A sub-analysis of the DISRUPT CAD III clinical trial, investigating use of Shockwave intravascular lithotripsy (IVL) in severely calcified long coronary lesions, has found that the technology achieves statistically similar rates of safety and efficacy in both long and short lesions.
The findings were presented by Matthew J Price (Scripps Clinic, La Jolla, USA) during a live abstract session at the Cardiovascular Research Technologies meeting (CRT 21 Virtual, 13 February–24 April), and were broadcast shortly after the receipt of US Food and Drug Administration (FDA) pre-market approval for the use of IVL in the treatment of severely calcified coronary artery disease.
Price described the patients as “one of the more complex lesion subsets ever studied in a prospective FDA registration study”, and said that the study’s findings indicate that IVL—which uses acoustic waves delivered via a balloon catheter to disrupt calcified plaque—is an attractive therapy to address severely calcified lesions across a spectrum of lesion lengths.
The sub-analysis looked at patients enrolled in the prospective, observational, single-arm DISRUPT CAD III study, that demonstrated the safety and effectiveness of IVL to optimise stent deployment in patients with severely calcified de novo coronary stenoses. The study team stratified a cohort of 384 patients by the median lesion length of the DISRUPT CAD III population (25mm), comparing the outcomes in patients with shorter lesions (<25mm) to those with longer lesion lengths (≥25mm), with a primary endpoint at 30 days.
“We all know that severe coronary calcification within coronary lesions impedes both stent delivery and deployment which can in turn impair stent expansion which is a significant predictor of subsequent stent thrombosis and restenosis,” said Price.
“Long calcified lesions are therefore inherently more complex, and are associated with relatively higher MACE [major adverse cardiovascular event] rates, and lower procedural success rates following treatment with either balloon angioplasty, rotational, or orbital atherectomy.”
Price detailed that the primary safety endpoint of the trial was freedom from MACE at 30 days, defined as a composite of cardiovascular death, myocardial infarction or target vessel revascularisation. The primary effectiveness endpoint was procedural success which was defined as successful stent delivery with residual stenosis of <50%, and without in-hospital MACE.
“For those who think that is too low of a threshold there is also a secondary endpoint looking at residual stenosis of <30% without in-hospital MACE, as well as device crossing success and angiographic success,” said Price.
Of the total 384 patients, 191 had shorter lesions, while 190 patients presented with longer lesions. One patient lost to follow-up over time, so at 30 days there were 190 patients in both groups. Describing patient characteristics, Price commented that among those with longer lesions there was a preponderance of male patients, but otherwise described the two groups as “well balanced”.
In terms of angiographic lesion characteristics, Price said there were some modest differences between the two groups, but said that these were broadly in line with expectations. “Longer lesions tended to be more common in the right coronary artery, there was statistically significantly more calcified length and lesion length. By definition the longer group has longer lesions,” he said.
The average lesion length measured in the longer lesion group was 35.6mm, Price detailed, adding that calcified length was 54.9mm. “These are pretty horrific lesions,” he commented. “They are all severely calcified.”
Outlining the procedural characteristics Price explained that longer lesions took a longer time to treat. A larger number of stents were also used in the long lesion groups. However, he commented that there was no statistical difference in terms of the need for pre-dilatation, radial access, or post-stent dilatation in the two groups.
Turning to the outcomes, Price said that there were were no significant differences in final in-segment acute gain (1.4mm vs. 1.4mm, p=0.46), minimum lumen diameter (2.5mm vs. 2.5mm, p=0.74) or diameter stenosis (17.2mm vs. 18.3mm, p=0.25). Looking at angiographic complications, Price said that the most significant observations in the long lesion cohort were severe dissections in only 3% of procedures, which he said was statistically not significantly different than in those with shorter lesions, where it was seen in 2.3% of cases. “Overall,” he commented, “this is a very safe procedure”.
In terms of procedural success—the ability to deliver the stent with a residual stenosis <50% without in-hospital MACE—Price noted that no differences with long lesions versus short lesions (94.2% vs 99.5%, p=0.18). In the primary safety endpoint—freedom from 30-day MACE—Price and colleagues observed no difference in long lesions versus short lesions.
Closing his presentation, Price said: “The DISRUPT CAD III study long lesion cohort included a remarkably complex lesion subset, I would say one of the more complex lesion subsets ever studied in a prospective FDA registration study.
“Despite this complexity, IVL was associated with a statistically similar rate of the primary safety and effectiveness endpoints, compared with shorter lesions, similar procedural and device crossing success rates and 30-day MACE rates were numerically higher.”
This led to his concluding remark: “All in all, therefore, IVL is an attractive therapy to address severely calcified lesions across a spectrum of lesion length.”