Year : 2019 | Volume
: 6 | Issue : 3 | Page : 147--157
Global vascular guidelines on the management of chronic limb-threatening ischemia: A brief purview
Kalkunte R Suresh
Chief Editor – IJVES, Director – JIVAS, Bengaluru, Karnataka, India
Kalkunte R Suresh
Chief Editor – IJVES, Director – JIVAS, Bengaluru, Karnataka
|How to cite this article:|
Suresh KR. Global vascular guidelines on the management of chronic limb-threatening ischemia: A brief purview.Indian J Vasc Endovasc Surg 2019;6:147-157
|How to cite this URL:|
Suresh KR. Global vascular guidelines on the management of chronic limb-threatening ischemia: A brief purview. Indian J Vasc Endovasc Surg [serial online] 2019 [cited 2019 Nov 13 ];6:147-157
Available from: http://www.indjvascsurg.org/text.asp?2019/6/3/147/265780
The new paradigms detailed in Chapters 5 and 6 of this Document offer opportunities for clinical research, leading to the ratification of new staging system, its applications; new patient risk stratification PLAN, leading to Evidence-Based Revascularization (EBR). The vascular surgeons in India are inundated with patients with Critical Limb-Threatening Ischemia (CLTI) and nearly all with advanced, infected wounds. We, in India, perform several thousand open/endovascular procedures for CLTI and this opens up opportunities to find some answers to the research subjects tabulated at the end of these chapters. These are quoted at the beginning of this article to capture the attention of the readers. Perhaps, we can have registries or even better accumulate prospective clinical data to define/ratify the proposed staging and strategies.
The research areas suggested at the end of Chapter 5:
Chapter 6 on Strategies for Evidence Based Revascularization suggests the following “Research Priorities.”
Perhaps, the Vascular Society of India takes up some of these as pan India projects. Now, let us purview the Global Vascular Guidelines (GVG) on CLTI.
A comprehensive clinical practice guideline for the diagnosis and treatment of Critical Limb-Threatening Ischemia (CLTI replacing CLI), culmination of 5 years of efforts by nine steering committee members and 58 authors from 24 countries, was published as supplement to both JVS and EJVES in June 2019. The “Guidelines” attempts and succeeds in providing the vascular surgeons/specialists evidence-based document with consensus from vascular-related specialties, including vascular surgery, vascular medicine, interventional radiology and cardiology, angiology, and podiatry. The document should serve as the “Gold Standard” for the approach to CLTI across the world. Most of the contents of this article are extracted and quoted verbatim from this document., This brief does not replace the need to peruse the document in its entirety.
This is also the first document that considers global burden of the diseases and its approach across the world, recognizing:
Growing global prevalence of CLTI and risk factors, across high- and low-income countries High patient and public health costs Diverse specialties/providers and care settings Highly variable utilization of vascular interventions Wide disparity in outcomes, unclear standard of care Continuously evolving technology, shifting practice patterns Lack of consensus definitions and disease staging, a major limitation to the evidence-based medicine and clinical/outcomes research Define Key Research Questions and also involve global vascular surgeons/specialists in applying and ratifying important new classifications and suggested EBR And more importantly, Foster Improved Care and Quality Outcomes for these high-risk patients.
The entire document is presented in 13 sections, each with one or more lead authors and several coauthors from across the globe. This helps in understanding the demographics, epidemiology, and approach to CLTI in various continents and regions. The document has 680 references and nearly 120 recommendations. The chapters are listed below, and those which are at significant variance with current definitions are highlighted:
Definitions and nomenclature Global Epidemiology and risk factors for CLTI Diagnostic evaluation and limb staging of CLTI Medical management Anatomic staging – Global Limb Anatomical Staging System (GLASS) Strategies for Evidence-Based Revascularization (EBR) and PLAN Non-revascularization treatments of the limb Biologic and regenerative approaches Role of amputation Post-procedural care and surveillance Study designs and clinical trial endpoints Interdisciplinary team in CLTI Global perspectives and implementation
Definitions and Nomenclature: Chapter 1 of the Document
Defining and describing the severity of PAD
The term Critical Limb Ischemia (CLI) is out-dated and fails to encompass the full spectrum of patients who are evaluated and treated for limb-threatening ischemia in modern practice Instead, the term Chronic Limb-Threatening Ischemia (CLTI) is proposed, to include a broader and more heterogeneous group of patients with varying degrees of ischemia that can often delay wound healing and increase amputation risk. CLTI: spectrum of disease that includes patients with objectively documented PAD and any of the following:
Ischemic rest pain with confirmatory hemodynamic studies Diabetic foot ulcer Non-healing lower limb or foot ulceration of at least 2 weeks duration Gangrene involving any portion of the lower limb or foot Excluded: Patients with purely venous ulcers, acute limb ischemia, acute trash foot, ischemia due to emboli, acute trauma, and mangled extremity and those with wounds related to non-atherosclerotic conditions, such as vasculitis, collagen vascular disease, Buerger's disease, neoplastic disease, dermatoses, and radiation may have many underlying causes of their lower extremity disease and these are beyond the scope of these guidelines.
