Authors' objectives: Chronic limb-threatening ischaemia with ischaemic pain and/or tissue loss. To examine the clinical and cost-effectiveness of a vein bypass-first compared to a best endovascular treatment-first revascularisation strategy in preventing major amputation or death. Chronic limb-threatening ischaemia (CLTI) is the severest manifestation of peripheral arterial disease (PAD) and presents with ischaemic pain at rest or tissue loss (ulceration, gangrene or both) or both. The researchers compared the effectiveness of a vein bypass (VB)-first with a best endovascular treatment (BET)-first revascularisation strategy in terms of preventing major amputation and death in patients with CLTI who required an infra-popliteal (IP) revascularisation, with or without an additional more proximal infra-inguinal revascularisation procedure, to restore limb perfusion. The primary objective of the study was to examine the effectiveness and cost-effectiveness of using a VB-first compared to a BET-first revascularisation strategy in terms of preventing major (above the ankle) amputation or death from any cause [amputation-free survival (AFS)] in patients with CLTI who required an IP, with or without an additional more proximal infra-inguinal revascularisation procedure, to restore limb perfusion.

Authors' results and conclusions: Between 22 July 2014 and 30 November 2020, 345 participants were randomised, 172 to vein bypass-first and 173 to best endovascular treatment-first. Non-amputation-free survival occurred in 108 (63%) of 172 patients in the vein bypass-first group and 92 (53%) of 173 patients in the best endovascular treatment-first group [adjusted hazard ratio 1.35 (95% confidence interval 1.02 to 1.80); p = 0.037]. Ninety-one (53%) of 172 patients in the vein bypass-first group and 77 (45%) of 173 patients in the best endovascular treatment-first group died [adjusted hazard ratio 1.37 (95% confidence interval 1.00 to 1.87)]. Over follow-up, the economic evaluation discounted results showed that best endovascular treatment-first was associated with £1690 less hospital costs compared to vein bypass-first. The cost utility analysis showed that compared to vein bypass-first, best endovascular treatment-first was associated with £224 and £2233 less discounted hospital costs and 0.016 and 0.085 discounted quality-adjusted life-year gain after 2 and 3 years from randomisation. A best endovascular treatment-first revascularisation strategy was associated with better amputation-free survival, which was largely driven by fewer deaths. Overall, the economic evaluation results suggest that best endovascular treatment-first dominates vein bypass-first in the cost-effectiveness analysis and cost–utility analysis as it was less costly and more effective than a vein bypass-first strategy. Between 22 July 2014 and 30 November 2020, 345 participants were randomised, 172 to the VB-first group and 173 to the BET-first group. The baseline characteristics of the two groups were similar. Major amputation or death occurred in 108 (63%) of 172 patients in the VB-first group and 92 (53%) of 173 patients in the BET-first group {adjusted HR 1.35 [95% confidence interval (CI) 1.02 to 1.80]; p = 0.037}. Ninety-one (53%) of 172 patients in the VB-first group and 77 (45%) of 173 patients in the BET-first group died [adjusted HR 1.37 (95% CI 1.00 to 1.87)]. In both groups the commonest causes of morbidity and mortality, including those occurring within 30 days of their first revascularisation, were cardiovascular and respiratory events. Over follow-up, the economic evaluation results showed that BET-first was associated with £1690 less hospital costs compared to VB-first with additional survival without amputation. The cost utility analysis showed that compared to VB-first, BET-first was associated with £2524 and £2233 less hospital costs and 0.016 and 0.085 QALY gain after 2 and 3 years from randomisation. In the BASIL-2 trial, a BET-first revascularisation strategy was associated with a better AFS, which was largely driven by fewer deaths in the BET-first group. In both the CUA and cost-effectiveness analysis (CEA) analyses and from a NHS and societal perspective BET-first dominated VB-first and is therefore a highly cost-effective intervention for the NHS. These data suggest a greater role for BET in the management of patients with CLTI who require an IP revascularisation to restore limb perfusion. In patients with CLTI who required an IP, with or without an additional more proximal infra-inguinal revascularisation procedure, to restore limb perfusion, a BET-first revascularisation strategy was associated with reduced hospital costs (£1690) and improved AFS (0.429 years), out to 7 years following randomisation. BET-first therefore dominated VB-first in the CEA. Similarly, in the health-related quality of life the CUA, BET-first was cost-saving with improved QALYs (£2524 and £2233 less hospital costs and 0.016 and 0.085 more QALYs at 2 and 3 years, respectively) and so dominated VB-first. This economic analysis therefore shows that BET-first is a cost-effective option from an NHS and societal perspective. The sensitivity analysis supported the base-case analysis and BET-first was found to be cost-effective at different willingness-to-pay thresholds. Similar findings were found in all other scenario analyses when considering costs of primary and other hospital healthcare services, taking a broader societal perspective, which includes out-of-pocket expenditure and the costs associated with productivity loss, patient’s adherence to study protocol, the impact of imputation by focusing on participants with complete hospital cost and EQ-5D-5L data only. However, these findings should be interpreted cautiously given the large number of imputed cost values and the substantial probability of a very small QALY difference.

