Critical Limb Ischemia 2.0: Evolving Strategies To Boost Patient Outcomes

Simon Hogan, Senior Director of Medical Strategy at BTG International Inc.

There are mounting pressures today on healthcare stakeholders, including hospital administrators and clinicians, to control costs around disease prevention and management, while improving quality and patient outcomes. In this challenging environment, with multiple priorities competing for attention, undertreatment of complex diseases remains a constant challenge, often with devastating consequences. One example is the case of limb loss and the underlying medical conditions that can lead to it. Over two million people live with limb loss in the United States and every day, more than 500 Americans lose an upper or lower extremity.1 While there are many causes of limb loss, such as auto accidents or other injuries, a majority of amputations are due to peripheral vascular disease and diabetes, and can be prevented.1 The stakes are high: the number of people living without a limb is expected to double by 2050, if current trends are left unchecked.1

CLI is Growing in Prevalence

Critical limb ischemia (CLI) is the most advanced form of peripheral arterial disease (PAD) that currently impacts one in every 20 Americans over the age of 50, an incidence expected to increase with a growing aging population.2 CLI has been characterized as a “pathway to amputation”, since patients with this condition, a severe blockage of the arteries that reduces blood flow to the extremities, have an increased risk of major amputation, and face substantial morbidity and mortality risks.3 Diabetes is a common underlying condition of PAD and CLI, and is a rising epidemic in the U.S., with the fastest increases in senior citizens. A quarter of U.S. adults over the age of 65 years have diabetes and approximately half of those go undiagnosed.4 Smoking, high cholesterol, high blood pressure, sedentary lifestyle, and obesity are all also risk factors for PAD and CLI.

Patients, of course, benefit most from early diagnosis and medical treatment, but CLI can be complicated to detect, particularly in patients with other medical comorbidities. CLI, which won’t improve on its own, often results in a painful cycle of non-healing wounds due to skin ulcers, gangrene, and infection. Treatments for CLI include medications, endovascular therapies, and arterial surgery, with amputation considered the last recourse. But for a quarter of all newly diagnosed CLI patients, above- or below-the-knee amputation takes place within one year, coupled with the increased risk of amputation recurrence. At one year, 25% of patients will be dead, 30% will have undergone amputation, and only 45% will remain alive with both limbs.5 At five years, more than 60% of patients with critical limb ischemia will be dead, exceeding the five-year mortality rates for coronary artery disease, breast, and colon cancer.6

Evolving Therapies

These dire statistics have generated a wave of criticism from both advocacy groups and a new generation of practitioners, who maintain a large number of unnecessary primary amputations are taking place. Current imperatives to tackle this issue head on include a growing focus on the concept of limb salvage, with the goals to restore and maintain stability and ambulation through prevention strategies and new treatment approaches. A number of educational campaigns have been launched to promote public awareness about risk factors for amputation, such as the designation of an annual Limb Loss Awareness month by the Amputee Coalition and its Amplify Yourself initiative, seeking to raise awareness on gaps in appropriate medical care.

Developing safe and effective treatment modalities for CLI remains a central component to limiting the extent of amputation. Two trends in particular are impacting amputation prevention for the better and present new opportunities for clinicians, hospital administrators, and other health care stakeholders to both improve patient outcomes and stem healthcare costs related to amputation: advances in endovascular therapies, and the creation of limb salvage or preservation teams based on multidisciplinary care models that have proven successful in heart and cancer care.   

Endo-First

 A paradigm shift for CLI care has evolved over the past two decades, with a growing number of studies showing that endovascular therapy has overtaken surgical revascularization in CLI treatment7,8, generated by advances in endovascular surgical techniques and equipment. Multiple endovascular surgical technical strategies and skill sets necessary to treat CLI over the more traditional standard of care — open surgical bypass options — are increasingly documented in medical literature. These minimally invasive treatment interventions have been facilitated by the innovations in surgical equipment such as sheaths, guide catheters, microcatheters, scaffolds, balloons, stents, and procedures using clot-busting technologies and cross sectional and intravascular imaging, among others, and contributed to a growing prevalence of endovascular management of  CLI.9

Multiple studies have shown an endovascular approach has achieved acceptable success rates for CLI, resulting in lower mortality rates, shorter hospitals stays, and fewer amputations in study populations.10 But there are also downsides, including evidence that endovascular modalities have resulted in a higher need for reinterventions.11 As a result, many questions remain about optimal CLI treatment, complicated by the fact there are limited high quality data to guide practitioner decision making around an initial choice of surgical or endovascular strategies. These strategies can be most positively viewed as complementary, not competing strategies, and hybrid procedures combining both endovascular and open surgical techniques are evolving and show promise.11

Currently, the initial decision between surgical or endovascular interventions for CLI patients varies widely among practitioners and institutions, with many taking an “endo-first” strategy on the pretext the treatment is lower risk, which also appeals to patients.11 But research also shows that patients requiring open surgical revascularization following a failed endovascular procedure had a worse prognosis than those undergoing surgical revascularization as a first-line therapy.12 Providing rigorous data and clarity around “best endovascular” vs “best surgical” options for CLI patients eligible for both treatments are among the goals of the BEST-CLI randomized trial, now with over 140 centers in the U.S. and Canada participating, with over 1,300 patients.13 The trial, funded by the National Institutes of Health and scheduled to conclude next year, is focused not only on treatment efficacy, but functional outcomes, quality of life, and cost. Researchers anticipate that the trial results may fill the current gap in high quality data critical for practitioners to develop best practices around CLI care.

