Management of Chronic Limb-Threatening Ischemia
Publication Date: June 3, 2019
Last Updated: December 15, 2022
Recommendations
Definitions and nomenclature
Use a lower extremity threatened limb classification staging system (eg, SVS’s WIfI classification system) that grades wound extent, degree of ischemia, and severity of infection to guide clinical management in all patients with suspected CLTI. ( S , C )
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Use objective hemodynamic tests to determine the presence and to quantify the severity of ischemia in all patients with suspected CLTI ( S , C )
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Global epidemiology and risk factors for CLTI
No recommendations (, )
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Diagnosis and limb staging in CLTI
Perform a detailed history to determine symptoms, past medical history, and cardiovascular risk factors in all patients with suspected CLTI (, )
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Perform a complete cardiovascular physical examination of all patients with suspected CLTI. (, )
GPS
681
Perform a complete examination of the foot, including an assessment of neuropathy and a probe-to-bone test of any open ulcers, in all patients with pedal tissue loss and suspected CLTI. (, )
GPS
681
Measure AP and ABI as the first-line noninvasive test in all patients with suspected CLTI. ( S , B )
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Measure TP and TBI in all patients with suspected CLTI and tissue loss (Fig 1). ( S , B )
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Consider using alternative methods for noninvasive assessment of perfusion, such as PVR, transcutaneous oximetry, or skin perfusion pressure, when ankle and toe pressures, indices, and waveforms cannot be assessed. ( W , C )
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Consider DUS imaging as the first arterial imaging modality in patients with suspected CLTI. ( W , B )
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Consider noninvasive vascular imaging modalities (DUS, CTA, MRA) when available before invasive catheter angiography in patients with suspected CLTI who are candidates for revascularization. ( W , B )
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Obtain high-quality angiographic imaging of the lower limb (with modalities and techniques to be determined by local available facilities and expertise). This should include the ankle and foot in all patients with suspected CLTI who are considered potential candidates for revascularization. (, )
GPS
681
Medical management
Evaluate cardiovascular risk factors in all patients with suspected CLTI. ( S , B )
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Manage all modifiable risk factors to recommended levels in all patients with suspected CLTI. ( S , B )
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Treat all patients with CLTI with an antiplatelet agent. ( S , A )
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Consider clopidogrel as the single antiplatelet agent of choice in patients with CLTI. ( W , B )
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Consider low-dose aspirin and rivaroxaban, 2.5 mg twice daily, to reduce adverse cardiovascular events and lower extremity ischemic events in patients with CLTI. ( W , B )
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Do NOT use systemic vitamin K antagonists for the treatment of lower extremity atherosclerosis in patients with CLTI. ( S , B )
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Use moderate- or high-intensity statin therapy to reduce all-cause and cardiovascular mortality in patients with CLTI. ( W , A )
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Control hypertension to target levels of <140 mm Hg systolic and <90 mm Hg diastolic in patients with CLTI. ( S , B )
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Consider control of type 2 DM in CLTI patients to achieve a hemoglobin A1c of <7% (53 mmol/mol [International Federation of Clinical Chemistry]). ( W , B )
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Use metformin as the primary hypoglycemic agent in patients with type 2 DM and CLTI. ( S , A )
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Consider withholding metformin immediately before and for 24–48 hours after the administration of an iodinated contrast agent for diabetic patients, especially those with an estimated glomerular filtration rate <30 mL/min/1.73 m2. ( W , C )
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Offer smoking cessation interventions (pharmacotherapy, counseling, or behavior modification therapy) to all patients with CLTI who smoke or use tobacco products. ( S , A )
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Ask all CLTI patients who are smokers or former smokers about status of tobacco use at every visit. ( S , A )
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Prescribe analgesics of appropriate strength for CLTI patients who have ischemic rest pain of the lower extremity and foot until pain resolves after revascularization. (, )
GPS
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In CLTI patients with chronic severe pain, use paracetamol (acetaminophen) in combination with opioids for pain control. (, )
GPS
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The GLASS for CLTI
Use an integrated, limb-based anatomic staging system (such as the GLASS) to define complexity of a preferred TAP and to facilitate EBR in patients with CLTI. (, )
GPS
681
Strategies for EBR
Refer all patients with suspected CLTI to a vascular specialist for consideration of limb salvage, unless major amputation is considered medically urgent. (, )
GPS
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Offer primary amputation or palliation to patients with limited life expectancy, poor functional status (eg, nonambulatory), or an unsalvageable limb after shared decision-making. (, )
