One-year outcomes from the Disrupt CAD III clinical study of Shockwave intravascular lithotripsy (IVL) have shown low rates of major adverse cardiovascular events (MACE) and target lesion failure, demonstrating a “sustained and persistent relative benefit” of IVL for lesion preparation prior to coronary stenting, according to investigators.
The latest data release from Disrupt CAD III were released in one of several presentations at the Transcatheter Cardiovascular Therapeutics annual meeting (TCT 2021, 4–6 November, Orlando USA and virtual) to document the use of IVL. Further to this a gender analysis that found similar outcomes between men and women, and an OCT analysis that found consistent acute performance in eccentric, concentric and nodular calcified lesions.
According to investigators, the low rate of MACE (13.8%) seen in the first one-year outcomes from the prospective, multicentre, single-arm, global investigational device exemption (IDE) Disrupt CAD III study were primarily driven by the rate of non-Q wave myocardial infarction (9.2%), demonstrating durable safety and effectiveness following lesion preparation with IVL prior to stent deployment. The MACE rate included low rates of cardiac death (1.1%), myocardial infarction (10.5%), and target vessel revascularisation (6%) one year after the index procedure.
The study also demonstrated a low rate of target lesion failure (11.9%), while target lesion revascularisation (TLR), occurred in only 4.3% of patients and definite or probable stent thrombosis occurred in 1.1% of patients at one year, with only one patient having a definite or probable stent thrombosis beyond 30 days, resulting a late stent thrombosis rate of at 0.3%.
“It is very significant that these data show sustained and persistent relative benefit of IVL for lesion preparation prior to coronary stenting, particularly since this is the first robust one-year report that has been presented on the technology,” said Dean Kereiakes medical director of The Christ Hospital Heart and Vascular Center and the Christ Hospital Research Institute; Professor of Clinical Medicine, The Ohio State University (Columbus, USA), co-principal investigator of Disrupt CAD III. “The achievement of an average stent expansion of 102% and a minimum stent area (MSA) of 6.5mm2 at the index procedure with IVL should have predicted excellent long-term results. We were optimistic that there should be a low rate of late target lesion revascularisation and stent thrombosis to one year, and that is exactly what we found following IVL.”
A pooled analysis of 262 patients enrolled in OCT sub-studies from Disrupt CAD I, II, III, and IV, the largest intravascular imaging analysis of any calcium modification tool to date, confirmed that coronary IVL achieved excellent MSA and stent expansion (SE) consistently in lesions with both eccentric and concentric calcium. MSA and SE at the maximum site of calcification were similar across the four calcium arc quartiles analysed: ≤180 degrees (6.1mm2 and 104%), 181‒270 degrees (6mm2 and 101%), 271‒359 degrees (6.1mm2 and 98%) and 360° (6.2mm2 and 105%), respectively.
In a separate analysis of calcific nodules, coronary IVL was found to have a notable acute effect on calcific nodules, which were identified in 22% of cases, either by flattening or fracturing the nodule, resulting in consistent MSA (6.3mm2 vs. 6mm2) and SE (101% vs. 103%) in lesions with calcified nodules (n=54) or those without (n=194), respectively. The analysis also found that calcific nodules, defined as an accumulation of nodular calcification, or small calcium deposits, with disruption of fibrous cap on the calcified plate, were more commonly associated with concentric calcium and greater overall calcium burden.
“The ability to modify calcium regardless of its morphology, whether eccentric, concentric or nodular, and have MSA and stent expansion still remain consistent shows the versatility of IVL to make a meaningful impact on clinical practice,” said Ziad Ali, director of the DeMatteis Cardiovascular Institute and Investigational Interventional Cardiology at St Francis Hospital & Heart Center, New York, USA and presenter of the data at TCT. “To date all OCT analyses of IVL reveal that the greater the calcium burden, the greater the number of fractures. These data now show that evidence of visible fracture by OCT is not necessary to achieve large MSA or adequate stent expansion, particularly in these unique, but clinically relevant sub-groups of calcification. The take home message is that IVL liberates vascular compliance in all sub-groups including eccentric lesions and calcified nodules.”
A pooled analysis of the Disrupt CAD I, II, III, and IV studies showed IVL was equally safe and effective in men and women, unlike previous findings with atherectomy. The analysis of 628 patients stratified outcomes by sex. Women in the analysis, who accounted for 23% of total patients, were older and more likely to have hyperlipidemia, renal insufficiency and prior myocardial infarction. Despite more frequent comorbidities and smaller vessel size in women, the primary safety endpoint of 30-day MACE for women and men was similar (8.3% vs 7.1%, p=0.61). The primary effectiveness endpoint of procedural success for women and men was also similar (91.7% vs 92.6%, p=0.72). Notably, there were also consistent post-IVL serious angiographic complications between women and men (1.6% vs 2.3%, p=0.75), which differs from previous atherectomy gender analyses.
“Given the strong safety profile of IVL and the known higher risks of women undergoing PCI, coronary IVL is an attractive option for optimising outcomes in female patients,” said Alexandra Lansky, director of Yale Cardiovascular Clinical Research Program Yale University School of Medicine, New Haven, USA. “While this is the first analysis of its kind for coronary IVL, it is highly suggestive that the technology could potentially serve as first-line therapy for women with calcified lesions, particularly if these findings can be confirmed in a larger patient cohort.”
Summarising the totality of the data presented at TCT 2021, Kereiakes, commented: “Looking at these data holistically, it does not matter whether you are in Europe, Japan or the USA It does not matter if you are in a big centre, or little centre. It does not matter which type of calcium or which type of patients you are treating. The beauty of these data are the consistency of safety and effectiveness. We found no differences with IVL. For these reasons I call IVL the great equaliser.”
