Successful reperfusion of heavily calcified arteries often frustrates experienced operators using latest generation stent platforms, but investigators for the Disrupt CAD III trial reported that targeted intravascular lithotripsy can “safely and effectively” facilitate stenting of heavily calcified lesions.
Jonathan M. Hill, MD, of Royal Brompton Hospital in London, and colleagues reported their results in the Journal of the American College of Cardiology and co-investigator Dean Kereiakes, MD, of The Christ Hospital Heart and Vascular Center in Cincinnati, presented the results as a late-breaking clinical trial presentation at the Transcatheter Cardiovascular Therapeutics (TCT) virtual meeting.
The single-arm trial, which enrolled 431 patients at 47 clinical centers across 4 countries, was designed to gather data for regulatory approval of intravascular lithotripsy (IVL). “The primary safety endpoint was freedom from major adverse cardiovascular events (MACE: cardiac death, myocardial infarction or target vessel revascularization) at 30 days. The primary effectiveness endpoint was procedural success. Both endpoints were compared to a pre-specified performance goal (PG). The mechanism of calcium modification was assessed in an optical coherence tomography (OCT) sub-study,” Hill and colleagues wrote.
The pre-specified PG for safety was 84.4%, and at 30 days 92.2% of participants were free from MACE, and the “lower bound of the 95% confidence interval was 89.5%, which exceeded the PG of 84.4% (P <0.001),” they wrote. Likewise, the “primary effectiveness endpoint of procedural success was 92.4%; the lower bound of the 95% CI was 90.2% which exceeded the PG of 83.4% (P<0.0001).”
“MACE and target lesion failure (TLF) through 30 days occurred in 7.8% and 7.6% of patients, respectively, and was primarily driven by target vessel MI. There were 2 deaths (0.5%) within 30 days. One death occurred prior to hospital discharge (post-operative day [POD] 9) following emergency CABG required for abrupt coronary closure associated with a complicated and unsuccessful DES delivery. A second death occurred after discharge on POD 6 due to ST-segment elevation MI complicated by cardiogenic shock due to target vessel nontarget lesion thrombosis distal to the stent,” they wrote.
Additionally, 26 patients experienced peri-procedural MI.
“Stent thrombosis (ARC definite or probable) occurred in 3 (0.8%) patients within 30 days, on PODs 6, 7 and 21; all were associated with known predictors of stent thrombosis including stent under-expansion and mid-stent filling defect,” they added.
Likewise, the “primary effectiveness endpoint of procedural success was 92.4%; the lower bound of the 95% CI was 90.2% which exceeded the PG of 83.4% (P<0.0001).”
- Mean calcified segment length was 47.9±18.8 mm.
- Calcium angle was 292.5°±76.5°.
- Calcium thickness was 0.96±0.25 mm at the site of maximum calcification.
In his presentation Kereiakas noted that all lesions were graded “severely calcified by the core lab, and 30% had branch involvement.”
He noted that the results surpassed any that he had seen with other technology, although he noted that follow-up is needed to evaluate late outcomes.
In addition to meeting the safety and effectiveness endpoints, there were two other major findings from the trial, Hill and colleagues noted:
- “Transient IVL-induced left ventricular capture occurred frequently, but was benign with no lasting sequelae in any patient…
- “OCT demonstrated multi-plane and longitudinal calcium fractures after IVL in 67.4%of lesions, with excellent stent expansion in those with and without calcium fractures identified by OCT despite the marked severity of the calcified lesions treated.”
The authors noted that the study “had nearly identical enrollment criteria and endpoints as the predicate ORBIT II study of orbital atherectomy. Although Disrupt CAD III was not randomized, the PGs for the safety and effectiveness endpoints were based on those observed in ORBIT II which were superior to most prior studies in severely calcified lesions (thus minimizing the risk of non-inferiority creep). Both primary effectiveness and safety endpoints were met despite greater target lesion complexity in Disrupt CAD III compared with ORBIT II (e.g., mean lesion length 26.1 ± 11.7 mm versus 18.9 ± 8.4 mm, mean calcified length 47.9 ± 18.8 mm versus 28.6 ± 16.1mm). In this regard, the mean calcified segment length (47.9 ± 18.8 mm) by QCA, calcium angle (292.5° ± 76.5°) and thickness (0.96 ± 0.25 mm) at the site of maximum calcification by OCT represent the most severe target lesion calcification treated in any IDE study of calcium modification technology to date. Disrupt CAD III also confirms and extends prior observations from smaller studies (Disrupt CAD I, Disrupt CAD II) regarding the safety and effectiveness of IVL as an adjunct to coronary stent implantation despite a progressive increase in lesion complexity across studies.”
In addition to the non-randomized design of the trial, which is per se a limitation, the authors noted a number of other limitations, including the possibility that OCT may not “detect subtle morphologic changes in calcified plaque, the exclusion of adjunctive tools such as atherectomy that may facilitate IVL, and the exclusion of patients with “extremely tortuous vessels, true bifurcation lesions, and unprotected left main or ostial target lesions.” Taken together, those limitations may preclude the generalizability of the findings, they said.
Be aware that this report discusses safety and efficacy of a device that is not FDA approved.
The Disrupt CAD III trial found that IVL was safe and effective in a select group of patients with severely calcified lesions, but the trial excluded patients with extremely tortuous vessels.
Peggy Peck, Editor-in-Chief, BreakingMED™
The study was funded by Shockwave Medical, Inc.
Hill reported fees and grant support from Abbott Vascular, Boston Scientific, Abiomed, and Shockwave Medical and is a stockholder in Shockwave Medical.
Cat ID: 223
Topic ID: 74,223,223,306,308,925,222