What is the reasoning behind the trial?

The SIRONA trial is actually a head-to-head comparison and the, really, very first head-to-head comparison of sirolimus DCB against a whole group of paclitaxel drug-coated balloon angioplasty. And the reason is actually that paclitaxel DCB in the treatment of claudicans in the femoral popliteal artery, it's the standard of care. Everyone accepts that's the standard of care. Very effective treatment, long-term patency. But still, there should be also the question, there's still the debate on the safety of the DCB coated with paclitaxel, not only for the Katsanos discussion of all-cause mortality. We also have seen this in our own meta-analysis that there is a certain signal of all-cause mortality, but I think there are other reasons why paclitaxel has some limitations. And first of all, the main limitation is that we are seeing a higher rate of limb amputation on the long-term use of paclitaxel. And also, if you have, and it's so effective that it also destroys the whole vessel wall, meaning even after stent implantation, you might have stent migration, you might have aneurysm in the femoral arteries. And these are, I think, limitations so that we should think about an alternative.

What was the study design and patient population?

Yeah, this is a randomized, controlled trial with a 1:1 randomization of the MagicTouch sirolimus-coated balloon against a group of DCBs — altogether seven. And we recruited, in a 1:1 randomization, 482 patients. And we are now looking at the 12 months results and the primary endpoints.

What were the key findings?

The key findings. First of all, I don't start with a secondary, I would like to start with secondary endpoints, is actually that it clinically works very well in comparison with paclitaxel-coated balloons, especially if you look at the TLR rate at one year. We did a Kaplan-Meier estimate and you're getting to very good results with a patency higher than 92%. And this is nearly equivalent the curve for both groups and also not statistically significant difference. So clinically, it works very fine. And also this we can see in change of Rutherford. What is Rutherford? It's a good estimate, clinical estimate about improvement of working capacities of our patients. And this was actually the improvement after one year was equivalent between both groups. But this is, clinically, we are pretty sure that both concepts are working well.

But now we are looking at also at the primary endpoints which is the efficacy endpoint and the safety endpoint. And we have two primary endpoints. As I said, the primary efficacy endpoint is primary patency with a pulse systolic velocity ratio less than 2.4 and no TLR at 12 months. Here we look at non-inferiority and also the primary safety endpoint which is a composite of clinically driven target vessel revascularisation, no major amputation and procedure and device-related death. Also we're looking here at non-inferiority.

Let me start with, everyone was waiting for the primary endpoint of efficacy, and this is actually quite astonishing. And we had for the sirolimus rate of 73.8% at one year as compared to paclitaxel with 75%. So the rate difference was only 1.2%. So the non-inferiority aim was reached with a p-value of 0.022. So we can confirm the efficacy endpoint was met. And also this was true for the, which we also expected for the composite safety endpoint. We had their overall safety of 9.4% for the sirolimus group as compared to 7.3% for the paclitaxel group — a little bit higher in in the sirolimus group. But this was not statistically, this was statistically, the difference was statistically, was not statistically significant. Meaning the non inferiority margin was met with p-value of 0.003. So, clearly, both balloons are at 12 months as safe than the other.

What are your take-home messages?

I think the main conclusion is regarding the primary endpoints. It's clearly both balloons are comparable in terms of efficacy as well as in terms of safety. And as I mentioned before, secondary endpoint, clinical endpoints shows really good results for both balloons. So in future you can decide, for the femoral popliteal artery, do I prefer with a lower-risk profile the sirolimus balloon or if I go for the paclitaxel-coated balloon? Both options, I think this trial head-to-head comparison means that both are comparable, and we compared against a whole group of those balloons on the European market which have also shown two year RCD data — so the real good players, so strong balloons. So in the daily business, it means you have the choice, and it's up to you to decide if these results are really convincing.

What further research is needed, and what are the next steps?

We are looking at five years follow up. I think it's always nice to reach good results after one year. It's very good and promising that we have reached the same level for both balloon categories, but now we really have to see how it's really performing the sirolimus balloon on long-term follow up. And we know that there's a late catch up for most of the paclitaxel coated balloons. People believe that sirolimus has a longer effect in the vessel ball and might have longer patency rates. So I hope next year at the TCT I can already present the two years data, and let's see how it looks like there, who is then ahead to each other. So we are looking for five years with one year intervals, and I'm really excited to see how it proceeds for the future.