Research at VEITHSymposium: Lithoplasty From Shockwave Medical for Treating Heavily Calcified Lower Extremity Occlusive Lesions

In September 2016, the Shockwave Medical Lithoplasty System received clearance from the U.S. Food and Drug Administration (FDA) for use in the peripheral vasculature, including the iliac, femoral, ilio-femoral, popliteal, infra-popliteal, and renal arteries. The Shockwave Medical Lithoplasty System uses lithotripsy to disrupt both superficial and deep vascular calcium.

What appeals to you about the use of lithoplasty technology for heavily calcified lesions?

The Shockwave Peripheral Lithoplasty device works in a different way than other devices such as atherectomy or a cutting balloon, yet its platform is a normal balloon catheter. We do not take calcium away with the use of this device, but create microfractures in the calcified wall. Thus, there is no risk of distal embolization and we do not have to place filters. The idea is that we alter the calcium by delivering acoustic waves into the vessel wall. In addition, by inflating the balloon and delivering pulses to the vessel wall, we can also tackle calcium that is not directly in the lumen, but in the media. The actual inflation pressure of the balloon when doing percutaneous transluminal angioplasty (PTA) is quite low. We deliver the pulses while inflating the balloon up to 4 bars followed by dilatation up to 6 bars, which is low pressure versus treating calcium with balloons only, where we use high pressure, 18 or 20 bars. So with Lithoplasty technology, the pressure to the vessel wall is quite low, and therefore, most likely, we damage the vessel wall to a lower degree compared to other technologies. 

Can you tell us some of the highlights of DISRUPT PAD?

This was a two-phase study, and the only difference is that PAD II is a bigger study, with 60 patients compared to 35 patients, and PAD II has one-year follow-up, which is not true for PAD I. The one-year follow-up data are not yet available. The main goal with this technology was to achieve a good result in moderate and severely calcified arteries as a standalone therapy. Only one patient had to receive a stent out of 95 patients total, resulting in a significant reduction in the use of stents for this patient population. 

When you say standalone therapy, what about predilatation?

Predilatation and post dilatation were done in a very low number of patients. The Shockwave device is a normal balloon that has good pushability characteristics compared to other normal PTA balloons on the top end. If I had a wire across, I was able to cross with the catheter in all cases. So predilatation is not mandatory and generally not required.

The whole case can and should be done with the Shockwave catheter. The standard treatment is to deliver 60 pulses at one location. You can deliver additional pulses to maximize dilatation of the artery, known as acute gain. The impact is a reduction in the need for post dilatation. Of course, with traditional PTA balloons, we could theoretically apply higher pressure to dilate the artery, but that’s all. The Shockwave device can treat both superficial and deep calcium using acoustic waves, resulting in high acute gain. Again, only one stent was needed to treat a single dissection, which represents a reduced need for an implant to treat a dissection, recoil and/or some mechanical issue.

Can you describe the lesions included in the trial?

Lesion length was around 7 cm, and we treated only moderate and severely calcified lesions. The burden of calcified disease was significant, with severe calcification involving both sides of the artery in 55% of the patients and an average length of calcified length of 9 cm. In addition, we had total occlusions in 19% of patients, and these had a similar treatment effect as other patients enrolled in the study.   

Do you have to cross the lesion before doing Lithoplasty?

That’s the nice thing about the procedure. It’s like a normal balloon angioplasty, and with a normal balloon angioplasty, you generally cross with a wire, either with a normal catheter as a support or with a support catheter. Then you just have to confirm that you successfully crossed the lesion and then the wire is in place. If, for instance, we started with the .035-inch wire in order to cross, we have to change to the .014-inch wire, place the .014-inch wire, and then just push the catheter through the lesion. This is possible with no predilatation, I would say, in a majority of cases. Then we inflate the balloon to 4 bars, deliver 30 pulses, and inflate to 6 bars, then leave it in place — similar to what we do for PTA — for 1 to 3 minutes, and then deflate. This sequence is repeated to deliver a minimum of 60 pulses in any one location of the vessel. The balloon length measures only 6 cm, so if the lesion length is longer, then we go to a different location and do the same. We then do an angiogram and if there is still a residual stenosis, it might be that we should go again and deliver more pulses. 

