Cath Lab Digest - December 2007 - (Page 16) ON THE HORIZON DECEMBER the balloon, could operator issues play a part in contributing to the restenosis rate? PEPCAD I-SVD had a 5.5% restenosis rate without additional stenting, which is very low. That is an absolutely great number. One has to be aware that we talk about a pilot study with a relatively small number of subjects. But in general, having analyzed a couple of thousand angiograms in a quantitative angiography lab, I definitely do agree that the results are highly operator influenced. That is why I think the gold standard is still the prospective, randomized, controlled study design. I would also suggest using the same core lab in order to allow for an accurate comparison. This of course puts a question mark behind any historic comparison. Still, PEPCAD I’s 5.5% restenosis rate apparently puts the paclitaxel-eluting balloon catheter far ahead of many other products, which are associated with higher restenosis rates. I do not know whether the sponsor or someone else in the future will decide to run a prospective trial in small vessel disease comparing this drug-eluting balloon against some other interventional method. Unfortunately, that is not my call. I may only advise. What did you think about the outcome of the PEPCAD II-ISR trial? The balloon was superior when compared to the drug-eluting stent. It was a randomized comparison, it was a fair comparison. Whenever we decided we would exclude a patient for enrollment violation, we did so after the documents and CD of the initial procedure were available. So from the process point of view, the evaluation was well-executed with no bias. PEPCAD II-ISR shows the difference. It is a relatively small study with 60 versus 70 subjects in the astreated evaluation. The data are clear. I hope they can be confirmed in a larger cohort where the limitations of a pilot study do not apply. Has the PEPCAD-II trial in particular received a fair reception, especially since the balloon did so well against the drugeluting stent? First of all, I am always happy if someone scrutinizes our data, and challenges our data, because ultimately we want to help the patient. I actually expected more reservations. Our data were well received. On the other hand, if we take the PACCOCATH I and II trials by Dr. Scheller, THUNDER (which was in the peripheral arteries) by Dr. Teppe, and now PEPCAD I and II, the evidence is accumulating that this concept of drug-delivery to the vessel wall seems to work. Usually with a new concept, people are very enthusiastic, then they bounce back down before leveling off somewhere between the very optimistic and the very reserved positions. The device shows promising results and the data are surprisingly consistent in favor of the balloon — surprisingly in that we see a 0.19 mm late loss compared to a 0.18 mm late loss with both of the trials when using the paclitaxel-eluting balloon alone. We also observe a significant difference comparing the balloon to the Taxus stent. The Taxus stent actually fared a little bit worse than I thought it would in such a study. However, PEPCAD II-ISR is a prospective, randomized, controlled study and our data do not indicate a difference in baseline characteristics or any other bias. Ultimately, the balloon is a promising device. We simply need more data. The outcomes so far are not only a justification, but a clear indication that we should conduct more trials and obtain more clinical data. If these results can be confirmed in other studies, this paclitaxel-eluting balloon catheter would have a significant impact on patient care, in favor of the patients. However, I do caution about transferring the data to any other drugeluting balloon catheter (although any additional technology is welcome). What are your future plans? We will be working on collecting and computing the data from the two PEPCAD trials for peer-reviewed publication. There is one currently active trial, PEPCAD III, which is comparing the combination of a drug-eluting balloon and a stent in comparison to a drug-eluting stent. That is the only PEPCAD trial in which we are not involved as of today. There is also a study in diabetics, which is a randomized prospective study conducted in Asia, and another small, preliminary feasibility pilot study in subjects with bifurcated lesions, using the SeQuent Please balloon. These trials should give further indication if we are on the right track. The results of these studies will also allow us to plan a larger study in respect to one important issue, which is clopidogrel. What has not been emphasized to an adequate extent is that clopidogrel medication with the balloons was administered for shorter period of time than with stents. Right now the recommendation after paclitaxel-eluting stent deployment is around 12 months. In the PEPCAD trials, we used the drug only for 1 and 3 months with the balloon About the SeQuent Please™ B. Braun Melsungen describes its SeQuent Please drug-eluting balloon catheter, used in the PEPCAD I and II trials. Tell us about the SeQuent Please. The SeQuent™ Please is a drug-eluting balloon catheter from B. Braun Melsungen AG in Germany which delivers drugs directly to the lesion during angioplasty. The concept is based on a proprietary matrix technology. Rather than simply coating the balloon with drugs, 3µg/mm2 of the drug paclitaxel is embedded in a bioabsorable matrix. After balloon deflation, the matrix adheres to the arterial wall and facilitates the drug release to surrounding tissue. As there is no need for the sustained release of paclitaxel after the inflation, the matrix will dissolve immediately. Prior to the SeQuent Please, there was no effective way to distribute drugs to the lesion site by using a percutaneous transluminal coronary angioplasty (PTCA) balloon. While the drug-eluting stent has emerged in recent years as a treatment for coronary artery disease, it has been associated with complications. Recent studies have suggested that the polymer coating of these stents might be implicated in the reported complications. The SeQuent Please is polymer-free and bioabsorable. The proprietary matrix technology of the SeQuent Please is more effective than a simple drug coating of a balloon. After the inflation, the matrix will dissolve immediately so that no material is left behind that could potentially lead to complications later. Does operator usage differ at all from a standard non-drug eluting balloon? The use of the SeQuent Please drug-eluting balloon catheter is no different than that of a standard PTCA balloon catheter. With the SeQuent Please, we recommend a minimum inflation time of 30 seconds. There is no evidence to support that additional inflations would impart any additional drug benefit. However, an operator might employ multiple inflations in an effort to improve the angiographic outcome of the target legion. When is European CE marking and U.S. FDA approval expected? Although there are no guarantees, we’re hoping to gain CE marking approval by mid-2008. B. Braun is also committed to introducing this product to the U.S. market and are in the planning stages for the registration process. patients. So far, we have not seen any late thrombosis in more than 200 patients. This is also true for the PACCOCATH studies reported by Dr. Scheller. We may significantly save on clopidogrel administration, therefore also saving on cost and adverse events as a side effect of clopidogrel. Combining all the short-term studies together before beginning a longer, larger study, we could hopefully come up with a more precise idea as to what the duration of the clopidogrel medication should be. Ultimately, the drug-eluting balloon is an additional and promising approach, which cardiologists could use for treating their patients with coronary artery lesions, especially in the light of the current, vibrant debate about late thrombosis about when using drug-eluting stents. None of the device manufactures should claim exclusivity. No single approach treats all. However, if the concept would work as our data indicate, exhibiting promising clinical and angiographic results, financial benefits on the reimbursement side may also ensue. So this comes at the right time, and we will be happy to listen to anyone with suggestions about what we should and could do going forward. ■ Dr. Unverdorben can be contacted at sbu135@comcast.net. Recommended Reading 1. Scheller B, Hehrlein C, Bocksch W, et al. Treatment of coronary in-stent restenosis with a paclitaxel-coated balloon catheter. N Engl J Med 2006 Nov 16;355(20):2113-24. Epub 2006 Nov 13.
For optimal viewing of this digital publication, please enable JavaScript and then refresh the page. If you would like to try to load the digital publication without using Flash Player detection, please click here.