GPS
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Estimate periprocedural risk and life expectancy in patients with CLTI who are candidates for revascularization. ( S , C )
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Define a CLTI patient as average surgical risk when anticipated periprocedural mortality is <5% and estimated 2-year survival is >50%. ( W , C )
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Define a CLTI patient as high surgical risk when anticipated periprocedural mortality is ≥5% OR estimated 2-year survival is ≤50%. ( W , C )
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Use an integrated threatened limb classification system (such as WIfI) to stage all CLTI patients who are candidates for limb salvage. ( S , C )
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Perform urgent surgical drainage and débridement (including minor amputation if needed) and commence antibiotic treatment in all patients with suspected CLTI who present with deep space foot infection or wet gangrene. (, )
GPS
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Repeat limb staging after surgical drainage, débridement, minor amputations, or correction of inflow disease (AI, common and deep femoral artery disease) and before the next major treatment decision. (, )
GPS
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Do NOT perform revascularization in the absence of significant ischemia (WIfI ischemia grade 0) unless an isolated region of poor perfusion in conjunction with major tissue loss (eg, WIfI wound grade 2 or 3) can be effectively targeted and the wound progresses or fails to reduce in size by ≥50% within 4 weeks despite appropriate infection control, wound care, and offloading. (, )
GPS
681
Do NOT perform revascularization in very-low–risk limbs (eg, WIfI stage 1) unless the wound progresses or fails to reduce in size by ≥50% within 4 weeks despite appropriate infection control, wound care, and offloading. ( W , C )
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Offer revascularization to all average-risk patients with advanced limb-threatening conditions (eg, WIfI stage 4) and significant perfusion deficits (eg, WIfI ischemia grades 2 and 3). ( S , C )
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Consider revascularization for average-risk patients with intermediate limb threat (eg, WIfI stages 2 and 3) and significant perfusion deficits (eg, WIfI ischemia grades 2 and 3). ( W , C )
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Consider revascularization in average-risk patients with advanced limb threat (eg, WIfI stage 4) and moderate ischemia (eg, WIfI ischemia grade 1). ( W , C )
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Consider revascularization in average-risk patients with intermediate limb threat (eg, WIfI stages 2 and 3) and moderate ischemia (eg, WIfI ischemia grade 1) if the wound progresses or fails to reduce in size by ≥50% within 4 weeks despite appropriate infection control, wound care, and offloading. ( W , C )
681
Obtain high-quality angiographic imaging with dedicated views of ankle and foot arteries to permit anatomic staging and procedural planning in all CLTI patients who are candidates for revascularization. (, )
GPS
681
Use an integrated limb-based staging system (eg, GLASS) to define the anatomic pattern of disease and preferred TAP in all CLTI patients who are candidates for revascularization. (, )
GPS
681
Perform ultrasound vein mapping when available in all CLTI patients who are candidates for surgical bypass. ( S , C )
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Map the ipsilateral GSV and small saphenous vein for planning of surgical bypass. Map veins in the contralateral leg and both arms if ipsilateral vein is insufficient or inadequate. (, )
GPS
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Do NOT classify a CLTI patient as being unsuitable for revascularization without review of adequate-quality imaging studies and clinical evaluation by a qualified vascular specialist. (, )
GPS
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Correct inflow disease first when both inflow and outflow disease are present in a patient with CLTI. (, )
GPS
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Base the decision for staged vs. combined inflow and outflow revascularization on patient risk and the severity of limb threat (eg, WIfI stage). ( S , C )
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Correct inflow disease alone in CLTI patients with multilevel disease and low-grade ischemia (eg, WIfI ischemia grade 1) or limited tissue loss (eg, WIfI wound grade 0/1) and in any circumstance in which the risk-benefit of additional outflow reconstruction is high or initially unclear. ( S , C )
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Restage the limb and repeat the hemodynamic assessment after performing inflow correction in CLTI patients with inflow and outflow disease. ( S , C )
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Consider simultaneous inflow and outflow revascularization in CLTI patients with a high limb risk (eg, WIfI stages 3 and 4), or in patients with severe ischemia (eg, WIfI ischemia grades 2 and 3). ( W , C )
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Use an endovascular-first approach for treatment of CLTI patients with moderate to severe (eg, GLASS stage IA) AI disease, depending on the history of prior intervention. ( S , B )
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Consider surgical reconstruction for the treatment of average-risk CLTI patients with extensive (eg, GLASS stage II) AI disease or after failed endovascular intervention. ( S , C )
