Intravascular Lithotripsy Lives Up to Its Promise

Since intravascular lithotripsy (IVL) was first described in peripheral arterial disease, a growing evidence base has underlined its efficacy and safety as a vessel preparation technique. The data was reviewed on Tuesday morning by Erwin Blessing, Clinic Director at the University Heart and Vascular Center of the University Hospital in Hamburg-Eppendorf, Germany. Professor Blessing spoke to LINC Today to discuss the relevant research and give his take on how IVL fits into the toolbox for vessel preparation. 

Professor Blessing began by highlighting the importance of vessel preparation in general, especially regarding long-term patency in challenging lesions. “Preparation itself has gained tremendous recognition over the last few years, as we had an unmet need with the high bailout stent rate in challenging lesions,” he said. “We now know that in such lesions we have to invest a little more into the initial index procedure to provide sustained long-term patency, and that’s where preparation is key.”

Considering when to choose IVL as a preparation strategy – as opposed to other options such as standard balloon angioplasty with prolonged inflation, specialty balloons, or atherectomy – Professor Blessing drew attention to the mode of action of lithotripsy. Since the technology utilizes acoustic pressure energy to make microfissures in intimal and medial calcium, IVL is naturally only appropriate for calcified lesions.

“Obviously, noncalcified lesions are not going to respond to that technology, so patient selection is very important – there’s no role for IVL in fibrotic, soft, or thrombotic lesions,” he stated.

In calcified lesions where IVL is appropriate, Professor Blessing believes that this technology has certain advantages over atherectomy. “Atherectomy devices have quite a learning curve, somewhat of a complication rate, and they add complexity and cost to the procedure,” he commented. “That’s where IVL really comes in handy. IVL is a very easy to use, safe, and effective way to prepare calcified lesions throughout different territories.”

The challenges of vascular calcification are well recognized: calcium deposition in the intima and media can interfere with drug delivery, as well as limit compliance, raising the risk of flow-limiting dissections and perforation. This results in a greater need for stenting, but to compound this picture, calcification is also a risk factor for in-stent restenosis. IVL emerged as a novel technology to help address these issues, and Professor Blessing noted that the early hopes have not been disappointed. 

“In the field of peripheral arterial disease there are so many new kids on the block; we’ve seen many technologies come and then go within a couple of years because they didn’t live up to expectations,” he observed. “The jury was out with IVL to begin with – we needed solid clinical data to show it lived up to our expectations. We’ve now seen that with 2 very important studies.”

These 2 studies were the DISRUPT PAD III randomized controlled trial (RCT) and the DISRUPT PAD III observational study. Professor Blessing drew attention to the former first, emphasising the value of RCT evidence. 

The DISRUPT PAD III RCT enrolled 306 participants with moderate or severe femoropopliteal artery calcification; patients were randomized 1:1 to receive vessel preparation with either IVL (Shockwave Medical Peripheral Lithoplasty System) or percutaneous transluminal angioplasty (PTA) prior to drug-coated balloon treatment or stenting. The primary endpoint was core lab-adjudicated procedural success, defined as residual stenosis of ≤30% without flow-limiting dissection.

Initial analysis of acute outcomes revealed significantly higher procedural success in the IVL group (65.8% IVL vs 50.4% PTA; P=.01). Looking into this in more detail, the occurrence of flow-limiting dissections was higher in the PTA group (1.4% IVL vs 6.8% PTA; P=.03), while the percentage of lesions with residual stenosis ≤30% was higher in the IVL group (66.4% IVL vs 51.9% PTA; P=.02). The frequency of stent placement was also notably lower in the IVL group (4.6% IVL vs 18.3% PTA; P<.001).¹ Follow-up analysis revealed a sustained benefit of IVL: primary patency in the IVL group was higher at 1 year (80.5% IVL vs 68.0% PTA; P=.017) and 2 years (70.3% IVL vs 51.3% PTA; P=.003).²

“This superior performance at 1 and 2 years was primarily due to the lower need for bailout stenting, which was included within the primary patency endpoint,” commented Professor Blessing. “To sum up, there was a clear technical benefit provided by IVL – we saw superior results with fewer stents implanted.”

