Dr Bruno Scheller

Compared with standard balloon angioplasty, the drug-coated balloon strategy appeared to suppress recurrent ISR over six months in a 52-patient study, published online November 13, 2006 in the New England Journal of Medicine and slated for the journal's November 16, 2006 issue. It was also associated with a significant decline in the one-year rate of adverse cardiac events, especially target lesion revascularization (TLR).

The study, from Dr Bruno Scheller (Universitätsklinikum des Saarlandes, Homburg/Saar, Germany) and associates, called the Treatment of In-Stent Restenosis by Paclitaxel-Coated Balloon Catheters (PACCOCATH ISR), had been presented in preliminary form at the EuroPCR 2005 meeting and was reported at the time by heartwire.

According to an accompanying editorial by Dr Edoardo Camenzind (University Hospital, Geneva, Switzerland) [2], PACCOCATH ISR "suggests that [balloon-]catheter-based drug delivery is a potentially promising approach to in-stent restenosis and demonstrates that old avenues of investigation may yield new solutions to persisting problems."

The study's angiographic and clinical outcomes were largely replicated in a similar analysis that combined the PACCOCATH ISR population with an additional 56 patients who were separately randomized but managed according to the same protocol [3]. In the so-called PACCOCATH-ISR 1-2 study, which Scheller reported here at the American Heart Association 2006 Scientific Sessions, late lumen loss at six months was more pronounced in both the coated- and uncoated-balloon groups compared with results in the original PACCOCATH trial, but the paclitaxel balloon's significant advantage persisted.

"For the treatment of in-stent restenosis, it's better not to have two layers of metal," Scheller said to heartwire. "And at bifurcations, it would be better not to have a stent in the side branches. I think those are the first uses [we envision] for the new balloon." It's too early to tell whether the drug-coated balloon procedure will cost less than conventional DES, Scheller said, but it may save some money indirectly by allowing a shorter period of subsequent dual antiplatelet therapy.

In the initial PACCOCATH ISR study, 52 patients with ISR of >70% severity and shorter than 30 mm in length in a single coronary artery were randomized in double-blind fashion to angioplasty using balloons with or without the paclitaxel coating, which contained 3 µg of drug per mm^² of balloon surface. The two patient groups were similar with respect to distribution of multivessel disease, the prevalence of diabetes and other conditions associated with restenosis risk, target-lesion measurements by quantitative coronary angiography (QCA), and acute balloon-inflation pressures and times. Clopidogrel was given to all for one month after the procedure and aspirin indefinitely.

Angiographic and clinical outcomes went in similar relative directions in the combined PACCOCATH ISR 1-2 analysis but reflected a greater overall degree of lumen loss and more clinical events. That, Scheller said, may have resulted from the greater overall complexity of, and therefore reduced expectations for success from, the lesions treated in the 56 patients who were added to the original PACCOCATH population.

It will take randomized trials much larger than PACCOCATH ISR 1-2 to determine whether the venerable balloon as a delivery system for antiproliferative agents can obviate contemporary DES for the treatment of ISR, not to mention de novo lesions or anatomically complex ones like those at bifurcations or in small or tortuous vessel segments. Scheller said there is an ongoing randomized trial in Germany testing the paclitaxel-balloon technique in small-vessel lesions and another that pits it against the Taxus stent in the setting of ISR. And in January 2007, he said, a multicenter trial will start enrolling patients to compare a paclitaxel-coated balloon carrying a bare-metal stent against a conventional DES for the treatment of de novo lesions.

In his editorial, Camenzind explains why de novo and complex lesions may present the paclitaxel-coated balloon with more of a challenge than it seems to have encountered with ISR in the PACCOCATH studies. The study excluded lesions with calcification, for example, and was limited to ISR lesions, which are "rather homogeneous histologically. The neointimal tissue has low cellularity and an extracellular matrix rich in proteoglycans, which may provide an ideal composition for drug absorption." Uptake of the drug may be less predictable in lesions with a more complex structure, according to Camenzind.