A Systematic Review of Cost-Utility Analyses in Chronic Limb-Threatening Ischemia


      To review and describe the available literature on cost-utility analysis of revascularization and non-revascularization treatment approaches in chronic limb-threatening ischemia.


      A systematic review was performed on cost-utility analysis studies evaluating revascularization (open surgery or endovascular), major lower extremity amputation, or conservative management in adult chronic limb-threatening ischemia patients. Six bibliographic databases and online registries were searched for English language articles up to August 2021. The outcome for cost-utility analysis was quality-adjusted in life years. Procedures were compared using incremental cost-effectiveness ratios which were converted to 2021 United States dollars. Study reporting quality was assessed using the 2022 Consolidated Health Economic Evaluation Reporting Standards statement. The study was registered in International Prospective Register of Systematic Reviews (CRD42021273602).


      Three trial-based and five model-based studies were included for review. Studies met between 14/28 and 20/28 criteria of the Consolidated Health Economic Evaluation Reporting Standards CHEERS statement. Only one study was written according to standardized reporting guidelines. Most studies evaluated infrainguinal disease, and adopted a health care provider perspective. There was a large variation in the incremental cost-effectiveness ratios presented across studies. Open surgical revascularization (incremental cost-effectiveness ratios: $3,678, $58,828, and $72,937), endovascular revascularization (incremental cost-effectiveness ratios: $52,036, $125,329, and $149,123), and mixed open or endovascular revascularization (incremental cost-effectiveness ratio: $8,094) maybe more cost-effective than conservative management.


      The application of cost-utility analyses in chronic limb-threatening ischemia is in its infancy. Revascularization in infrainguinal disease may be favored over major lower extremity amputation or conservative management. However, data is inadequate to support recommendations for a specific treatment. This review identifies short and long-term considerations to address the current state of evidence. Cost-utility analysis is an important tool in healthcare policy and should be encouraged amongst the vascular surgical community.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Annals of Vascular Surgery
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Duff S.
        • Mafilios M.S.
        • Bhounsule P.
        • et al.
        The burden of critical limb ischemia: a review of recent literature.
        Vasc Health Risk Manag. 2019; 15: 187-208
        • Song P.
        • Rudan D.
        • Zhu Y.
        • et al.
        Global, regional, and national prevalence and risk factors for peripheral artery disease in 2015: an updated systematic review and analysis.
        Lancet Glob Health. 2019; 7: e1020-e1030
        • Conte M.S.
        • Bradbury A.W.
        • Kolh P.
        • et al.
        Global vascular guidelines on the management of chronic limb-threatening ischemia.
        J Vasc Surg. 2019; 69: 03S-125S.e40
        • Mustapha J.A.
        • Katzen B.T.
        • Neville R.F.
        • et al.
        Determinants of long-term outcomes and costs in the management of critical limb ischemia: a population-based cohort study.
        J Am Heart Assoc. 2018; 7: e009724
        • Moriarty J.P.
        • Murad M.H.
        • Shah N.D.
        • et al.
        A systematic review of lower extremity arterial revascularization economic analyses.
        J Vasc Surg. 2011; 54: 1131-1144.e1
        • Javidan A.P.
        • Naji F.
        • Li A.
        • et al.
        A systematic review of economic evaluations in vascular surgery.
        Ann Vasc Surg. 2020; 67: 511-520.e1
        • Vissapragada R.
        • Bulamu N.
        • Karnon J.
        • et al.
        Cost-effectiveness in surgery: concepts of cost-utility analysis explained.
        ANZ J Surg. 2021; 91: 1717-1723
        • Guyatt G.H.
        • Ferrans C.E.
        • Halyard M.Y.
        • et al.
        Exploration of the value of health-related quality-of-life information from clinical research and into clinical practice.
        Mayo Clin Proc. 2007; 82: 1229-1239
        • Drummond M.
        • Sculpher M.J.
        • Claxton K.
        • et al.
