The XIENCE V EXCEED Trial: Acute Performance, Deliverability and Resource Utilization in the Cath Lab

Can you describe the EXCEED trial and its purpose? There are two components of the post-marketing evaluation of Abbott’s Xience V stent. First is the Xience V USA program, which is looking at long-term clinical outcomes in about 8,000 patients. Supplementing that study is the EXCEED trial, a real-world trial looking at how cath labs and physicians are using the Xience V stent in real practice. Specifically, EXCEED studied the acute performance of the stent and resource utilization in the cath lab in patients receiving the Xience stent. What we mean by ‘acute’ is really the performance of the stent during the procedures. In other words, the study was finished as soon as the patient left the cath lab. It only looked at how things happened inside the lab. The primary endpoint of EXCEED was overall operator or physician-determined deliverability and performance of the Xience stent, assessed by a performance evaluation questionnaire. Physicians answered 13 questions immediately after the case was over, relating to details about how the stent performed during the case. In addition, procedural success was also indicated by the physician if the lesions treated had a final stenosis of less than 50% without any major complications during the procedure. EXCEED looked at all comers, and had virtually no exclusion criteria. How many patients were enrolled? Almost 2,500; the exact number of patients we have data on is 2,488. The trial involved 83 centers in the United States. What is important about the EXCEED trial? As we get newer-generation drug-eluting stent technology, there may be differences such as pricing. We also know that there may be differences in long-term outcomes with restenosis and complications, maybe even stent thrombosis, although that is yet to be determined. But no one has looked at whether or not the impact of better deliverability — i.e. better stent design — translates into less resource utilization, less cost, shorter procedure times, and better outcomes in the cath lab and in the procedure itself. EXCEED is the first study I am aware of that looked at these things in a large scale, with a newer-generation drug-eluting stent. The primary endpoint was not surprising. The acute procedural success rate was 99.3%, with no differences observed among patient subgroups. In addition, in 99.2% of cases, the operators rated the acute performance and deliverability as “excellent” when compared with first-generation drug-eluting stents. Also of importance, the in-lab rate of serious adverse events was only 0.8%. Data were then compared against the American College of Cardiology National Cardiovascular Data Registry (NCDR) database? Yes. EXCEED is a post-market surveillance trial. The idea was to literally capture all comers to the cath lab, so we wanted investigators to enroll every consecutive patient that received a Xience stent in their lab. The trial was open-label, measuring outcomes, assessing the success of everything else. At the end of the study, we compared our data to a comparable group of patients that received a first-generation drug-eluting stent, Cypher and Taxus, using NCDR data. Specifically, we looked at NCDR data from the same time period that the EXCEED trial was taking place, so the learning curve of how to deliver a drug-eluting stent from the operators was the same. We compared it to a cohort of 150,000 patients in the NCDR who received first-generation drug-eluting stents during the same time that EXCEED was enrolling. The two groups’ characteristics were fairly well matched up. So the time period of the first-generation stent data was the exact same time period as the newer generation stent data? Yes. EXCEED looked at patients that received Xience stents from the middle of 2008 to the beginning of 2009. We then went to the NCDR and obtained data on patients from the middle of 2008 to early 2009 treated with first-generation stents. We were careful to compare the same time period because, as you know, cath labs have changed their processes. We interventional cardiologists keep learning how to better deploy drug-eluting stents and how to optimally perform PCIs. We didn’t want any learning variables in the mix. What did you find when you looked at the two groups (EXCEED and the NCDR data)? There were two things that we looked at in comparison to the NCDR. One was contrast usage. We found a 30% reduction in the amount of contrast used in the EXCEED cohort compared to the NCDR cohort. The other was fluoroscopy time, and we found a 26% reduction in fluoro time in the patients receiving the Xience stent in EXCEED compared to those that got first-generation drug-eluting stents. What is it about Xience that you think has led to these results? A great deal of it has to do with stent design. Operators are dealing with a stent that has much thinner struts than the first-generation drug-eluting stents. The balloon technology is newer. The stent itself is designed to be more flexible and more deliverable. I’m just speculating here, but perhaps there is less of a need to pre-dilate, perhaps less of a need to use a buddy wire or an extra backup guide catheter to deliver the stent, and then that leads to less contrast use and less fluoroscopy time. We are currently trying to dive deeper into this analysis and find out exactly what it is that has made these differences so profound. Tell us about the patient population in EXCEED. The trial had a very rapid enrollment, and all investigators were instructed on multiple occasions to enroll every patient. Patient complexity was high. In EXCEED, over 57% had prior bypass surgery or prior PCI. The average age was 65 years old. We had almost 39% diabetics. Forty percent had multi-vessel disease. Over half of the lesions treated were class B2 or class C lesions. These were complicated patients — they weren’t highly-selected patients that you might find in a pivotal FDA approval trial for a new stent. EXCEED data was compared against a cohort of patients who were getting first-generation drug-eluting stents. You could argue that there is a bias among interventionalists that if you anticipate a lesion is going to be difficult to treat, you are going to use a newer-generation stent, because of the perception that they are more deliverable. Even with that potential bias, we saw a significant improvement in contrast use and fluoroscopy time in patients receiving the Xience stent. How should this trial impact practice? Should it impact the types of things being measured in the cath lab? Yes, the trial raises a lot of important issues. Each lab should take a good look at their resource utilization when they are performing PCI, and what predicts the amount of resources being utilized. That’s important, not just from an economic perspective, but it is also important for patient safety reasons. People ought to be looking at the amount of materials being used, not only in terms of guidewires, balloons, and stents, but also the amount of contrast and the amount of radiation to which we are exposing our patients. If you consider what we can do to decrease resource utilization, EXCEED trial data certainly suggests that the stent choice can have a significant impact on resource utilization, and contrast and radiation exposure to patients. This is a hypothesis-generating study that might lead to more studies in the future, focused on these things as primary endpoints in addition to traditional endpoints of clinical events at 6 months, a year, and beyond. Any plans for additional analysis? Right now, we are working with the NCDR to hopefully add some more sophistication to our analysis in terms of matching up patients, and do some modeling that might get us a better way to measure the economic impact of Xience versus first-generation stents. Very preliminarily, we are hoping to have some data to present early this year. How did working with the NCDR come about? We contacted them about helping us with analysis and they’ve been very accommodating and helpful. I would encourage other investigators to consider them as a great resource for looking at these types of comparisons. Disclosure: Dr. McPherson discloses he serves as a consultant for Abbott Vascular. Dr. McPherson can be contacted at john.mcpherson@vanderbilt.edu

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