Honestly, though, for everybody in this room, these are probably the two most important trials for you to be aware of and know a little bit of the inner workings of. So hopefully, we can do this and get everybody on with their evening. So I just always step back and think about where we are as a field, and if you look at what we do with cabbage versus corn intervention in the evidence pool, we've had 23 randomized trials, 13,000 patients. What do we have for CLI? Well, up until the last six months, we had one trial, which was done in the late 90s, early 2000s. And now we have three, 2,600 patients. We have now Basal-2 and Bestial-I, which I'll cover in the next few minutes. So Bestial-I, if you're not familiar, this is a study of surgical bypass versus endovascular treatment for infrainguinal CLTI, 1,830 patients. This took about eight years to enroll. There were 1,400 patients in Cohort 1, which was a venous bypass group, and then in Cohort 2, which was a terminated, underpowered group of alternative graft types, including synthetic The primary endpoint, which differs from the basal trials, which I'll discuss, was a composite of both amputation-free survival and major intervention. Findings for the Bestial-I trial are displayed in these figures here. I only show you Cohort 1 data, which is the venous bypass group, which is probably the most relative. And at 2.7 years, there was a superiority of surgery over endovascular treatment, which was primarily driven by major reintervention, which I'll speak about later in this talk. And Cohort 2, which was the synthetic bypass grafts, underpowered, shows no difference between endovascular and surgical bypass. So just last month, we had the results of the Basal 2 trial published in Lancet, and this, again, was another ongoing trial demonstrating the benefit of a best endo approach, as they call it, versus a surgical vein bypass approach. But this was a CLTI population of only infrapopatil lesions, so you had the ability to fix inflow, but the randomization occurred at the infrapopatil segment. And the primary endpoint, again, was amputation-free survival, which is an endpoint that we commonly are used to thinking about in the CLTI space. In this study at 3.3 years, the primary outcome actually favored a best endovascular treatment approach, which was primarily driven by greater survival among those treated with an endovascular treatment versus a vein bypass group. And I just note that there's about a year difference in amputation-free survival if you're randomized to a best endo approach versus a surgical approach. So how do we reconcile the differences between these trials, because we don't have a lot of data here. And so I'm just going to summarize a few things that I think are salient differences. It may not explain why we have two very discrepant findings, but it does suggest some of the differences can be driven by how these trials were conducted. So starting from the top CLTI population, just to remind yourself, basal CLI had infraengland disease, not infrapopatil disease. So about 55% to 60% of patients in basal CLI had an infrapopatil lesion intervened upon. Basal 2 is a pure infrapopatil disease population. And I think everybody can reflect on their own CLTI populations, which represents their practices the most. Trial setting, basal CLI was a U.S.-related based trial, basal 2 is a U.K. study. And I'm not sure how relevant those differences are, but there are some treatment practice differences including how often people stay in hospitals and the risk of the patients. In terms of sample size, basal CLI is the largest trial to date, 1,434 patients in the cohort 1, which is the venous bypass group, basal 2 had 350 patients. And then endovascular technical success rates, which I think we all have some pause about, basal CLI was 85% in cohort 1, 80% in cohort 2. Basal was slightly better at 87%, but again, an infrapopatil segment, not also including the above-the-knee space. One big thing that stood out to me about these differences is moving from an amputation-free survival to a composite endpoint that included major re-intervention. And I think a lot of us have different opinions here, and even my close colleagues will make a case that amputation-free survival is not sensitive enough. I feel differently personally, and I'll show you why in this study. So in basal CLI, out of the gates, this was a powered study that showed superiority of surgery. So how that study was designed was with the hypothesis that surgery was going to be endovascular treatment. Technical failure and need for major re-intervention was not centrally determined. So many of these cases had a failure to cross on the operating room table and went to bypass even though they were randomized to endovascular treatment. If you think about 15% to 20% endotechnical failure rate, I don't know how all of ourselves look at our own practices. I'm sure we all think we're almost 100%, you know, but I think that if you look back at basal 1 that was done in the late 90s with only balloons, it was a 20% technical failure rate at that time, and then also a 90% success rate for surgical bypass. So how do you really get endo to win here? Pretty hard. When you have 15% to 20% out of the gate, a fair 16% of them cross over and have an event rate out of target, and you have pretty much a pure surgical success rate. And so again, just looking at on the left side, basal 2 as an amputation-free survival endpoint, and basal 1 and basal 2, the basal 1 trial, we saw really equivalence over time. Basal 2, you start to see those deaths accrue in the peri-procedural period and the curves separate. So if you look on the right at best CLI, you can see that on the y-axis, if you focus on that figure on the bottom right, you're coming out of day one with a separation of curves. So you already had a fair amount of events that occurred in the endovascular treatment group that would switch over to surgery as a major intervention, which again is hard to reconcile. In terms of the representativeness of non-surgical specialties, best CLI was 86% vascular surgeons, 75% of the endo procedures were done by vascular surgeons. And I show here on the right what the makeup looks like among the population of Medicare beneficiaries treated in the U.S. for CLTI. We can see that cardiologists represent about 25%, interventional radiologists about 12%, 55% vascular surgery. In contrast, basal 2, 84% of endo is performed by interventional radiologists. Now, cardiologists don't typically perform vascular procedures in Europe, so the endovascular treatment is primarily driven by interventional radiologists, and you're more in the UK portion of the continent. Generalized ability of patients enrolled, I showed this data earlier today. Again, this trial for best CLI took 150 sites, 5-plus years, 2,500 patients to get down to 1,800, eventually randomized, and most sites only enrolled about 10 patients per site. So if you think about this on a site level on the right here, these are all the top-enrolling sites in best CLI that we found in the Medicare cohort. In red are the number of trial patients that they enrolled during the study period. In blue is the number of patients they treated with CLTI during the study period of only Medicare coverage, so there is a larger pool. So you can see that the generalized ability of this study is a fragment of our CLTI population, and I will note that if you look at the basal audit that occurred when they did that first trial, only about 15% of patients evaluated actually were eligible for enrollment. So this is an important trial. These data are really important, but how applicable they are to our general practice is probably a smaller portion. I just want to end, and again, I think it's really important for all of us to be balanced about what these trial data look like. I think I was really bothered by anybody saying that endo is the only way to go or anybody saying surgery is the only way to go, and I just highlight on this slide that we know that we live in an amputation epidemic, and we have mortality rates that are incredibly high at one year. We know vascular care differs depending on where you live in the country, and that should not be the case, and we also know who you are also depends on the severity you end up presenting with CLTI. So these are the pearls I'd like to end on, and again, my hope here is to be balanced about how we move forward with these data. I think that being grafting and bypass surgery are important revasculation strategies that we've underutilized, and I think vascularized is a good reminder that when appropriate, we really should be thinking about this strategy. I think there are a lot of other considerations, though, that we all know in our own practices that drive our treatment decisions. A lot of these are patient preferences. They don't want to stay in the hospital for long. They don't want to be under general anesthesia. We know we have trouble with access, costs, ICU, and hospital time, and so we need to really tailor our treatment strategies to the patient. I think we should be probably screening more frequently for suitable veins, but I don't know what the cost will be at the end of the day, and in the end, really, we should be able to come together as a more general community to make these decisions, and I think we're moving there, but I don't think we're totally there yet, and I hope these trials are interpreted with that in mind. So thank you very much. Sorry again to end on data, but I hope that was helpful. Thank you.

infrainguinal chronic limb-threatening ischemia

BestCLI trial

surgical bypass

endovascular treatment

Basal 2 trial