        Methods for the economic evaluation of health care programmes. 4th ed.
        Oxford University Press, Oxford2015
        • Almasri J.
        • Adusumalli J.
        • Asi N.
        • et al.
        A systematic review and meta-analysis of revascularization outcomes of infrainguinal chronic limb-threatening ischemia.
        J Vasc Surg. 2018; 68: 624-633
        • Soga Y.
        • Iida O.
        • Takahara M.
        • et al.
        Two-year life expectancy in patients with critical limb ischemia.
        JACC Cardiovasc Interv. 2014; 7: 1444-1449
        • van Reijen N.S.
        • Hensing T.
        • Santema T.K.B.
        • et al.
        Outcomes of conservative treatment in patients with chronic limb threatening ischaemia: a systematic review and meta-analysis.
        Eur J Vasc Endovasc Surg. 2021; 62: 214-224
        • Page M.J.
        • McKenzie J.E.
        • Bossuyt P.M.
        • et al.
        The PRISMA 2020 statement: an updated guideline for reporting systematic reviews.
        BMJ. 2021; 372: n71
        • van Mastrigt G.A.
        • Hiligsmann M.
        • Arts J.J.
        • et al.
        How to prepare a systematic review of economic evaluations for informing evidence-based healthcare decisions: a five-step approach (part 1/3).
        Expert Rev Pharmacoecon Outcomes Res. 2016; 16: 689-704
        • Arber M.
        • Glanville J.
        • Isojarvi J.
        • et al.
        Which databases should be used to identify studies for systematic reviews of economic evaluations?.
        Int J Technol Assess Health Care. 2018; 34: 547-554
        • Husereau D.
        • Drummond M.
        • Augustovski F.
        • et al.
        Consolidated health economic evaluation reporting standards (CHEERS) 2022 explanation and elaboration: a report of the ISPOR CHEERS II good practices task force.
        Value Health. 2022; 25: 10-31
      1. Campbell and cochrane economics methods group and the evidence for policy and practice information and coordinating centre. Cost converter.
        (Available from:)
        Date: 2021
        Date accessed: August 1, 2021
        • Barshes N.R.
        • Chambers J.D.
        • Cohen J.
        • et al.
        Cost-effectiveness in the contemporary management of critical limb ischemia with tissue loss.
        J Vasc Surg. 2012; 56: 1015-1024.e1
        • Bradbury A.W.
        • Adam D.J.
        • Bell J.
        • et al.
        Multicentre randomised controlled trial of the clinical and cost-effectiveness of a bypass-surgery-first versus a balloon-angioplasty-first revascularisation strategy for severe limb ischaemia due to infrainguinal disease. The bypass versus angioplasty in severe ischaemia of the leg (BASIL) trial.
        Health Technol Assess. 2010; 14 (iii-iv): 1-210
        • Brothers T.E.
        • Rios G.A.
        • Robison J.G.
        • et al.
        Justification of intervention for limb-threatening ischemia: a surgical decision analysis.
        Cardiovasc Surg. 1999; 7: 62-69
        • Forbes J.F.
        • Adam D.J.
        • Bell J.
        • et al.
        Bypass versus angioplasty in severe ischaemia of the leg (BASIL) trial: health-related quality of life outcomes, resource utilization, and cost-effectiveness analysis.
        J Vasc Surg. 2010; 51: 43S-51S
        • Hunink M.G.
        • Wong J.B.
        • Donaldson M.C.
        • et al.
        Revascularization for femoropopliteal disease. A decision and cost-effectiveness analysis.
        J Am Med Assoc. 1995; 274: 165-171
        • Kearns B.C.
        • Michaels J.A.
        • Stevenson M.D.
        • et al.
        Cost-effectiveness analysis of enhancements to angioplasty for infrainguinal arterial disease.
        Br J Surg. 2013; 100: 1180-1188
        • Peters C.M.L.
        • de Vries J.
        • Redeker S.
        • et al.