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Perform open CFA endarterectomy with patch angioplasty, with or without extension into the PFA, in CLTI patients with hemodynamically significant (>50% stenosis) disease of the common and deep femoral arteries. ( S , C )
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Consider a hybrid procedure combining open CFA endarterectomy and endovascular treatment of AI disease with concomitant CFA involvement (GLASS stage IB). ( W , C )
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Consider endovascular treatment of significant CFA disease in selected patients who are deemed to be at high surgical risk or to have a hostile groin. ( W , C )
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Avoid stents in the CFA and do NOT place stents across the origin of a patent deep femoral artery. (, )
GPS
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Correct hemodynamically significant (≥50% stenosis) disease of the proximal deep femoral artery whenever technically feasible. (, )
GPS
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In average-risk CLTI patients with infrainguinal disease, base decisions of endovascular intervention vs. open surgical bypass on the severity of limb threat (eg, WIfI), the anatomic pattern of disease (eg, GLASS), and the availability of autologous vein. ( S , C )
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Offer endovascular revascularization when technically feasible for high-risk patients with advanced limb threat (eg, WIfI stage 4) and significant perfusion deficits (eg, WIfI ischemia grades 2 and 3). ( W , C )
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Consider endovascular revascularization for high-risk patients with intermediate limb threat (eg, WIfI stages 2 and 3) and significant perfusion deficits (eg, WIfI ischemia grades 2 and 3). ( W , C )
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Consider endovascular revascularization for high-risk patients with advanced limb threat (eg, WIfI stage 4) and moderate ischemia (eg, WIfI ischemia grade 1) if the wound progresses or fails to reduce in size by ≥50% within 4 weeks despite appropriate infection control, wound care, and offloading, when technically feasible. ( W , C )
681
Consider endovascular revascularization for high-risk patients with intermediate limb threat (eg, WIfI stages 2 and 3) and moderate ischemia (eg, WIfI ischemia grade 1) if the wound progresses or fails to reduce in size by ≥50% within 4 weeks despite appropriate infection control, wound care, and offloading, when technically feasible. ( W , C )
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Consider open surgery in selected high-risk patients with advanced limb threat (eg, WIfI stage 3 and 4), significant perfusion deficits (ischemia grade 2 or 3), and advanced complexity of disease (eg, GLASS stage III) or after prior failed endovascular attempts and unresolved symptoms of CLTI. ( W , C )
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Consider angiosome-guided revascularization in patients with significant wounds (eg, WIfI wound grades 3 and 4), particularly those involving the midfoot or hindfoot, and when the appropriate TAP is available. ( W , C )
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In treating FP disease in CLTI patients by endovascular means, consider adjuncts to balloon angioplasty (eg, stents, covered stents, or drug-eluting technologies) when there is a technically inadequate result or in the setting of advanced lesion complexity (eg, GLASSFP grade 2–4). ( W , B )
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Use autologous vein as the preferred conduit for infrainguinal bypass surgery in CLTI. ( S , B )
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Avoid using a nonautologous conduit for infrainguinal bypass unless there is no endovascular option and no adequate autologous vein. ( W , C )
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Perform intraoperative imaging (angiography, DUS, or both) on completion of open bypass surgery for CLTI and correct significant technical defects if feasible during the index operation. ( S , C )
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Nonrevascularization treatments of the limb
Consider SCS to reduce the risk of amputation and to decrease pain in carefully selected patients (eg, rest pain, minor tissue loss) in whom revascularization is not possible. ( W , B )
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Do NOT use LS for limb salvage in CLTI patients in whom revascularization is not possible. ( W , C )
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Consider IPC therapy in carefully selected patients (eg, rest pain, minor tissue loss) in whom revascularization is not possible. ( W , B )
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Do NOT offer prostanoids for limb salvage in CLTI patients. Consider offering selectively for patients with rest pain or minor tissue loss and in whom revascularization is not possible. ( W , B )
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Do NOT offer vasoactive drugs or defibrinating agents (ancrod) in patients in whom revascularization is not possible. ( S , C )
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Do NOT offer HBOT to improve limb salvage in CLTI patients with ischemic ulcers in whom revascularization is not possible. ( S , A )
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Continue to provide optimal wound care until the lower extremity wound is completely healed or the patient undergoes amputation. (, )
GPS
681
Biologic and regenerative medicine approaches in CLTI
Restrict use of therapeutic angiogenesis to CLTI patients who are enrolled in a registered clinical trial. ( S , B )
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The role of minor and major amputations