Diagnostic Evaluation: Chapter 3 from the Document
Clinical examination remains the mainstay of initial diagnosis, with noninvasive physiologic testing followed by duplex and CTA/MRA if needed. Catheter-based angiogram is not used as a diagnostic tool but used to define the anatomy after the need for intervention is established. The best medical therapy should be offered to all the patients, as described in Chapter 4 of the guidelines. The following flowchart outlines the diagnostic evaluation of the patient with CLTI.
Diagnostic Evaluation: Imaging – [Figure 3.2] from the document
Once the patient is deemed to be a candidate for revascularization, further evaluation to determine the anatomical pattern of the disease and the TAP (Target Artery Pathway)
Anatomic Staging – Global Limb Anatomical Staging System (Glass): Chapter 5 of the Document
Strategies for Evidence-Based Revascularization (Ebr) and Plan: Chapter 6 of the Document
NOTE: A limited discussion/outline is provided here, and the readers are encouraged to thoroughly read and understand these two chapters. The future issues of IJVES will detail these two important chapters of this document.
Patients with CLTI are at high risk for both limb and life loss. Limb salvage depends on effective revascularization of the threatened limb and this decision depends on multiple factors including patients' risk stratification, status of the limb, and anatomical pattern of the disease, which would lend itself to effective revascularization. There is limited high-quality evidence to support EBR and a new three-step integrated approach is suggested to facilitate decision-making in every day clinical practice and future research.
Patient Risk Limb threat severity: WIfI Staging (SVS-threatened limb classification) ANatomic pattern of disease: GLASS (Global Anatomical Staging System).
Structured Decision-Making in CLTI
P LAN: P atient risk estimation
CLTI is associated with advanced age, multiple comorbidities, and increased risks with revascularization without adequate preoperative assessment. Several tools for risk stratification are available as listed in [Table 6.1] of the document. Although majority of patients should be considered for limb saving revascularization, few may be better served with primary amputation or conservative management, after risk stratification. Those with expected perioperative mortality of >5% and <50% chance of 2-year survival are considered high risk, but this does not preclude revascularization. Others should be considered average risk.
P L AN: L imb threat severity
Staging of the limb is central to EBR. Complexity of wounds, severity of infection, and grades of ischemia dictate the outcomes of revascularization and chances of limb loss. Previous, existing classifications are inadequate to capture the full range of neuroischemic compromise, with various degrees of infections. SVS threatened limb classification system (WIfI) integrates all three parameters to stage CLTI. These are grouped into four stages based on estimated risk of limb loss and has been validated by several reports. This combined with GLASS and patient risk estimation provides a matrix to plan EBR.
PL AN : ANatomic pattern of the disease – GLASS (Global Anatomic Staging System)
Current anatomical classification systems focus of individual lesions (e.g., TASC) or overall burden of disease (e.g., Bollinger). However, they are not useful for defining EBR given the complexity, multilevel disease, increasing infra popliteal disease seen in patients with CLTI. Hence a clinically oriented framework for classifying the pattern of arterial disease in CLTI has been proposed. The GLASS is a fundamental departure from current approaches used in PAD and more analogous to the SYNTAX system for CAD.
Restoration of in-line pulsatile flow to the foot is the primary technical goal of revascularization in CLTI, by determining the Target Artery Path (TAP). The femoropopliteal and infrapopliteal diseases are graded (0–4), with progressively complex lesions. The CFA and proximal arteries are considered inflow arteries, and either they are disease-free or corrected; these are not part of GLASS.
The inframalleolar (pedal) diseases are graded as above but used only as a modifier and not part of main GLASS system.
Stage I: Low Complexity Disease
Expected technical failure <10% AND >70% 12-month Limb-Based Patency (LBP)
Stage II: Intermediate Complexity Disease
Expected technical failure <20% AND 12-month LBP 50%–70%
Stage III: High Complexity Disease
Expected technical failure >20%; OR <50% LBP
The above grades FP and IP are plotted on a grid, which assigns them to three stages of GLASS stages for the limb on TAP complexity score (for endovascular procedures).