        Cost-effectiveness of the treatments for critical limb ischemia in the elderly population.
        J Vasc Surg. 2019; 70: 530-538.e1
        • Villemoes M.K.
        • Lindholt J.S.
        • Houlind K.C.
        • et al.
        Cost-effectiveness evaluation of heparin coated versus standard graft for bypass surgery in peripheral artery disease alongside a randomised controlled trial.
        Eur J Vasc Endovasc Surg. 2018; 56: 87-93
        • Kuntz K.
        • Sainfort F.
        • Butler M.
        • et al.
        Decision and simulation modeling in systematic reviews. 2013.
        (Available from:)
        Date: 2021
        Date accessed: October 7, 2021
        • Mustapha J.A.
        • Katzen B.T.
        • Neville R.F.
        • et al.
        Disease burden and clinical outcomes following initial diagnosis of critical limb ischemia in the Medicare population.
        JACC Cardiovasc Interv. 2018; 11: 1011-1012
        • Jonsson B.
        Ten arguments for a societal perspective in the economic evaluation of medical innovations.
        Eur J Health Econ. 2009; 10: 357-359
        • Byford S.
        • Raftery J.
        Perspectives in economic evaluation.
        BMJ. 1998; 316: 1529-1530
        • Goodrich K.
        • Kaambwa B.
        • Al-Janabi H.
        The inclusion of informal care in applied economic evaluation: a review.
        Value Health. 2012; 15: 975-981
        • Simons J.P.
        • Goodney P.P.
        • Nolan B.W.
        • et al.
        Failure to achieve clinical improvement despite graft patency in patients undergoing infrainguinal lower extremity bypass for critical limb ischemia.
        J Vasc Surg. 2010; 51: 1419-1424
        • Smith A.D.
        • Hawkins A.T.
        • Schaumeier M.J.
        • et al.
        Predictors of major amputation despite patent bypass grafts.
        J Vasc Surg. 2016; 63: 1279-1288
        • Mustapha J.A.
        • Anose B.M.
        • Martinsen B.J.
        • et al.
        Lower extremity revascularization via endovascular and surgical approaches: a systematic review with emphasis on combined inflow and outflow revascularization.
        SAGE Open Med. 2020; 8 (2050312120929239)
        • Shields G.E.
        • Wilberforce M.
        • Clarkson P.
        • et al.
        Factors limiting subgroup Analysis in cost-effectiveness analysis and a call for transparency.
        Pharmacoeconomics. 2022; 40: 1-8
        • Parvar S.L.
        • Thiyagarajah A.
        • Nerlekar N.
        • et al.
        A systematic review and meta-analysis of gender differences in long-term mortality and cardiovascular events in peripheral artery disease.
        J Vasc Surg. 2021; 73: 1456-1465.e7
        • Billig J.I.
        • Sears E.D.
        • Travis B.N.
        • et al.
        Patient-reported outcomes: understanding surgical efficacy and quality from the patient's perspective.
        Ann Surg Oncol. 2020; 27: 56-64
        • Porter M.
        • Teisberg E.
        Redefining Health Care: creating value-based competition on results.
        Harvard Business School Press, Boston, Massachusets2006
        • Porter M.E.
        • Larsson S.
        • Lee T.H.
        Standardizing patient outcomes measurement.
        N Engl J Med. 2016; 374: 504-506
        • Porter M.E.
        What is value in health care?.
        N Engl J Med. 2010; 363: 2477-2481
        • Porter M.
        Value-based healthcare.
        (Available from:)
        • Shan L.
        • Shi M.
        • Tew M.
        • et al.
        Measuring quality of life in chronic limb-threatening ischemia patients and informal carers: a scoping review.
        Ann Surg. 2022; (In press)
        • Morrison A.
        • Polisena J.
        • Husereau D.
        • et al.
        The effect of English-language restriction on systematic review-based meta-analyses: a systematic review of empirical studies.
        Int J Technol Assess Health Care. 2012; 28: 138-144