An Overview of CLI Therapies

Disclosure: Dr. Mustapha reports he is a consultant to Bard Peripheral Vascular, Covidien, Cordis, CSI, Spectranetics, and Boston Scientific.

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

Introducing a new, monthly column for CLD readers, headed by section editor J.A. Mustapha, MD, Metro Health Hospital, Wyoming, Michigan.

Dr. Mustapha shares his perspective on available therapies for critical limb ischemia and his plans for upcoming columns.

Critical limb ischemia (CLI) is a complex entity, and is best described as the chaotic expression of the atherosclerotic process affecting the arterial circulation of the lower limbs. Despite the fact that well-described risk factors are known to eventually determine the future outcome of peripheral artery disease, small individual variations or factors can widely alter the timeline of disease progression through the different stages of severity, affecting different patients in different ways, in a non-predictable pattern.  

CLI patients typically present with multivessel and multi-level disease, spanning from the origin of the aorto-iliac junction, through the superficial, profunda femoral, and popliteal arteries, traversing all the way to the tibial and pedal circulation. If we stop to think about these elements for a minute, and consider the plethora of data points to be interpreted when simply describing the vasculature tree alone, one cannot help but wonder about the overwhelming magnitude and depth of clinical evaluation, non-invasive testing, invasive evaluation, and multiple forms of revascularization (including both open and closed), that should be carried and considered when facing a CLI patient. In this era, the trend toward minimally invasive approaches is fast and furious. Accrued data is favoring an “endovascular-first” strategy and there is a constant flow of innovations being added to the toolbox of the endovascular interventionist. This phenomenon has been fueled in part by the clever shift toward lower profile access tools and support catheters, coupled to an ever-growing array of low-profile, high-torque, high-push, and high gram tip wires, that are used alone or in combination to improve the ability to cross complex chronic total occlusions (CTOs). Currently, there are multiple CTO crossing devices available in the market. Some are designed to accommodate the complexity and severity of the multiple types of CTO caps found in CLI lesions. Supporting catheters have also simultaneously evolved, moving through two complementary paths. First was the development of low-profile catheters that have made a significant difference in CTO crossing, wire support, wire exchange (both above and below the knee), and, more recently, have allowed for the performance of below-the-ankle CLI therapy. Second, these catheters were turned into truly torqueable tools, associated with excellent trackability, pushability, and much-improved supporting shafts, making these catheters less likely to kink.

Once lesions are crossed, they still need to be treated. Although stents have been available for many years, they have been used primarily in superficial femoral artery (SFA) and popliteal lesions with acceptable results. To meet the need for additional stent features that could overcome the aggressive nature of the disease state today, stent elements have been forced to evolve more dynamically in order to support the high burden of severely calcified plaque typically seen in CLI patients. Balloon-expandable drug-eluting stents (DES) thrived in the proximal tibial arteries after release of the PARADISE, YUKON, ACHILLES and DESTINY studies, with intermediate and mixed results in the mid tibial arteries, and failure in the distal tibial and pedal arteries. These findings left a significant unmet need in a key anatomical stretch that stands today without a go-to treatment tool. This column will trigger many discussions about CLI’s unmet treatment needs over the course of the upcoming year. Key opinion leaders from across the globe will be interviewed to bring readers up to date on the latest therapeutic options for CLI therapy.

Balloons for CLI therapy are becoming more important than ever as a front-line therapy in the battle against CLI. Fortunately, evolution continues to be the norm in technological advances related to balloon manufacturing, and has led to low-profile balloons that can cross very tight and long CTO segments.  These segments require low-profile balloons with tracking shafts that also add pushability. These combined features allow balloons to traverse long, high-grade stenotic lesions with high calcium burden and CTOs. However, there was still a need for an additional power source to push against the calcified plaque with robust and concise force in order to dilate the lesion without harming the vessel, which led to the development of multiple scoring and specialty balloons.  

Despite these significant advancements, operators still find themselves in situations where the resistant nature of the plaque fails to yield to the balloon method in general. Addressing yet another obstacle in the path of CLI therapy, atherectomy was developed to address complex lesions resisting other interventional strategies. Interestingly, atherectomy has also evolved into a tool that can treat all spectrums of CLI plaque, from hyperplastic non-calcified lesions to the most obstructive, severely calcified lesions. This forum will provide stimulating discussions over the course of the next 12 months on up-to-date technical aspects of all the atherectomy devices on the market. In addition to sharing tips and tricks related to atherectomy, international clinical data will be made available to guide device selection based on multiple additive factors. No two lesions are ever the same; therefore, treatment approaches must be modified to accommodate the lesion and the patient. To accommodate the challenging reality of CLI lesions, operators must assess each lesion to choose an atherectomy device that will provide the best result when coupled with the specific lesion’s morphology and patient attributes. Different concepts of atherectomy will be reviewed, including plaque modification, debulking (with directional atherectomy), aspiration and debulking combined therapy, thermal ablation, central debulking, and debulking by microcavitation.

Last, but definitely not least, future columns will be devoted to the discussion of the latest addition to the U.S. endovascular interventionist’s toolbox, drug-coated balloons (DCBs). The arrival of DCBs to the United States to treat above-the-knee vessels is yet another step forward in the evolution of therapies for CLI. Globally, there have been a few small trials and single-center experiences combining DCB with atherectomy, DCB with stenting, and DCB to treat in-stent restenosis. This column will explore the U.S. usage of the DCB, both alone and in combination with other technologies as they unfold.   

The goal is to establish a sequential, algorithmic discussion on how to best utilize each of the currently available tools to halt the progression of the chaotic CLI state, which continues to advance and confound the currently available therapeutic modalities. Innovative technologies and the recently emerging field of bio-nanotechnologies, coupled with ever-improving operator skills and understanding of CLI, give promise to a future where the tables will be turned and the disease defeated, leading to a definite down-sloping curve in the plot of amputation rates due to CLI. A shift must occur and therapies must progress in order to contribute to better outcomes for patients and avoid the high morbidity and mortality rate associated with limb loss.  
Studying the intense complexity and chaos typical of the CLI state also elicits questions about the organization and delivery of therapies. Are we heading toward CLI centers of excellence, solely dedicated to this highly complex disease state? Can a singular vascular specialist treat CLI? Or are we heading toward an era of multiple vascular specialists working under the same umbrella? At this point, we must continue to push forward and wait for the future to show us the answer. In the meantime, keep on treating CLI.