The above flowchart illustrates the application of GLASS to stage infrainguinal disease pattern in CLTI [Figure 5.7] in the original document].
Global Perspectives and Implementation: Chapter 13 of the Document
The preceding sections of this guideline make recommendations regarding the diagnosis and treatment of CLTI based on data published in peer-reviewed journals and, where such data are lacking, consensus expert opinion. Vascular specialists managing CLTI across the globe serve the needs of diverse communities and cultures, working within a wide range of healthcare environments. Most vascular specialists will strive to keep up to date with the published evidence base and are greatly facilitated in doing so through the use of modern information technology systems. However, the reality is that most publications on CLTI are written in English, and the data contained therein overwhelmingly derive from relatively few countries, mainly high-income countries (HICs, Western Europe, North America, and Japan) that have mature, well-resourced health- and social-care systems, as well as clinical research infrastructure. Most vascular specialists treating patients with CLTI do not, of course, work in such favorable environments. As such, they often have to adapt foreign “evidence-based recommendations” to their own particular situation to provide the best possible care to their patients with the resources available. The GVG authors recognize this and, specifically, that some of the recommendations contained within this guideline are likely to remain aspirational for many vascular specialists working in diverse health care settings across the globe. The authors therefore thought it important to examine the state of CLTI care from a broader perspective. To that end, a questionnaire enquiring about the presentation, diagnosis, and management of CLTI was sent to vascular specialists (n = 50) working in a range of lower-, middle-, and higher-income countries. This section primarily comprises a description of the responses received (n = 22), supported by published loco-regional data where available.
Whereas the information provided may not be considered the highest quality from an epidemiologic perspective, a number of important global issues emerged from the responses. This brief overview highlights the urgent need for better data on the impact of CLTI and how it is managed around the world. The majority of responses derive from a few key opinion leaders from Latin America, Asia, and Africa; thus, the following discussion may not reflect concerns of other populations, providers, and nations.
Epidemiology and risk factors
Although accurate country-specific epidemiologic data are sparse, there seems little doubt that the increasing prevalence of DM, together with the growing use of tobacco and population aging is resulting in a significant increase in CLTI and amputations across much of the world, especially in LMICs (Low Middle Income Countries).
In 2013, Fowkes et al. undertook a meta-analysis of 34 studies to compare the prevalence and risk factors between HICs and LMICs. This is well outlined in Section 2 of this document, but it is worth recalling some of the key presented data. They concluded, “Globally, 202 million people were living with peripheral artery disease in 2010, 69.7% of them in LMIC, including 54.8 million in Southeast Asia and 45.9 million in the Western Pacific Region. During the preceding decade, the number of individuals with peripheral artery disease increased by 28.7% in LMIC and 13.1% in HIC. Also of note is the percentage of increase of PAD is higher in women than men in LMIC which is opposite of HIC.” The increase in PAD burden observed in women and in the younger, economically productive age groups is especially worrisome [Table 13.2].
The data on country-specific incidence of PAD and CLTI are sparse in these LMICs, unlike in HICs. There are no relevant epidemiologic data from large regions, but the updated data from Abbas are tabulated for perspective, reflecting PAD in diabetics in Sub-Saharan Africa [Table 13.3].
Lacking firm epidemiologic data, recent estimates of CLTI prevalence have used extrapolations from demographic and other available disease prevalence data, yielding global estimates of between 20 and 40 million individuals afflicted. About two-thirds of these are projected to be in LMICs. Unfortunately, documented data to support this are difficult to find in any indexed, peer-reviewed journals.
CLTI has a serious adverse economic impact on patients, their families, and wider communities right across the world but especially so in LMICs. Although these countries are often grouped together, the division between middle income and lower income is variable and imprecise. Furthermore, there is often considerable inequality within each LMIC, and respondents reported that most patients with CLTI (30%–90%) appear to come from poor socioeconomic backgrounds. The following data from the Indian National Sample Survey Office could represent the situation in many LMICs.
Only 18% of the urban population and 14% of rural population are covered by some form of health insurance Governmental health expenditure is <2% of gross domestic product overall. People in villages mainly depend on “household income or savings” (68%) and “borrowings” (25%) to fund hospitalization expenses Around 1% of the poor in rural areas have to sell their physical assets to meet health expenditure, and >5% seek help of friends and relatives. This is also in line with earlier studies showing that millions are pushed into poverty each year by medical expenditure and that such expenses are among the leading causes of indebtedness among the poor In cities, people rely much more on their income or savings (75%) than on borrowings (18%) to fund their treatment. Previous studies have repeatedly shown that India has one of the most privatized health care systems in the world, with out-of-pocket expenses accounting for the bulk of medical spending.
