Can you describe the ABSORB BTK trial?
This was a first-in-human study. We began working with this new investigational device approximately four years ago. Clearly, it is not on-label use for the lower extremity, so we went through the correct processes with our regulatory body in Australia, which is called the TGA, and had special access granted to use the device. The study itself was a single-center study and is a prospective cohort that we have been performing for slightly less than four years now. Currently, it stands at 49 treated limbs, representing 44 patients, and with a total of 65 bioresorbable scaffolds used.
What kinds of lesions are you treating and where?
For more than a decade, we have been using metal coronary drug-eluting stents (DES) to treat short, focal disease in the infrapopliteal arteries. Basically, we replaced the practice of using DES in simple, focal lesions in infrapopliteal arteries with use of the Absorb Bioresorbable Vascular Scaffold (BVS) (Abbott Vascular). These lesions are on the simpler side; we did not exclude any type of morphology, so there are some calcified lesions in the group. For the most part, the lesions were stenoses, with only around 15% being occlusions. This is consistent with what was seen in the randomized, controlled trials that have evaluated coronary drug-eluting stents below the knee, so it was a very similar group to that which had previously been evaluated.
What is the process in place for use of a BVS in the lower limbs?
When we began the program, we spent a lot of time with our coronary colleagues, who already had a substantial experience using the Absorb BVS. We learned a lot from their early experience and took that information to the lower extremity. It is a little bit different, in that of course we can use subtraction angiography, which gives us a higher quality image without the movement artifact of cardiac motion, and so probably we get better angiographic information than our colleagues working in the coronaries. During our early experience, we did not use any intravascular imaging. We made the observation that a ridged appearance of the blood vessel on subtraction angiography implies good wall apposition. As we started using optical coherence tomography (OCT) to confirm these findings, we realized that the ridged appearance was indeed a good indicator and method of determining good wall apposition. In those early days, we relied very much on non-compliant, high-pressure post dilatation to make sure we had good wall apposition, which I think is good practice. Certainly in our local cardiology practice, as people have used a lot of this device, they have moved away from OCT and intravascular ultrasound (IVUS), and just gone with that high-pressure post dilatation as a good method of achieving apposition.
What did you find in the trial?
At the outset, we were most concerned about safety and feasibility, so we looked at major adverse limb events and technical success rate. But it quickly became apparent to us that the Absorb was a safe device and that it was feasible to use in the lower extremity, so we focused on clinical endpoints. We adjudged these patients at predetermined time points of 1, 3, 6, and then 12 months ongoing, and we looked at them clinically, of course, and we also used duplex ultrasound to determine binary restenosis. We used a very sensitive peak systolic velocity ratio of 2.0 to define binary restenosis, and through that, we calculated primary patency, assisted primary patency, and looked at limb salvage. Close to a third of the cohort have now reached the 36-month time point of follow-up. The mean follow-up is currently 18 months. What we have released at the 2016 VEITH Symposium is our 24-month primary patency and target lesion revascularization (TLR) rates. Earlier in the year, we published a smaller experience and shorter follow-up period in JACC: Cardiovascular Interventions. At that point, we had a 12-month primary patency of 95%. With this larger group, the 12-month primary patency on Kaplan-Meier was 92.3% and 24-month primary patency was 84.9%. Freedom from clinically driven TLR was 97.1% at both 12 and 24 months.
How does that compare to what has been seen in trials using DES?
There are three randomized, controlled trials that have utilized metal DES, giving us a historical marker of the standard of care for these lesions. The trials range from 78 to 85% primary patency at 12 months. This means the primary patency we have seen at 12 months with the Absorb BVS is at least as good as that, if not better. In fact, at 24 months, our 84.9% primary patency is as good as what any other DES study has seen at 12 months. There are limitations to the work, of course (such as being a single-center study), but it is very promising, and suggests that this particular drug-eluting bioresorbable scaffold seems to do very well in infrapopliteal arteries.
How are you prepping the vessel for the scaffold?
We have always been fastidious about the vessel prep; more so, I think, than what we would have done with a metal DES, probably just because the properties of polymer are different. The metal DES tend to score the vessel as you inflate. We realized that the polymer wasn’t going to score the vessel, so we spend extra time at the predilatation stage. We tend to take a slightly undersized or size matched 1:1 balloon to start with and give a good long inflation. We use that to provide a good angiographic result before putting in the scaffold, but also to size the scaffold. We found it a more reliable technique than using quantitative vascular analysis (QVA), for example. If we are treating a vessel we think is going to be 3.5 mm, we take a 3 mm balloon, do a good long inflation, look for an angiographically pleasing result with hopefully no dissection or recoil, and then we will place the scaffold according to the IFU. We follow that up with a high-pressure, non-compliant post dilatation for about 30 seconds. We have already left the scaffold balloon up for 60 seconds, so really that post dilatation is just to get nice wall apposition.
What about deliverability?
It is more favorable in the periphery. I am not a cardiologist; I don’t do coronary intervention, but I understand there have been some deliverability issues in the coronary circulation. Not so in the periphery. For the most part, it is a fairly straight run. We do antegrade access routinely. We have a long sheath placed close to the lesion, so there is not much native tortuous vessel to traverse in order to get to the lesion. The most tortuous section in the infrapopliteal arteries is the proximal anterior tibial artery where it takes the arch. We found that the device tracks pretty smoothly around there for the most part.
Any final thoughts?
In this first experience, we have been quite conservative. We intentionally did not treat lesions longer than 5 cm. We haven’t treated bifurcations, but these results have made us more comfortable as we look to take on more complex lesions in our routine clinical practice. The next step for us is treating those longer lesions, starting to investigate how the scaffolds go in bifurcations, and expanding the practice. Also, we recently had a paper accepted at the Journal of Endovascular Therapy (in press) that is a report on our early technical experiences with scaffold deployment, focusing on good, safe technique for the lower extremity. We feel it is important to get the word out to anyone who is considering using the scaffolds in the lower limb. It is not on label in the U.S., but given that the Absorb has been approved for coronary use, we feel some people may explore it off label, so we are really keen to educate new users about how to deploy it safely to achieve best results.
Disclosure: Dr. Ramon Varcoe reports he is a consultant to Medtronic, Abbott Vascular, and Boston Scientific.
Dr. Ramon L. Varcoe can be contacted at firstname.lastname@example.org.