Vikram S Kashyap, co-principal investigator of the ROADSTER 2 trial, today presented the final 30-day outcomes of the post-market approval study in a late-breaking trial session at the Society for Vascular Surgery (SVS) Vascular Annual Meeting (VAM; 12–15 June, National Harbor, USA). The data show the sustained safety and efficacy of transcarotid artery revascularisation (TCAR) with Silk Road Medical’s Enroute system. In this interview, Kashyap speaks to Vascular News about the procedure, and how TCAR trialists are hoping to make an impact for patients needing carotid revascularisation.
What is the idea behind TCAR, and how does it differ from carotid endarterectomy or transfemoral carotid stenting?
Transcarotid artery revascularisation is very different to other treatment strategies, such as carotid endarterectomy [CEA] or stenting [CAS]. This is a carotid stenting procedure, but it is via a different approach—a transcarotid approach—and the critical issue is that there is a protection mechanism to prevent cerebral embolisation which is using an extracorporeal reversal flow system, and importantly, clamping of the carotid artery below the sheath insertion that leads to obligate reversal flow in the carotid system during the intervention. So, this is very different to transfemoral CAS in that one does not have to navigate the aortic arch and the carotid arteries to get the devices there.
Secondly, and probably more importantly, is that there is absolute protection before any intervention is done; before a wire even crosses the lesion, reversal flow is accomplished so that debris is caught and removed via the system, and the blood is given back in the femoral vein.
CEA, which has been our gold standard for decades, is an operation that requires a longer incision and the interruption of blood flow temporarily. It is a longer procedure and a procedure that is a bit more intricate, quite frankly.
Following the initial ROADSTER 1 trial, what was important when considering the study design and endpoints of this post-market approval study?
There are a couple of important things to consider in terms of ROADSTER 1 and 2. Firstly, the pivotal study had a small group of patients, while ROADSTER 2 had a much bigger cohort, and with a considerable number of new operators. ROADSTER 1, for which I was also an investigator, consisted of a very small group of investigators, while the second trial includes 87 investigators—with 80% of them being new to TCAR, and they provided 70% of patients enrolled. This post-approval study was mandated by the US Food and Drug Administration (FDA), to see what the outcomes would be in a broader group of individuals, so that was part of how we designed the study. Secondly, there was concern that we could not replicate the data of ROADSTER 1 because it was such a select group of proceduralists, and so I think all of us are excited that the outcomes of ROADSTER 2 were as good, if not numerically better. I think therefore it is important to acknowledge the ROADSTER 2 investigators, who were phenomenal.
How do the final 30-day outcomes of ROADSTER 2 compare to the results of the previous trial?
I would suggest that the data are analogous, but it is not necessarily fair to compare the two studies and outcomes directly, as that was never the purpose of ROADSTER 2. Nevertheless, I think one can say that in a raw group of investigators with a fairly diverse group of patients, that we did get broadly similar results to ROADSTER 1.
I am impressed that we continued to have a very low event rate. Initially we thought that our good early results was due to the experienced investigators doing the early cases and getting great results. It actually turned out that even as we progressed and had more sites come on board with their patients, we still had outstanding outcomes. In ROADSTER 1 there was a total stroke/death rate in the pivotal group of 1.4%, and now in ROADSTER 2 this is 0.8%, which I think is very compelling. If you look at stroke death and myocardial infarction, it was 3.7% in ROADSTER 1 and now in ROADSTER 2 with 632 patients in the per-protocol group, the total number is 1.7%—11 patients. This number includes four strokes, one death and six with myocardial infarction, and the death importantly was not stroke-related but rather the patient had a ruptured aneurysm a few weeks after the procedure. So, neurological death rate was 0, in these 632 patients, and I think for any carotid revascularisation trial that is very impressive, especially a trial using carotid stenting.
The reported success rate was high, despite the majority of operators being new to this procedure. Why do you think that is, and do you think this adds particular value to your outcomes?
Firstly, one has to credit Silk Road and their training programme, where there was a very carefully thought-out plan on how to get new surgeons comfortable and expert at this technique—I think that is important to mention. Also relevant to that fact is that many of my colleagues who were co-investigators on ROADSTER 1 proctored new surgeons and gave them our best practices that we had learned in the pivotal trial and in the continued access. Thirdly, I think you can also say that perhaps this technique is pretty resilient, meaning this novel technology allows a new adopter to get pretty good fairly quickly. The learning curve is in other words short, and steep, as people get good within five cases or so, and are able to get outstanding outcomes.
Will ROADSTER 2 continue to follow up its patients in order to report on longer-term outcomes?
Yes, a one-year follow-up study is already in the works, that I am leading along with a couple of my co-investigators. We hope to report on this next year, and give some insight into the durability of TCAR.
It is interesting that—as opposed to stenting in other locations—after the first 30 days, if there is not a significant problem the issue of restenosis in the carotid bifurcation has not come up in other carotid stenting trials. So if a patient does not have an early deleterious outcome, it is likely that they will not have any. This is the thing that is maybe most exciting about this follow-up study: that there hopefully will be a very low rate of reintervention, as opposed to when you are talking about the femoral artery or the renals, or even the coronaries.
In terms of next steps, I believe we are at the point now where we need to do a prospective controlled trial. We have shown in a pivotal trial and a single-arm registry that TCAR is safe, technically feasible and adoptable by new surgeons, so I think a head-to-head comparison is the next step. Obviously, the narrative has now changed a bit. Three or four years ago, that comparative trial would have been TCAR versus CAS via transfemoral approach, and now I think we are at a point where we are instead thinking about TCAR versus carotid endarterectomy.