In India, the cost of IP bypass is U.S.$1500 to $3000, and costs of balloon angioplasty are similar. The use of a stent or DCB would add another U.S.$500 to $1000, and wound care adds at least U.S.$500. Such out-of-pocket expenses are probably unaffordable for most CLTI patients. Importantly, these costs depend on recycling of single-use devices such as sheaths, angioplasty balloons, and guide wires. Without such practice, the cost would increase by at least 50%, and far fewer patients, especially poorer ones, would have access to treatment, resulting in much greater loss of life and limb. Recycling of single-use devices (not just vascular devices) is common in Asia, Africa, Latin America, and Eastern Europe, and proper regulation of the practice, including appropriate consent procedures, is important to mitigate patient harm.
Summary of global perspectives
Based on the responses to the questionnaire and the limited published and unpublished data at times, we can draw the following conclusions.
CLTI is a significant and increasing global problem, especially in LMICs, where the incidence in women appears to be rising more quickly than in men Diabetes and unabated smoking are the major causes of CLTI globally Although vascular specialists try to follow the published evidence base, economic and social constraints mean that the approach to CLTI must to tailored to the working environment CLTI and diabetic foot problems are associated with high amputation rates in LMICs because of delayed presentation and referral and limited access to affordable care Economic constraints are an important limitation in the adoption of advanced vascular technologies and practical issues such as recycling of single-use devices require oversight from a public health perspective Few countries maintain national registries or other CLTI data sets Most countries do not have a standardized approach to CLTI, with considerable loco-regional variation in practice Most countries do not have well-organized and supported vascular societies where best practice and research can be shared and disseminated.
Dissemination and implementation
A large number of vascular specialists from around the world have contributed to the GVG, and that global involvement sets the present guideline document apart from all previous consensus statements. The paradigms and tools, such as WIfI, PLAN, and GLASS, set out in the GVG will, it is hoped, meet the needs of the global vascular community as expressed by our questionnaire respondents. However, some guideline recommendations will not be achievable by vascular specialists working in LMICs. The GVG recommendations should not, therefore, be viewed as an inflexible global “standard of care.” Following publication, it will be important to disseminate the GVG as quickly and widely as possible, simultaneously through a range of different channels, and to obtain validation and feedback from the global community. Dissemination will be assisted by publication of the full GVG as a supplement to the JVS and EJVES, publication of an executive summary with the recommendations in a range of other journals in a number of different languages, presentations at conferences, and free online access to the documents linked from societies' web pages.
As this guideline goes to press (April 2019), the safety of paclitaxel (PTX)-eluting devices for the treatment of PAD has come under intense scrutiny. The GVG Steering Committee, recognizing the importance of this issue to the vascular community, has unanimously approved the statement below. Given time constraints, this statement was not reviewed by the entire GVG Writing Group. This statement was approved by the three major sponsoring societies (ESVS, SVS, and WFVS).
Statement on the Safety of Paclitaxel-Eluting Devices for the Treatment of CLTI
Recently the safety of PTX-eluting devices for the treatment of patients with PAD has come into question. A meta-analysis of randomized controlled trials investigating these devices in the femoral and/or popliteal arteries identified increased mortality at two years and beyond in patients treated with the PTX devices versus controls. 680 These trials largely enrolled patients with intermittent claudication, with a small minority (11%) being within the spectrum of CLTI. Ongoing efforts from regulatory bodies and other independent groups seek to further clarify the validity of these observations. In the interim, the US Food and Drug Administration has urged caution in the use of PTX devices for treatment of PAD.
The GVG Steering Committee believes that the risks and benefits of treatments for CLTI, including drug-eluting devices, need to be examined with appropriately controlled, prospective studies that are specific to the CLTI population. In this regard, the execution of randomized controlled-trials involving PTX-eluting devices in CLTI, with appropriate safety monitoring and regulatory oversight, is important to the vascular community. Such trials should incorporate appropriate informed consent discussions with subjects, including the potential increased risk of mortality, and should mandate long-term follow-up for at least 2 years. Outside of such trials, given the indeterminate risk and efficacy of these devices in patients with CLTI, and the availability of alternative modalities, we believe that appropriate caution should be exercised.
GVG is a well-researched, updated document, which addresses various problems associated with CLTI across the globe and offers evidence-based approached which can indeed be practiced by vascular surgeons/specialists in all continents and regions. It also brings forth the much-needed system of classification and systems to facilitate EBR for both life and limb salvage. An app will be made available in the future to assist the practitioners to grade the patients with suggested in the document.
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