We had the privilege of connecting with Dr. Robert Riley Director, Complex Coronary Therapeutics Program, The Christ Hospital Health System. Dr. Riley is the leading author of the abstract for the Patient-Level Pooled Analysis of the DISRUPT CAD I, II, III and IV studies and presented at ACC.21 Virtual.
Read the JACC publication and enjoy the Q&A:
Why did we conduct a pooled analysis of the DISRUPT CAD I, II, III and IV studies?
Dr. Robert Riley: When evaluating coronary IVL as a treatment modality, it was really important to not only look at the data from initial studies but to also combine these studies into a pooled analysis in order to increase the statistical power to look at the clinical endpoints. This pooled analysis represents the largest analysis of coronary IVL to date and showed consistency of the results across differing patient groups and operators and should assure people who are getting started with coronary IVL as to the safety and efficacy of the technology.
What makes these studies eligible for a pooled analysis?
Dr. Robert Riley: The DISRUPT CAD I, II, III and IV studies had uniform study criteria endpoints, adjudication and follow up. They had the same safety and effectiveness endpoints. This is really important because it allowed us to pool the data. It also allowed us to conduct multivariate and subgroup analyses that have a higher degree of statistical validity when you have the same study criteria, endpoints, & adjudication criteria.
How would you describe the baseline demographics of patients included in this analysis?
Dr. Robert Riley: This analysis included a patient group with a higher preponderance of risk factors that are known to be associated with not only coronary artery disease, but specifically calcified coronary disease. Over half of the patients smoked, there was a high prevalence of diabetes, dyslipidemia, hypertension, the patients were older with an average age of 71.8 years, and a quarter of patients had renal insufficiency. This is a really high-risk cohort which gives us confidence in using this technology to treat patients we see in the cath lab everyday.
We see that bifurcation lesions, prior MI and long lesion length were predictors of MACE and lower procedural success. Are these data what you expected, and can you help put these data into context?
Dr. Robert Riley: If you look at recent studies or trials evaluating most stent or calcium treatment modalities, these are the same predictors that consistently show up. One of the shortcomings we still have with PCI that we have to remember is that when we percutaneously treat coronary disease, we are often only treating a single spot in the vessel. So, when we have longer lesions and more complex lesions like bifurcations and patients with prior MI, we know they are already at higher risk for future events, regardless of how the current lesion is treated.
Furthermore, in the CAD pooled analysis, more than 80% of the in-hospital and 30-day MACE were driven mainly by NQWMI. Per protocol, we measured CK-MB levels after these procedures even though the majority of these patients wouldn’t get these enzyme levels measured after the procedure unless there is a clinical reason, but in order to do cross comparison with other calcium modification strategies, the measurements and endpoints needed to be similar. There are thresholds with which these enzyme levels being elevated after procedure do correlate with poor outcomes, but there is also a lot of debate as to what that cutoff should be.
From your perspective, what are the key takeaways from this publication?
Dr. Robert Riley: The biggest takeaway is that this is the largest assessment to date of coronary IVL and we show that there are excellent safety profiles and treatment effectiveness in a very complex lesion cohort. The other takeaway is that these outcomes were consistent across different countries, patient populations and user experience. We also know that it’s consistent with prior studies, which gives us a lot of confidence that this is a very effective & safe treatment modality for very complex, calcified lesions.
What can interventional cardiologists expect next from the DISRUPT CAD clinical program?
Dr. Robert Riley: I think what we are going to see first and foremost is maturation of the algorithms for how to treat calcium. IVL isn’t the only modality to treat calcium and a lot of these technologies are going to be complimentary. I think we will see a big emphasis on how imaging will drive what type of technology are we going to use in each case, along with how to define an effective outcome (i.e. when a calcified vessel is properly prepared for stenting). Then, I think we will see a maturation of the technology use in different types of calcium, how are we going to use it in longer lesions, etc. Now that we have proven the safety and effectiveness of the technology, we can start having fun with how we use it and learn how to continue to improve the effectiveness of the therapy and our ability to discriminate when to use it. The sky is really the limit as we start to learn how to use IVL in bifurcations, left mains, longer lesions and all sorts of different kinds of things coming down the pipe.
