The Emerging Young Field of CLI Holds Great Potential

Introduction

J.A. Mustapha, MD

Critical limb ischemia (CLI) and its multi-level, multi-vessel disease encompasses any of the infrainguinal arteries. Over the last few years, we have seen a great deal of discussion on how to address tibial-pedal disease. In this issue, we are shifting gears to address inflow for the CLI patient and discuss primarily superficial femoral artery (SFA) and popliteal issues. Over the last two years, we have seen a great deal of new, positive, and encouraging data on the SFA and some new data on the popliteal. Successful inflow therapy for CLI is necessary to decrease the historic restenosis rates that cause many endovascular procedures to be prohibitive. 

In this issue, I am honored to interview Juan F. Granada, MD. Dr. Granada is the Executive Director and Chief Innovation Officer of the CRF Skirball Center for Innovation. He is also an Assistant Professor of Medicine at Columbia University College of Physicians and Surgeons. Dr. Granada is one of the world’s foremost investigators in the evaluation of emerging cardiovascular technologies. He is also a co-director of Transcatheter Cardiovascular Therapeutics (TCT), the annual scientific symposium of the Cardiovascular Research Foundation (CRF) and world’s largest educational meeting specializing in interventional cardiovascular medicine. This year’s meeting will take place October 29-November 2, 2016 in Washington, D.C. TCT has created an encompassing peripheral vascular session that includes discussions on inflow disease state.

J.A. Mustapha, MD: Dr. Granada, TCT has brought to us much of the coronary data that we use in our practice on a daily basis. When and what prompted CRF to add peripheral vascular intervention to a meeting historically known for its cardiac focus?

Juan F. Granada, MD: Peripheral vascular disease (PVD) is the fastest growing specialty in endovascular therapies today. In recent years, the local drug delivery wave has started to rapidly migrate into PVD territory. We have started to see improvements in clinical outcomes with the use of these devices, energizing the field by promoting further clinical research and investment in innovation. So I think what is coming in the next decade in PVD intervention is very exciting. At TCT, we always look for ways to enhance the program with whatever is new and relevant, so naturally, PVD has to be a centerpiece of the meeting. Also, because there is the large amount of overlap between clinical specialists, especially in the United States, a program tailored for the needs of the interventional cardiologist is extremely relevant.

Dr. Mustapha: With recent drug-coated balloon (DCB) trials showing positive outcomes, do you believe this is the peak of SFA/popliteal treatment or do you envision many more treatment options to come?

Dr. Granada: No, not at all. I think the most amazing thing that has happened with DCB to date is that we have essentially seen feasibility and success of local drug delivery. We have now proven that the delivery of paclitaxel via balloon technologies improves clinical outcomes over plain old balloon angioplasty (POBA).  Following this initial success, the way has been paved for new technologies to be developed. I am particularly excited about the new generation DCBs, the use of alternative drugs, and also the development of innovative and more sophisticated drug delivery mechanisms. This is just the beginning; the fun is about to start!

Dr. Mustapha: Is the cycle we are seeing of plain old balloon angioplasty (POBA) to stents to drug-eluting stents (DES) to DCB in the SFA/popliteal similar to the coronary cycle?

Dr. Granada: Even though we have learned important lessons in the development of coronary technologies, we should not try to generalize those lessons into the development of PV technologies. I do believe, though, that the field of PV interventions is going to develop in a similar way to coronary technologies. Future randomized, head-to-head comparative studies are needed to truly understand the superiority of one technology over the other. Future clinical adoption of these technologies is going to be based on evidence-based medicine and data. Due to the differences in anatomical substrates, technical approaches, and the way clinical trials are designed in the PV space, clinical development and technology adoption will likely be different. But, at the end of the day, industry will be obliged to generate a solid clinical foundation to show the potential clinical benefit of their technologies. The era of single-arm studies using historical controls is definitely over.

Dr. Mustapha: What do attendees expect to see this year at TCT regarding infrainguinal PV therapy?

Dr. Granada: We have been working with leaders in the field to introduce PVD intervention sessions at TCT.  We always have a full-blown session on DCB and local drug delivery for the SFA, and try to include dedicated sessions on below-the-knee interventions as well. This year is not going to be any different. However, we have emerging data on different applications and uses of different technologies.  I think we should continue strengthening those sessions by bringing more thought-provoking topics on these specific fields.

Dr. Mustapha: Do you foresee a future where SFA/popliteal surgical bypass will remain at the same rate, or do you predict an increase or decrease in its use?