Consider transmetatarsal amputation of the forefoot in CLTI patients who would require more than two digital ray amputations to resolve distal necrosis, especially when the hallux is involved. ( W , C )
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Offer primary amputation to CLTI patients who have a pre-existing dysfunctional or unsalvageable limb, a poor functional status (eg, bedridden), or a short life expectancy after shared decision-making with the patient and health care team. ( S , C )
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Consider secondary amputation for patients with CLTI who have a failed or ineffective reconstruction and in whom no further revascularization is possible and who have incapacitating pain, nonhealing wounds, or uncontrolled sepsis in the affected limb after shared decision-making with the patient and health care team. ( W , C )
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Consider revascularization to improve the possibility of healing an amputation at a more distal functional amputation level (eg, AKA to BKA), particularly for patients with a high likelihood of rehabilitation and continued ambulation. ( W , C )
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Consider a TKA or AKA in patients who are nonambulatory for reasons other than CLTI (ie, bedridden patients with flexion contracture, dense hemiplegia, cancer) and are unlikely to undergo successful rehabilitation to ambulation. ( W , C )
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Involve a multidisciplinary rehabilitation team from the time a decision to amputate has been made until successful completion of rehabilitation has been achieved. ( S , C )
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Continue to observe CLTI patients who have undergone amputation at least yearly to monitor progression of disease in the contralateral limb and to maintain optimal medical therapy and risk factor management. ( S , C )
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Postprocedural care and surveillance after infrainguinal revascularization for CLTI
Continue best medical therapy for PAD, including the long-term use of antiplatelet and statin therapies, in all patients who have undergone lower extremity revascularization. ( S , A )
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Promote smoking cessation in all CLTI patients who have undergone lower extremity revascularization. ( S , A )
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Consider DAPT (aspirin plus clopidogrel) in patients who have undergone infrainguinal prosthetic bypass for CLTI for a period of 6–24 months to maintain graft patency. ( W , B )
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Consider DAPT (aspirin plus clopidogrel) in patients who have undergone infrainguinal endovascular interventions for CLTI for ≥1 month. ( W , C )
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Consider DAPT for 1–6 months in patients undergoing repeated catheter-based interventions if they are at low risk for bleeding. ( W , C )
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Observe patients who have undergone lower extremity vein bypass for CLTI on a regular basis for ≥2 years with a clinical surveillance program consisting of interval history, pulse examination, and measurement of resting APs and TPs. Consider DUS scanning where available. (, )
GPS
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Observe patients who have undergone lower extremity prosthetic bypass for CLTI on a regular basis for ≥2 years with interval history, pulse examination, and measurement of resting APs and TPs. (, )
GPS
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Observe patients who have undergone infrainguinal endovascular interventions for CLTI in a surveillance program that includes clinical visits, pulse examination, and noninvasive testing (resting APs and TPs). (, )
GPS
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Consider performing additional imaging in patients with lower extremity vein grafts who have a decrease in ABI ≥0.15 and recurrence of symptoms or change in pulse status to detect vein graft stenosis. (, )
GPS
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Offer intervention for DUS-detected vein graft lesions with an associated PSV of >300 cm/s and a PSV ratio >3.5 or grafts with low velocity (midgraft PSV <45 cm/s) to maintain patency. ( S , B )
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Maintain long-term surveillance after surgical or catheter-based revision of a vein graft, including DUS graft scanning where available, to detect recurrent graft-threatening lesions. ( S , B )
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Consider arterial imaging after endovascular intervention for failure to improve (wound healing, rest pain) or a recurrence of symptoms to detect restenosis or progression of pre-existing disease. ( W , C )
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Consider reintervention for patients with DUS-detected restenosis lesions >70% (PSV ratio >3.5, PSV >300 cm/s) if symptoms of CLTI are unresolved or on a selective basis in asymptomatic patients after catheter-based interventions. ( W , C )
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Provide mechanical offloading as a primary component for care of all CLTI patients with pedal wounds. ( S , A )
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Provide counseling on continued protection of the healed wound and foot to include appropriate shoes, insoles, and monitoring of inflammation. ( S , A )
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Study designs and trial end points in CLTI
Use a research framework such as the IDEAL for gathering new data and evidence on the surgical and endovascular management of CLTI (GRS) (, )