 Team Approach

Another innovation in CLI treatment has been the creation of collaborative limb salvage (or preservation) teams as a new standard of care, a concept catching on at growing numbers of hospitals around the country.14 These multidisciplinary teams typically include specialists from podiatry, wound care, vascular and endovascular surgery, plastic surgery, radiology, rheumatology, orthopedics, and emergency care, among others. The multidisciplinary approach provides a coordinated and comprehensive treatment protocol, allowing for more rapid assessment, management, and improved healing for patients. So far, multiple studies show that a team approach is effective in amputation prevention.14 For example, a study from researchers at Madigan Army Medical Center in Tacoma, Washington, tracking results after the initiation of a limb salvage team, found a 82% decrease in lower extremity amputations over a five-year period.15

At the Center for Limb Preservation established at the University of California San Francisco in 2011, researchers performed a one-year (2012-13) retrospective review of nearly 100 patients with neuro-ischemic wounds treated by its multidisciplinary amputation prevention team, specifically evaluating clinical endpoints of wound healing, re-ulceration rate, and ambulatory status. Results showed that wounds of over half of the study population fully healed by 12 weeks. There were only three primary amputations and 74% of patients were able to maintain or improve their ambulatory status, with an 11% reduction in hospital readmission rates in comparison to admissions for an all-inclusive population that underwent lower extremity revascularization at the institution. “Our data also suggest that a coordinated amputation prevention program may help to minimize hospital readmissions in this high-risk population,” UCSF researchers wrote.16 Such programs may also be catalysts for more research, clinical trials, and bench-to-bedside treatment innovations.

New Economics

Little data is available about the economic benefits of these two trends for CLI care. What’s clear is that the human toll and economic burden of amputation are considerable. Limb loss is a life-changing event that often results in reductions in a patient’s function, independence, and overall quality of life, and an increased incidence of depression, among other risks.14 Current research shows that fewer than two-thirds of patients with CLI who undergo primary amputation achieve success with a prosthesis.17 Limb amputation is a drain on both individual and healthcare resources. Prosthetic costs, for example, which are subject to much variation, are estimated to be upwards of $450,000 per person over a five-year period.18 Lifetime health care costs for a person with limb loss are upwards of $500,000, more than double the estimated lifetime health care costs of the average person, since amputees tend to be high utilizers of healthcare resources, including more frequent hospitalizations than patients with other chronic diseases.19 And these are conservative estimates, given that direct costs such as wheelchair accommodation or long-term assisted care due to primary amputation have yet to receive rigorous research scrutiny, as well as the many indirect costs that are difficult to measure such as job and productivity loss.

Available statistics paint a larger picture of the aggregate costs of amputation on national resources. Using data from the Centers for Medicare and Medicaid (CMS), the biggest national payer to amputee healthcare coverage, one study estimated (based on current trends) total lifetime direct healthcare costs for CMS services for the 73,000 CLI patients annually receiving lower extremity amputations at $46.7 billion.20 In comparison,  comprehensive limb salvage programs, according to the study, showed reduced rates of amputation ranging from 36% to 86%. Using those statistics to evaluate the impact of a hypothetical national limb salvation program, researchers estimated the new protocol could save CMS from $15.2 billion to $38.5 billion in the aggregate.

New care standards around limb salvage for CLI patients are likely to evolve in the near future, particularly due to the continuing advancement of endovascular surgical procedures and devices, and the adoption of team models to deliver care. These strategies deserve close evaluation by both clinicians and hospital administrators, since research suggests both increase the potential for more effective treatment and better outcomes for CLI patients. Also, all healthcare stakeholders should take note of these trends, given the growing emphasis on value-based healthcare, where providers are paid on patient outcomes. Amputation is one of the most expensive procedures in health care and one major study has documented it as the least cost-effective option compared to open surgical or “endo-first” management strategies in treating CLI patients with tissue loss.21 Current clinical trials are likely to generate similar evidence. Multidisciplinary limb salvage teams show promise in reducing long-term hospital costs, morbidity, and mortality for CLI patients, as well as contributing to their chances for maintaining a better quality of life.    

For clinicians and hospital administrators, a timely and efficient response to evolving CLI treatment modalities, with a focus on limb preservation for patients across multiple healthcare settings, should take high priority in an uncertain healthcare environment. Educating stakeholders, including patients and clinicians, and allocating the necessary resources to advance surgical techniques, treatments, and management of CLI are among measures to move forward and prevent misdiagnosis, unnecessary amputations, costly hospitals stays, and worse, untimely deaths.

 

References
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20. Palli S, Gunnarsson C, Kotlarz H, et al. Impact of a limb salvage program on the economic burden of amputation in the United States. Value in Health. 2016; 9(3): A45. Available online at https://doi.org/10.1016/j.jval.2016.03.098. Accessed December 21, 2018.

21. Barshes NR, Chambers JD, Cohen J, et al. Cost effectiveness in the contemporary management of critical limb ischemia with tissue loss. J Vasc Surgery. 2012; 56(4): 1015-1024.