The Fast-Evolving Field of Drug-Coated Balloons in Below-the-Knee Disease

Disclosures: 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.

In times where we feel as if the answer to drug-coated balloon (DCB) use below the knee (BTK) is just around the corner, new pieces of the puzzle fall out of place. The good news is, we do have the pieces for the puzzle and eventually, we will be able to put it together. However, the question that remains is, when will we have this done? There are so many questions that remain to be answered. The goal is to bind old and new technologies, both pharmacological and mechanical, to finally find the Holy Grail for BTK disease. Dr. Granada will share his thoughts and experiences with us regarding the fast-evolving field of DCB BTK therapy. 

J.A. Mustapha, MD: When you consider below-the-knee (BTK) disease, do you automatically compare the anatomy to that of the coronaries?

Juan F. Granada, MD: Not really. BTK lesions contain different biological and pathological substrates, including differences in calcium, lipid content, and plaque burden, compared to the coronary vessels. Disease burden in the BTK vessels (including fundamental differences in lesion length) makes this environment quite complex compared to coronary artery disease.

J. Mustapha: Do you believe there is a difference in vessel wall reaction to drug-coated balloons (DCB) between above-the-knee (ATK) versus BTK disease? 

J. Granada: I think the overall cellular-level reaction to anti-proliferative drugs is comparable. However, the biological makeup of each vascular territory determines the biological effect and prevention of restenosis induced by these agents. It all comes down to the capacity each local drug delivery device has in sustaining therapeutic tissue levels over time in a predictable fashion.

J. Mustapha: Do you see the current trend of DCB therapy for BTK disease as a positive or a negative trend?

J. Granada: Neutral trend, I would say. We know DCB are safe and effective in the superficial femoral artery (SFA) territory. However, the real role of DCB for BTK applications remains to be proven. We are hopeful emerging drug delivery technologies will unlock the field of BTK intervention. 

J. Mustapha: Do you believe we have what we need to get diseased BTK vessels under control or is something missing?

J. Granada: The field of BTK intervention is still in its infancy. However, the field of local drug delivery is rapidly evolving and providing exciting therapeutic options for the future. I feel though that we need to be careful, as the basis of disease is not completely understood and additional basic knowledge in this area is still needed. However, I think that other more sophisticated ways to deliver drugs could potentially be required in this complex vascular territory. It is just still too early to predict who will develop the best technology for the complex BTK territory.  

J. Mustapha: There are many DCB excipients. Do you have a preference, and if so, why?

J. Granada: I don’t have any personal preferences. Each excipient is used in the DCB manufacturing to serve specific technical purposes. Although some show technological advantages today, they may become antiquated in the years to come. It is still too early to determine which one of the available excipients has the most acceptable performance profile in BTK applications.

J. Mustapha: Does atherectomy make sense scientifically in terms of de-bulking prior to treating a high plaque burden vessel with DCB?

J. Granada: I am not sure we have enough scientific data to support this approach. However, intuitively it makes sense, as de-bulking plaque to facilitate drug delivery is appealing. However, more clinical data in a large group of patients is needed to validate this clinical approach. In any case, physicians will continue using this approach, since in some clinical situations, the technical requirements of the procedures overcome the fact clinical data is limited.   

J. Mustapha: Recoil in BTK vessels is known to affect acute luminal gain. Would a specially designed BTK stent make a difference in reducing BTK recoil, hence improving acute luminal gain post-DCB?

J. Granada: This is a biological factor that is a matter of intense debate. Some believe that scaffolding is the best approach. Others believe that only partial scaffolding or no scaffolding is more appropriate. It is still too early in this debate to determine the winning approach in complex BTK intervention. However, in a high plaque burden state, especially in the presence of calcium, the scaffolding effect may prove to be beneficial.

J. Mustapha: Mid to distal tibial vessels are notorious for high compression force, making most of the currently available stents obsolete. Is there anything on the horizon for these segments of the tibial vessels?

J. Granada: At the present time, there is not a dedicated device to use in this vascular territory. However, medical technology today has the ability to develop unique, low-profile, durable devices for these particular applications. In the future, I am hopeful that new technologies, possibly based on smart nano-materials and manufacturing processes, will provide us options for advanced tibial disease.

J. Mustapha: Is it fair to say we have covered reasonable advances in the treatment of BTK, but still have a long way to go? If yes, how much longer until we reach adequate therapies for BTK disease?

J. Granada: I think that the introduction of local drug delivery for peripheral vascular disease intervention has created an opportunity to treat BTK disease. We are just at the beginning of a new era, and I am sure we will start seeing the introduction of new devices and therapeutic options. I believe we have a bright and exciting future in front of us.  New technologies are before us that will be disruptive for this field of complex BTK disease that urgently requires new options.