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Encourage funders, journal reviewers, and editors to prioritize prospective, multicenter, controlled, and preferably randomized studies over retrospective case series, studies using historical controls, or other less rigorous research methodologies.(GRS) (, )
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When RCTs are not feasible, use the OPG benchmarks from the SVS’s Critical Limb Ischemia Working Group to evaluate the efficacy of novel endovascular CLTI techniques and devices.(GRS) (, )
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To facilitate sufficient enrollment, limit RCT exclusion criteria to those who are deemed essential to trial integrity. (GRS) (, )
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Design RCTs, prospective cohort studies, and registries that are specific to CLTI. (GRS) (, )
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Use an integrated, limb-based threatened limb classification system (eg, WIfI) and a whole limb anatomic classification scheme (eg, GLASS) to describe the characteristics and outcomes of CLTI patients who are enrolled. (GRS) (, )
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Describe outcomes in CLTI trials using a combination of objective and clinically relevant events, subjective PROMs and HRQL assessments, and anatomic and hemodynamic end points. (GRS) (, )
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Require regulatory trials aimed at obtaining premarket approval for devices for use in CLTI to study CLTI patients and to present data on objective and clinically relevant end points, PROMs and HRQL assessments, and anatomic and hemodynamic end points. (GRS) (, )
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Follow up patients in trials for a time sufficient (this will usually be >2 years) to allow appropriate comparison of the impact of the different interventions on the natural history of CLTI. Measure and declare completeness of follow-up coverage to quantify risk of attrition bias. (GRS) (, )
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Include a time-integrated measure of clinical disease severity (such as freedom from CLTI) in the CLTI trial design to describe the total impact of comparator CLTI interventions. (GRS) (, )
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Publish all CLTI trial protocols together with the full statistical analysis plans in peer-reviewed journals to allow independent, public, and transparent scrutiny and to prevent nonreporting of negative trials. (GRS) (, )
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Conduct postmarketing surveillance data collection using well-designed, large observational studies and registries. (GRS) (, )
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Share clinical trial data to allow subsequent individual patient data analyses, meta-analyses, and subgroup analyses; updating of OPGs; and validation of decision-making tools, such as the WIfI system and GLASS. (GRS) (, )
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Assess the quality of evidence in CLTI research using frameworks such as GRADE that consider multiple certainty domains and are not based solely on study design. (GRS) (, )
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Recommendation Grading
Overview
Title
Management of Chronic Limb-Threatening Ischemia
Authoring Organization
Society for Vascular Surgery
Endorsing Organizations
American Podiatric Medical Association
Society of Interventional Radiology
Publication Month/Year
June 3, 2019
Last Updated Month/Year
December 19, 2024
Supplemental Implementation Tools
Document Type
Guideline
External Publication Status
Published
Country of Publication
US
Document Objectives
Chronic limb-threatening ischemia (CLTI) is associated with mortality, amputation, and impaired quality of life. These Global Vascular Guidelines (GVG) are focused on definition, evaluation, and management of CLTI with the goals of improving evidence-based care and highlighting critical research needs. The term CLTI is preferred over critical limb ischemia, as the latter implies threshold values of impaired perfusion rather than a continuum.
Target Patient Population
Patients with Chronic limb-threatening ischemia (CLTI)
PICO Questions
Is there evidence that other measures, such as outflow bed resistance or below-knee runoff scores, are predictive of procedural or clinical outcomes? How do these compare with target path lesion complexity assessed by angiography?
Is there a simple, reproducible method for quantification of calcification that has predictive value for infrainguinal interventions?
Are there specific patient factors (eg, demographic or comorbidity) associated with anatomic patterns of disease in CLTI?
Are there anatomic patterns of disease in which an endovascular approach is futile?
How does lesion morphology (eg, concentric vs eccentric) influence treatment success for different endovascular interventions?
Is there a correlation between GLASS stage and clinical presentation (WIfI)?
What is the comparative value of direct (angiosome based) vs indirect revascularization in the setting of tissue loss, and how should it drive selection of the preferred TAP? Is this specific to wound location or WIfI stage? Open table in a new tab
Inclusion Criteria
Male, Female, Adult, Older adult
Health Care Settings
Ambulatory, Hospital, Outpatient, Radiology services, Operating and recovery room
Intended Users
Nurse, nurse practitioner, physical therapist, physician, physician assistant, podiatrist
Scope
Diagnosis, Treatment, Management
Diseases/Conditions (MeSH)
D058729 - Peripheral Arterial Disease
Keywords
peripheral artery disease (P.A.D.), PAD, critical limb ischemia, CLTI, Peripheral artery disease, chronic limb threatening ischemia, foot ulcer
Supplemental Methodology Resources
Systematic Review Document, Systematic Review Document, Systematic Review Document, Systematic Review Document