This RCT data is very valuable, as it demonstrates the benefit of IVL compared to standard PTA treatment. However, Professor Blessing noted that the subpopulation included in the trial will not reflect the full picture seen in the clinic. “As important as RCTs are, there’s an element of cherry-picking,” he acknowledged. “There are so many exclusion criteria that the results will not fully represent the real-world scenario where we see long lesions and we treat critical limb ischemia (CLI) patients and dialysis patients. Also, what works well in the femoropopliteal area doesn’t necessarily work so well in the iliacs or below the knee. So, we needed more real-world data to answer these questions.”

Real-world evidence was provided by the DISRUPT PAD III observational study, a prospective, multicenter, single-arm study assessing the acute safety and efficacy of the Shockwave Medical Peripheral IVL System for vessel preparation in calcified, stenotic lower limb arteries. Analysis of data from a total of 1367 patients revealed very similar outcomes to those observed in the DISRUPT PAD III RCT. Specifically, in terms of diameter stenosis, the observational study found a decrease from 81% pre-procedure to 33% post-IVL and 24% after final treatment. In the RCT, these values were 85%, 27% and 22%, respectively.^3,4

“Overall, the observational study findings were very comparable to the RCT results,” summarized Professor Blessing. “Note that the comparison is limited to acute technical success, as we don’t have follow-up data to 1 or 2 years for the observational study. But the acute technical success is very comparable.” 

It is encouraging also that this picture was maintained into subgroup analysis, Professor Blessing remarked. “Looking at the data, we still see very comparable results across different territories – the iliacs, common femoral artery, superficial femoral artery, the popliteal, and below the knee. And the same is true across different types of challenging lesions: whether they’re long, eccentric, occlusive, or severely calcified. And across different groups of patients, including CLI patients, dialysis patients, and renal patients. Altogether there’s very solid data that we can relate to the real-world situation.”

Professor Blessing next moved on to consider ongoing research that will shed more light on the safety and efficacy of IVL. He drew attention to the DISRUPT PAD BTK II study, a prospective, multicenter, single-arm study of the Shockwave Medical Peripheral IVL System for the treatment of calcified, stenotic lesions below the knee.⁵ This study will provide more real-world evidence on a difficult-to-treat patient population, which will be valuable as research on treating these patients is currently very limited. 

“It’s positive that this study aims to include at least 80% patients with critical limb-threatening ischemia (CLTI),” Professor Blessing said. “It’s important to look at the CLTI cohort because there’s so much more unmet need – we’re talking about limb salvage in these patients. The study will also include patients on dialysis, who have been excluded from almost every single trial on endovascular treatment. We have very little data on these patients, and the amputation rate in this population is tremendously high.”

Overall, Professor Blessing is optimistic about the future of research on IVL. “I would expect that the wealth of data is going to increase and the technology is going to improve,” he predicted. “I would expect a confirmation of the already rather convincing picture we have, with more data on specific subsets of patients who are difficult to treat and have historically been excluded from trials.”

REFERENCES

1. Tepe G, Brodmann M, Werner M, et al. Intravascular Lithotripsy for peripheral artery calcification: 30-day outcomes from the randomized Disrupt PAD III Trial. JACC Cardiovasc Interv. 2021;14(12):1352-1361. 

2. Tepe G, Brodmann M, Bachinsky W, et al. Intravascular lithotripsy for peripheral artery calcification: mid-term outcomes from the randomized Disrupt PAD III Trial. JSCAI. 2022;1(4):100341.

3. Adams G, Shammas N, Mangalmurti S, et al. Intravascular lithotripsy for treatment of calcified lower extremity arterial stenosis: initial analysis of the Disrupt PAD III Study. J Endovasc Ther. 2020;27(3):473-480. 

4. Armstrong E, VIVA Late Breaking Clinical Trial 2022. Data available on the Shockwave Medical website at: https://shockwavemedical.com/clinicians/usa/peripheral/clinical-evidence/pad-iii-os.

5. Disrupt PAD BTK II Study with the Shockwave Peripheral IVL System. ClinicalTrials.gov identifier NCT05007925. Available at: https://clinicaltrials.gov/ct2/show/NCT05007925; accessed May 2023.