Dr. Granada: I think it is difficult to really say what the future is going to unveil. But there is a strong trend in every single area of cardiovascular medicine toward the use of less invasive methods and toward more minimally invasive approaches. One thing I do know is that catheters will become easier to use, smaller in size, and more sophisticated, facilitating the delivery of therapies and rapid recovery of patients. I do believe endovascular, minimally invasive techniques will continue to develop very rapidly and at some point, they will overtake the development of surgical techniques. Now the only way to prove superiority is to conduct comparative, randomized, controlled trials. I predict the pace of development of endovascular, minimally invasive techniques will be much faster than any other improvement in surgical techniques. I do believe that sometime in the future (I don’t know how long it will take), minimally invasive catheter techniques could potentially become the mainstay of therapy.

Dr. Mustapha: What are “must-see” sessions for the cardiologist coming to TCT for the first time this year? 

Dr. Granada: TCT is structured in such a way that we combine live cases, teaching demonstrations, and didactic sessions. The live case demonstrations occur in the morning and focus on clinical indications, techniques, and device application, while the mainstream data download occurs in the afternoon during the didactic sessions. TCT has a very rich program that covers all areas, from coronary care to structural heart disease and PV interventions. There will be many sessions focused on providing a comprehensive review of the applicability of available clinical data into daily clinical practice. Also, we have an exciting innovation program that takes place in the morning for those that are interested in new and emerging technologies. It is a fun and refreshing program for attendees that are interested in future technologies on the horizon.

Dr. Mustapha: Dr. Granada, thank you for the pre-clinical work you have done that has led to many of the currently available tools for use during treatment of the SFA/popliteal. You continue to be very involved in delivering crucial data that acts as the driving force behind newer and more effective technologies. Will any sessions at TCT 2016 discuss and showcase preclinical work?

Dr. Granada: Yes. TCT aims to deliver a message based on science and evidence-based medicine. We believe that clinical outcomes are only improved if technologies are properly validated through well-designed clinical studies and most importantly, with solid science behind the technologies. Throughout the meeting, we have a fair amount of experimental validation studies that are presented primarily in the innovation sessions. If you look at the program, the beginning of each session usually contains a few talks aiming to describe the science and relevant translational aspects of the technologies presented in each session. 

Dr. Mustapha: You have been very involved with drug-eluting stents and balloons. What do you say to our readers in regard to tibial disease and the two failed DCB trials?

Dr. Granada: Honestly, it is too early to make any final conclusions in regard to the use of DCBs for below-the-knee indications/application. This is a field that is extremely complex and has more confounding variables than any other field we are currently involved with. It comes down not only to the anatomical issues, but also to the wide variety of techniques used, population involved, and study design used to validate these technologies. Also, post intervention care is as important as the treatment itself. We have to be very careful when it comes down to the validation of device performance in this challenging field. For sure, the data available is intriguing and clinical results are not as clear as the ones seen in the SFA territory. However, we must admit that emerging technologies are rapidly evolving and could make a positive impact in this particular clinical application. The local drug delivery field is stronger than ever and new technologies are being developed at a very fast pace. I am sure that in the near future, we will have plenty of new technologies available with the potential to improve clinical outcome in this complex field. The evolution of this field is critical, because the level of a patient’s disability and subsequent health care spending is just too big to be neglected. I hope this field grows very, very fast for the sake of our patients’ health and wellbeing.

Dr. Mustapha: What are your thoughts on atherectomy followed with DCB in the tibials based on your preclinical experience?

Dr. Granada: The use of atherectomy in peripheral vascular interventions preceding drug delivery makes logical sense. It still needs to be proven in large, randomized, controlled studies. The fact that you can actually debulk a large amount of complex atherosclerotic tissue in a highly diseased vessel may enhance drug uptake and allow for better drug distribution. Also, the fact that you could potentially decrease dependence on the use of stents makes it particularly attractive. It is still early, but a handful of small clinical studies show this approach is feasible. However, like everything in our field, properly sized, randomized studies need to be done to prove this approach is safe and effective before adoption by the scientific community and regulatory agencies occurs. This is yet another exciting growth opportunity that could be impactful in the future. 

Disclosure: Dr. Mustapha reports he is a consultant for Bard, Covidien, Cordis, CSI, Spectranetics, Boston Scientific, Cook, and Terumo. Dr. Juan Granada reports that the Skirball Center for Innovation has received research grants from companies involved in the development of peripheral vascular disease technologies.

Dr. J.A. Mustapha can be contacted at jihad.mustapha@metrogr.org.

Dr. Juan Granada can be contacted at jgranada@crf.org.