In the trial, patency was 100% at 30 days, then at 6 months down to 77%. Based on your knowledge of this disease, what do you anticipate moving forward?

On the one hand, that 77% patency does not sound so great, especially if we think about a mean lesion length of 7 cm. On the other hand, we are treating patients that are normally excluded from other trials, so we have little data in trials on moderate to severely calcified arteries. We are dealing with a totally different patient cohort here and that is something that must be taken into account. With Shockwave, we do have a great device to obtain a good result with minimal stents, but it is not mainly designed to reduce restenosis. Of course, it theoretically addresses the aim to reduce restenosis in that way we harm the vessel less, so there is less stimulus for neointimal proliferation. Still, no drug is delivered for prevention of restenosis, so my recommendation is to combine the Shockwave device with the use of a drug-coated balloon. We would use the Shockwave device in order to get a good result with no stent, and then take a drug-coated balloon to deliver an anti-restenotic agent in order to obtain even higher patency results. This will be looked at in a study called DISRUPT PAD III, announced during the TCT meeting in October 2016. DISRUPT PAD III will be a 300-patient study, and Bill Gray and I will be co-principal investigators.

What are the issues with drug-coated balloons in calcium?

Here, we are tackling a patient cohort that is already excluded from other studies, as I said, so we cannot have any comparison with any other studies. Nevertheless, if we just look into the data regarding drug-coated balloons in calcified arteries, we also know that especially in circumferential calcium, a drug-coated balloon does not work as well as in other arteries. The theory here is that by cracking the calcium with the Shockwave device, we might enhance the uptake of the drug and possibly enhance the efficacy of drug-coated balloons in calcified arteries. Normally with drug-coated balloons, we stay away from calcified arteries, because we know that drug-coated balloons don’t work as well in these patients. In general, calcified arteries are very often stented, and while stents might look quite nice, the problem with stents is the calcium is still there and might press the stents together. If the stent restenoses, retreatment options are limited. With the Shockwave device, we try to not apply stents, even when treating severely calcified arteries. In PAD III, we will also use drug-coated balloons. In the future, within the next 2 to 3 years, almost no patients, at least in the superficial femoral artery (SFA) and popliteal arteries, will be treated without local drug prevention of restenosis, because this approach is superior to either stents or plain old balloon angioplasty.

Any final thoughts?

We are waiting on the one-year data, which will be presented by the principal investigator of the PAD II study, Thomas Zeller. The PAD III study will be started soon, and will take place at 45 sites in Europe, the U.S., and New Zealand. 

Disclosure: Dr. Gunnar Tepe reports study support from Shockwave (participation in PAD II) and that he will be the co-principal investigator of the PAD III study starting in 2017.

Dr. Tepe can be contacted at gunnar.tepe@ro-med.de

About the DISRUPT PAD Study 

The DISRUPT PAD Study, a single-arm, two-phase, multicenter study evaluating the safety and performance of Shockwave Medical’s Lithoplasty System in calcified peripheral lesions, enrolled 95 patients at 11 sites with symptomatic femoropopliteal lesions up to 15 cm in length. 

• Primary safety endpoint: Freedom from major adverse events (MAE) through 30 days. 
• Primary performance endpoint: Procedural success, defined as <50% residual diameter stenosis, with or without adjunctive balloon angioplasty therapy. 
• Key secondary endpoints: target lesion revascularization, target lesion patency by duplex ultrasound defined as freedom from greater than 50% restenosis, and functional outcomes. 

Six-Month Data

Clinical data from the study showed no major amputations, perforations, thrombus, or distal embolization events. Stent utilization due to a flow-limiting dissection following Lithoplasty was limited to 1% in study population composed of moderate or severely calcified lesions. Primary effectiveness results demonstrated 100% procedural success, defined as residual stenosis <50%. An exploratory endpoint of procedural success, defined as residual stenosis <30%, was achieved in 89.5% of lesions, with an average residual stenosis of 24% and acute gain of 3.0 mm (average reference vessel diameter of 5.5 mm). Six-month patency assessed by duplex ultrasound was 77% with target lesion revascularization of 3.2%.