Editor's Choice - Bypass versus Angioplasty for Severe Ischaemia of the Leg (BASIL) Prospective Cohort Study and the Generalisability of the BASIL-2 Randomised Controlled Trial

OBJECTIVE: The Bypass versus Angioplasty in Severe Ischaemia of the Leg-2 (BASIL-2) randomised controlled trial has shown that, for patients with chronic limb threatening ischaemia (CLTI) who require an infrapopliteal (IP) revascularisation a vein bypass (VB) first revascularisation strategy led to a 35% increased risk of major amputation or death when compared with a best endovascular treatment (BET) first revascularisation strategy. The study aims are to place the BASIL-2 trial within the context of the CLTI patient population as a whole and to investigate the generalisability of the BASIL-2 outcome data.METHODS: This was an observational, single centre prospective cohort study. Between 24 June 2014 and 31 July 2018, the BASIL Prospective Cohort Study (PCS) was performed which used BASIL-2 trial case record forms to document the characteristics, initial and subsequent management, and outcomes of 471 consecutive CLTI patients admitted to an academic vascular centre. Ethical approval was obtained, and all patients provided fully informed written consent. Follow up data were censored on 14 December 2022.RESULTS: Of the 238 patients who required an infrainguinal revascularisation, 75 (32%) had either IP bypass (39 patients) or IP BET (36 patients) outside BASIL-2. Seventeen patients were initially randomised to BASIL-2. A further three patients who did not have an IP revascularisation as their initial management were later randomised in BASIL-2. Therefore, 95/471 (20%) of patients had IP revascularisation (16% outside, 4% inside BASIL-2). Differences in amputation free survival, overall survival, and limb salvage between IP bypass and IP BET performed outside BASIL-2 were not subject to hypothesis testing due to the small sample size. Reasons for non-randomisation into the trial were numerous, but often due to anatomical and technical considerations.CONCLUSION: CLTI patients who required an IP revascularisation procedure and were subsequently randomised into BASIL-2 accounted for a small subset of the CLTI population as a whole. For a wide range of patient, limb, anatomical and operational reasons, most patients in this cohort were deemed unsuitable for randomisation in BASIL-2. The results of BASIL-2 should be interpreted in this context.</p

The cost-effectiveness of domiciliary non-invasive ventilation in patients with end-stage chronic obstructive pulmonary disease:a systematic review and economic evaluation

Background: Chronic obstructive pulmonary disease (COPD) is a chronic progressive lung disease characterised by non-reversible airflow obstruction. Exacerbations are a key cause of morbidity and mortality and place a considerable burden on health-care systems. While there is evidence that patients benefit from non-invasive ventilation (NIV) in hospital during an acute exacerbation, evidence supporting home use for more stable COPD patients is limited. In the UK, domiciliary NIV is considered on health economic grounds in patients after three hospital admissions for acute hypercapnic respiratory failure. Objective: To assess the clinical effectiveness and cost-effectiveness of domiciliary NIV by systematic review and economic evaluation. Data sources: Bibliographic databases, conference proceedings and ongoing trial registries up to September 2014. Methods: Standard systematic review methods were used for identifying relevant clinical effectiveness and cost-effectiveness studies assessing NIV compared with usual care or comparing different types of NIV. Risk of bias was assessed using Cochrane guidelines and relevant economic checklists. Results for primary effectiveness outcomes (mortality, hospitalisations, exacerbations and quality of life) were presented, where possible, in forest plots. A speculative Markov decision model was developed to compare the cost-effectiveness of domiciliary NIV with usual care from a UK perspective for post-hospital and more stable populations separately. Results: Thirty-one controlled effectiveness studies were identified, which report a variety of outcomes. For stable patients, a modest volume of evidence found no benefit from domiciliary NIV for survival and some non-significant beneficial trends for hospitalisations and quality of life. For post-hospital patients, no benefit from NIV could be shown in terms of survival (from randomised controlled trials) and findings for hospital admissions were inconsistent and based on limited evidence. No conclusions could be drawn regarding potential benefit from different types of NIV. No cost-effectiveness studies of domiciliary NIV were identified. Economic modelling suggested that NIV may be cost-effective in a stable population at a threshold of £30,000 per quality-adjusted life-year (QALY) gained (incremental cost-effectiveness ratio £28,162), but this is associated with uncertainty. In the case of the post-hospital population, results for three separate base cases ranged from usual care dominating to NIV being cost-effective, with an incremental cost-effectiveness ratio of less than £10,000 per QALY gained. All estimates were sensitive to effectiveness estimates, length of benefit from NIV (currently unknown) and some costs. Modelling suggested that reductions in the rate of hospital admissions per patient per year of 24% and 15% in the stable and post-hospital populations, respectively, are required for NIV to be cost-effective. Limitations: Evidence on key clinical outcomes remains limited, particularly quality-of-life and long-term (> 2 years) effects. Economic modelling should be viewed as speculative because of uncertainty around effect estimates, baseline risks, length of benefit of NIV and limited quality-of-life/utility data. Conclusions: The cost-effectiveness of domiciliary NIV remains uncertain and the findings in this report are sensitive to emergent data. Further evidence is required to identify patients most likely to benefit from domiciliary NIV and to establish optimum time points for starting NIV and equipment settings. Future work recommendations: The results from this report will need to be re-examined in the light of any new trial results, particularly in terms of reducing the uncertainty in the economic model. Any new randomised controlled trials should consider including a sham non-invasive ventilation arm and/or a higher- and lower-pressure arm. Individual participant data analyses may help to determine whether or not there are any patient characteristics or equipment settings that are predictive of a benefit of NIV and to establish optimum time points for starting (and potentially discounting) NIV. Study registration: This study is registered as PROSPERO CRD42012003286. Funding: The National Institute for Health Research Health Technology Assessment programme

A Comparison of Clinical Outcomes Between Primary Bypass and Secondary Bypass After Failed Plain Balloon Angioplasty in the Bypass versus Angioplasty for Severe Ischaemia of the Limb (BASIL) Trial.

OBJECTIVE Chronic limb threatening ischaemia (CLTI) is a growing global health problem. The UK NIHR HTA funded BASIL trial is still the only randomised controlled trial to have compared a "bypass surgery first" with a "plain balloon angioplasty (PBA) first" strategy for the management of CLTI. In patients who were likely to survive for 2 years and had a suitable vein, primary bypass (PB) was associated with better clinical outcomes. Furthermore, PBA was associated with a high technical and clinical failure rate and many went on to have secondary bypass (SB). This study aimed at comparing clinical outcomes following PB and SB in the BASIL trial. METHODS Demographic, procedural, and outcome data were obtained from the BASIL case report forms. Outcomes were amputation free survival (AFS), limb salvage (LS), overall survival (OS), and freedom from revascularisation (FFR). The SB cohort comprises patients whose first trial intervention was PBA and who subsequently underwent bypass during follow up. The PB cohort comprises those patients whose first trial intervention was bypass. RESULTS The 190 PB and 49 SB patients were well matched except that the SB patients were more likely to be current smokers. At a median of 7 years, PB was associated with better AFS (PB 60% vs. SB 40%; HR 1.58, p = .04), LS (PB 85% vs. SB 73%, p = .06), and OS (PB 68% vs. 51%, p = .06). FFR was equivalent (PB 53% vs. 53%, p = .3). CONCLUSION In the BASIL trial, clinical outcomes following PB were significantly better than in patients undergoing SB after failed PBA. Prior to treating patients with CLTI with primary PBA, clinicians should consider that if this should fail, the outcome of attempted subsequent bypass is likely to be significantly worse than if PB were attempted