Authors' methods: Superiority, open, pragmatic, multicentre, phase III randomised trial. Thirty-nine vascular surgery units in the United Kingdom, and one each in Sweden and Denmark. Patients with chronic limb-threatening ischaemia due to atherosclerotic peripheral arterial disease who required an infra-popliteal revascularisation, with or without an additional more proximal infra-inguinal revascularisation procedure, to restore limb perfusion. A vein bypass-first or a best endovascular treatment-first infra-popliteal, with or without an additional more proximal infra-inguinal revascularisation strategy. The primary outcome was amputation-free survival. Secondary outcomes included overall survival, major amputation, further revascularisation interventions, major adverse limb event, health-related quality of life and serious adverse events. Participants were randomised to a vein bypass-first or a best endovascular treatment-first revascularisation strategy. The original sample size of 600 participants (247 events) was based on a hazard ratio of 0.66 with amputation-free survival rates of 0.72, 0.62, 0.53, 0.47 and 0.35 in years 1–5 in the best endovascular treatment-first group with 90% power and alpha at p = 0.05. The sample size was revised to an event-based approach as a result of increased follow-up time due to slower than anticipated recruitment rates. Participants were followed up for a minimum of 2 years. A cost-effectiveness analysis was employed to estimate differences in total hospital costs and amputation-free survival between the groups. Additionally, a cost–utility analysis was carried out and the total cost and quality-adjusted life-years, 2 and 3 years after randomisation were used. Recruiting patients to the Bypass versus Angioplasty in Severe Ischaemia of the Leg Trial-2 trial was difficult and the target number of events was not achieved. Superiority, open-label, pragmatic, multicentre, phase III randomised trial. Thirty-nine vascular surgery units in the United Kingdom, and one each in Sweden and Denmark. Those with CLTI due to atherosclerotic PAD and who required an IP revascularisation, with or without an additional more proximal infra-inguinal revascularisation procedure, to restore limb perfusion. A VB-first or a BET-first IP, with or without an additional more proximal infra-inguinal revascularisation strategy, to restore limb perfusion. Most VBs were constructed with great saphenous vein and originated from the common or superficial femoral arteries. Most endovascular interventions comprised plain balloon angioplasty with selective use of plain or drug-eluting stents.

Project Status: Completed

URL for project: https://www.journalslibrary.nihr.ac.uk/programmes/hta/12/35/45

Year Published: 2024

URL for published report: https://www.journalslibrary.nihr.ac.uk/hta/YTFV4524

URL for additional information: English

English language abstract: An English language summary is available

Publication Type: Full HTA

Country: England, United Kingdom

DOI: 10.3310/YTFV4524

Organisation Name: NIHR Health Technology Assessment programme

Contact Address: NIHR Journals Library, National Institute for Health and Care Research, Evaluation, Trials and Studies Coordinating Centre, Alpha House, University of Southampton Science Park, Southampton SO16 7NS, UK

Contact Name: journals.library@nihr.ac.uk

Contact Email: journals.library@nihr.ac.uk