Dr. Robert Riley is a paid consultant for Shockwave Medical.
Coronary Important Safety Information:
In the United States: Rx only.
Indications for Use—The Shockwave Intravascular Lithotripsy (IVL) System with the Shockwave C2 Coronary IVL Catheter is indicated for lithotripsy-enabled, low-pressure balloon dilatation of severely calcified, stenotic de novo coronary arteries prior to stenting.
Contraindications—The Shockwave C2 Coronary IVL System is contraindicated for the following: This device is not intended for stent delivery. This device is not intended for use in carotid or cerebrovascular arteries.
Warnings— Use the IVL Generator in accordance with recommended settings as stated in the Operator’s Manual. The risk of a dissection or perforation is increased in severely calcified lesions undergoing percutaneous treatment, including IVL. Appropriate provisional interventions should be readily available. Balloon loss of pressure was associated with a numerical increase in dissection which was not statistically significant and was not associated with MACE. Analysis indicates calcium length is a predictor of dissection and balloon loss of pressure. IVL generates mechanical pulses which may cause atrial or ventricular capture in bradycardic patients. In patients with implantable pacemakers and defibrillators, the asynchronous capture may interact with the sensing capabilities. Monitoring of the electrocardiographic rhythm and continuous arterial pressure during IVL treatment is required. In the event of clinically significant hemodynamic effects, temporarily cease delivery of IVL therapy.
Precautions— Only to be used by physicians trained in angiography and intravascular coronary procedures. Use only the recommended balloon inflation medium. Hydrophilic coating to be wet only with normal saline or water and care must be taken with sharp objects to avoid damage to the hydrophilic coating. Appropriate anticoagulant therapy should be administered by the physician. Precaution should be taken when treating patients with previous stenting within 5mm of target lesion.
Potential adverse effects consistent with standard based cardiac interventions include– Abrupt vessel closure – Allergic reaction to contrast medium, anticoagulant and/or antithrombotic therapy-Aneurysm-Arrhythmia-Arteriovenous fistula-Bleeding complications-Cardiac tamponade or pericardial effusion-Cardiopulmonary arrest-Cerebrovascular accident (CVA)-Coronary artery/vessel occlusion, perforation, rupture or dissection-Coronary artery spasm-Death-Emboli (air, tissue, thrombus or atherosclerotic emboli)-Emergency or non-emergency coronary artery bypass surgery-Emergency or non-emergency percutaneous coronary intervention-Entry site complications-Fracture of the guide wire or failure/malfunction of any component of the device that may or may not lead to device embolism, dissection, serious injury or surgical intervention-Hematoma at the vascular access site(s)-Hemorrhage-Hypertension/Hypotension-Infection/sepsis/fever-Myocardial Infarction-Myocardial Ischemia or unstable angina-Pain-Peripheral Ischemia-Pseudoaneurysm-Renal failure/insufficiency-Restenosis of the treated coronary artery leading to revascularization-Shock/pulmonary edema-Slow flow, no reflow, or abrupt closure of coronary artery-Stroke-Thrombus-Vessel closure, abrupt-Vessel injury requiring surgical repair-Vessel dissection, perforation, rupture, or spasm. Risks identified as related to the device and its use: Allergic/immunologic reaction to the catheter material(s) or coating-Device malfunction, failure, or balloon loss of pressure leading to device embolism, dissection, serious injury or surgical intervention-Atrial or ventricular extrasystole-Atrial or ventricular capture.
Prior to use, please reference the Instructions for Use for more information on warnings, precautions and adverse events. https://shockwavemedical.com/IFU
Please contact your local Shockwave representative for specific country availability and refer to the Shockwave C2 instructions for use containing important safety information.
