Cath Lab Digest - December 2007 - (Page 15) DECEMBER ON THE HORIZON Polymer-free Drug Delivery to the Vessel Wall: A Drug-eluting Balloon Catheter Cath Lab Digest talks with Martin Unverdorben, MD, Clinical Research Institute at the Center for Cardiovascular Diseases, Rotenburg an der Fulda, Germany Why might a balloon work better than I do want to make a clear distinction between both the Paccocath and the SeQuent™ Please balloons on the one hand and another paclitaxel-eluting balloon catheter (Eurocor, Bonn, Germany) which uses a different technology to deploy the drug to the vessel wall. To our knowledge, no clinical data-based testing in humans have been published yet, and some of the brochures that indicate clinical information show data that are identical with those from the PACCOCATH study. cardiologists will still use stents; however, they may either deploy the stent using the paclitaxel-eluting balloon catheter or dilate the vessel with the drug-eluting balloon following stent placement. The primary endpoint for both trials was 6-month late lumen loss. Why this endpoint instead of MACE? First of all, it is a statistical reason when designing studies. Six-month late lumen loss is a continuous variable. In order to detect a difference in a small trial, that is always a good thing to do. MACE, however, from a clinical perspective, is what really matters. The ultimate proof would be MACE, and we in fact did not observe any differences in MACE early on, i.e., after 30 days. However, we do observe significant differences after 6 months. Perhaps we will see a more pronounced difference after one year and three years. That is why this long follow-up period is part of the study design. There was some discussion at the TCT news conference regarding the use of late loss in PEPCAD I and II. It was argued that late lumen loss as an endpoint probably does not make too much sense because the late loss would be related to the amount of luminal gain during the procedure. Stents provide a greater luminal gain than balloons. If this statement was correct, and I do not think it is across devices, then I think the easiest thing to do to correct such a problem would be to not expand the stent as much — instead of a 0.3 stent expansion, perhaps 0.15 mm — in order to appropriately compare late lumen loss between stent and balloon. Nonetheless, we picked up the cue and will perform the suggested and some additional analyses in this regard in order to reach more clarity. Certainly, late lumen loss is different in balloons and stents. We will always compare apples and oranges because balloons and stents are different. However, they should not be seen as mutually exclusive; they are different arrows in the same quiver serving different purposes. You mean there are other issues besides the initial gain that may affect the amount of late lumen loss. Yes, for one reason, there is a polymer on many stents. With a drugeluting balloon, you avoid that issue. There was a low restenosis rate in PEPCAD I-SVD. Considering the excellent drug coverage provided by Martin Unverdorben, MD Dr. Unverdorben discusses the results of two trials which have shown a drug-eluting balloon to be associated with low late lumen loss and low major adverse events (MACE) in small coronary arteries, and superiority for late lumen loss and MACE to a drug-eluting stent for the treatment of in-stent restenosis. He presented initial trial data at TCT 2007 and shares his thoughts on the future of this new technology. Can you briefly describe the Paclitaxel-Eluting PTCA balloon catheter in Coronary Artery Disease (PEPCAD)-I SVD and II-ISR trials? These two trials follow a pilot study done by Scheller et al, published in the New England Journal of Medicine1 in 2006. Dr. Scheller compared plain old balloon angioplasty with a paclitaxel-eluting balloon in a small cohort of patients with in-stent restenosis. He found that patients who received the drug-eluting balloon had both significantly lower restenosis rates and major adverse cardiac events (MACE) such as myocardial infarction, bypass surgery, repeat angioplasty or death. PEPCAD I-SVD, the first of two studies I presented at TCT earlier this year, evaluated the use of a drug-eluting balloon catheter (SeQuent™ Please, B.Braun, Melsungen, Germany) for the treatment of small vessel coronary artery disease in 120 patients. PEPCAD I-SVD is a one-arm study, looking at the drug-eluting balloon as the first-option device to treat small vessel disease. If the result was not satisfactory, the subjects could be treated with any device, but a bare metal stent was recommended. After six months, de novo lesions treated solely with the drugeluting balloon showed a 5.5% binary restenosis rate and 6.1% MACE rate. In PEPCAD II-ISR, we directly compared the drug-eluting balloon catheter to the paclitaxel-eluting Taxus™ stent (Boston Scientific, Natick, MA) in 131 patients over six months for the treatment of in-stent restenosis. PEPCAD II was designed as a two-arm, prospective, randomized, controlled study. In the first arm, the drug-eluting balloon was a standalone device, but in some cases (10.3%), a stent had to be used if the initial result was unsatisfactory. The second arm of the trial was the assignment to the paclitaxel-eluting Taxus stent. In 6.2% the stent did not cross the lesion and a balloon catheter had to be used instead. Patients treated with the drugeluting balloon experienced a 3.7% in-stent restenosis rate and 4.8% MACE rate, as compared to patients receiving the drug-eluting stent, who experienced an in-stent restenosis rate of 20.8% with a 22.0% MACE rate. Is this the first time this device has undergone a randomized clinical trial? Well, yes and no. The prospective, randomized PACCOCATH ISR I and II trials, also presented at the TCT by Dr. Scheller, used a drug-eluting balloon featuring the same concept, but produced by a different manufacturer (Paccocath, Bavaria Medizin Technologie, Germany). a stent for drug delivery? First, the dose applied to the vessel wall by the balloon catheter is about three times higher as compared to the drug-eluting stent. Second, the balloon distributes the drug homogenously along the arterial wall, whereas in drug-eluting stents, the highest concentration is underneath the struts. Third, when a stent is deployed into the artery, usually the device stays there forever. Especially with the polymers, stents may be associated with a permanent alteration of the vessel wall. When a balloon is used, no foreign body remains behind. Still, based on the mechanism of restenosis, some situations do exist where you require a stent. I am not suggesting it is now all about the balloon and that we do not need stents anymore. The drug-eluting balloon will very likely be another device in our toolbox, but a sophisticated one. We most probably will end up with particular approaches and particular devices for particular types of lesions and patients. Moreover, I think there are also some general reasons why people would prefer a balloon over a stent. A balloon is a device that can be handled a little more easily than a stent, since it is thinner and more flexible than a balloon catheter carrying a stent. Second, there may be some financial advantage. For small vessel disease and in-stent restenosis, at least, it appears that the drug-eluting balloon is superior to the drug-eluting stent. In what other types of lesions might a drug-eluting balloon be appropriate (or not)? The paclitaxel-eluting balloon catheter may be especially beneficial in complex situations such as acute myocardial infarction, bifurcational lesions, and in patients with diabetes and or elevated white blood cells as a reflection of enhanced inflammation. However, other indications will be evaluated as well. In vascular dissection, Disclosure: Dr. Unverdorben reported no conflict of interest with regard to the PEPCAD trials and the SeQuent™ Please balloon catheter.
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