After Shockwave Medical announced that its intravascular lithotripsy (IVL) technology received pre-market approval for the treatment of severely calcified coronary artery disease from the US Food and Drug Administration (FDA), Cardiovascular News spoke to Dean Kereiakes, president, The Christ Hospital Heart and Vascular Institute, professor of clinical medicine, The Ohio State University (Columbus, USA), and the co-principal investigator of the pivotal DISRUPT CAD III study to discuss how IVL has the potential to revolutionise the treatment of problematic coronary calcium.
What are the challenges of dealing with coronary calcification, and how does IVL address these?
Calcium in the vascular system has never been a bigger problem than it is right now. That is a function of the progressively ageing population, the prevalence of diabetes, chronic kidney disease, and hypertension—all of these are factors that contribute to the development of vascular calcium.
Calcium in arteries increases the acute complications of any angioplasty procedure, whether this is in the peripheral or coronary arteries. It increases the incidence of arterial dissection, abrupt closure, perforation or rupture and also impairs short- and long-term outcomes following stent implantation by altering the symmetry, apposition and expansion of the stent. That is very important because the more the degree of calcium, the greater the likelihood of incomplete stent expansion.
If you think about what we are doing [when performing an angioplasty], we put a drug-coated stent in, which functions as a mechanical scaffold and a drug delivery platform. If that scaffold is not fully expanded, there can be inadequate drug delivery to the target. Incomplete stent expansion due to calcium is a “gift” that keeps on giving, resulting in death, myocardial infarction, and repeat revascularisation for years following the procedure.
Calcium also contributes to stent fracture which is a big problem. When stents fracture there are higher rates of thrombosis and restenosis. When you put all of those things together, calcium is a problem that continues to worsen clinical outcomes for patients who are treated with angioplasty and stents over a long period of time.
What is the advantage of using IVL in severely calcified coronary arteries?
The advantage that we have now with IVL—both generally and with coronary IVL in particular—is that, for the first time, we have something that is very predictable. As an original investigator for rotational atherectomy, orbital atherectomy, and even for laser, I have seen the whole gamut of technologies. IVL is reliable and it is safe, with extremely low to non-existent rates of perforation and no-reflow.
Most technologies are deployed by tracking a wire, but a wire is going to be biased. With IVL, you blow the balloon up to just 4 atmospheres of pressure, and the shaft of the balloon where the sonic pressure wave emitters are placed becomes centred in the artery. These sonic pressure waves extend circumferentially and transmurally across the wall of the vessel. So, these waves can access and modify calcium throughout the wall of the vessel and they do so in a centred fashion without extreme wire bias.
The outcomes that we see with this technology, I think, are clearly better. We didn’t do a head-on comparison in DISRUPT CAD III, we designed the next best thing, which is to use the pivotal trial for FDA approval of orbital atherectomy—Orbit II. We set out to enrol a similar population of patients using the same endpoints, the same definitions, and the same biomarkers. What we actually ended up doing was enrolling a worse population.
If you just look at lesion length or calcified segment length in the artery, in DISRUPT CAD III the target lesion length was 26mm on average, compared to only 18.9mm in Orbit II. Calcified segment length was 47.9mm compared to only 28.6mm—a dramatic difference. And yet, our 30-day major adverse cardiovascular event (MACE) rate was 7.8 compared to 10.4 in Orbit II. The rate of perforation, abrupt closure, and no reflow after IVL alone: Zero. Regardless of lesion length, IVL performs extremely well and differentiates itself from rotational atherectomy.
From an operator perspective—how steep is the learning curve for IVL?
If you ask an interventional radiologist, a vascular surgeon or an interventional cardiologist, what the most simple, primitive technology they use is, most will say it is a balloon—IVL is not much different.
I do not want to say there is zero learning curve, but when you look at the primary safety and efficacy endpoints, even device crossing, those three endpoints were no different in the first case in each of the centres [involved in DISRUPT CAD III], compared to the rest of the trial.
Nothing could be more simple than a balloon, and I think that is the genius of the technology. You take a leading-edge technology—intravascular lithotripsy—and you package it in a primitive delivery system.
How significant a milestone is FDA approval for patients with coronary calcification?
IVL was identified as a breakthrough technology, and it really is. It is safer, more effective and will continue to improve by optimising stent expansion, reducing early complication rates, and improving the late outcomes of stenting.
Published in JACC last week were the three year outcomes of the ULTIMATE trial, which used intravascular imaging to optimise stent deployment compared to just angiography. Over three years, the curves continue to diverge in favour of optimised stent outcomes.
When you look at the maximum calcified site in our 100 patient sub-study of DISRUPT CAD III, at the site of maximum calcium the average arc was 293 degrees. The average thickness of that calcium was 0.96mm, and the average stent expansion at that site was 102%. Never have we seen those kind of results in calcified vessels, where you have >100% stent expansion. Based on the ULTIMATE trial as well, this predicts excellent long-term outcomes.
The only limitation that will be perceived is hospitals responding to the price. I think hospitals may restrict access, or ask doctors to justify the usage until there is incremental reimbursement. Until then, hospitals will be reluctant in their allowance of physicians to utilise the technology. If not, physicians would use IVL all of the time, because it is safe, predictable, and easy.
Dean Kereiakes is a consultant to Shockwave, with no equity holdings.