailey called the study "intriguing" and a display of "remarkable efficacy" for the drug-delivery balloon not seen in other studies of localized intracoronary drug delivery. Based on the literature, however, the DES arm's TLR rate was "significantly higher than expected," he said. "The expected TLR rate should in fact be nearly in single digits, invoking the question of whether the anomaly that we see with this drug-eluting stent, even for in-stent restenosis, may in fact be a representation of a small population rather than a real trend."

Unverdorben had no disclosures. Bailey reports having ownership or partnership interest in Abbott, being on the speakers' bureau for BSCI and Abbott, and receiving research grants from St Jude.

  1. Unverdorben M. Randomized comparison of the SeQuent Please balloon catheter versus the Taxus stent in the treatment of in-stent restenosis--12-month follow-up of the PEPCAD II ISR study. American College of Cardiology Scientific Sessions/i2 Summit-SCAI Annual Meeting; March 31, 2008; Chicago, IL. Late breaking clinical trials 3.

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