Bypass Versus Angioplasty In Severe Ischaemia Of The Leg Research Articles

Bypass versus Angioplasty in Severe Ischaemia of the Leg (BASIL)-2 Trial: Analysis of the Timing and Causes of Death in Participants Randomised to an Infrapopliteal Vein Bypass or Best Endovascular Treatment First Revascularisation Strategy

The Bypass versus Angioplasty in Severe Ischaemia of the Leg (BASIL)-2 trial enrolled participants with chronic limb threatening ischaemia who required an infrapopliteal, with or without a femoropopliteal, revascularisation procedure to restore limb perfusion. Participants randomised to a vein bypass (VB) first revascularisation strategy were over one third more likely than those randomised to a best endovascular treatment (BET) first revascularisation strategy to die from any cause during a median follow up of 40.0 (interquartile range 20.9, 60.6) months. The aim was to describe the timing and causes of death in BASIL-2 as a first step towards trying to better understand why randomisation to a VB first revascularisation strategy was associated with this excess mortality. A 10 person international panel comprising vascular and endovascular surgeons as well as vascular interventional radiologists, who had all been principal investigators in BASIL-2, took part in a modified Delphi consensus exercise to adjudicate the primary cause of death and, in particular, whether the cause was primarily cardiac or non-cardiac. In 151/168 deaths (89.9%) the Delphi panel achieved a consensus regarding the cause of death being probably cardiac or non-cardiac. In the BET group, 16/77 deaths (21%) were classified as probably cardiac compared with 32/91 (35%) in the VB group (unadjusted subdistribution hazard ratio 2.16, 95% confidence interval [CI] 1.20 - 3.87; unadjusted cause specific hazard ratio 2.15, 95% CI 1.19 - 3.90). At the point of randomisation, 64/344 (18.6%), 37/344 (10.8%), and 40/342 (9%) participants had a previous myocardial infarction (MI), percutaneous coronary intervention (PCI), and coronary artery bypass graft (CABG), respectively. There was no evidence of varying treatment effects for cause of death in subgroup analyses of previous PCI, CABG, or MI. The excess mortality observed in the VB first revascularisation strategy group in BASIL-2 was largely due to deaths that were adjudicated by the Delphi panel as probably primarily cardiac. These excess cardiac deaths were observed throughout follow up and there was no evidence of non-proportional hazards. Further work is ongoing to try to better understand the reasons for these findings.

Relationship Between Global Anatomic Staging System (GLASS) and Clinical Outcomes Following Revascularisation for Chronic Limb Threatening Ischaemia in the Bypass Versus Angioplasty in Severe Ischaemia of the Leg (BASIL)-1 Trial

The Global Vascular Guideline on chronic limb threatening ischaemia (CLTI) has introduced the Global Limb Anatomic Staging System (GLASS) as a new angiographic scoring system. However, the relationship between GLASS and outcomes following revascularisation has not previously been studied. Using pre-intervention angiograms the relationship between GLASS and immediate technical failure (ITF), amputation free survival (AFS), limb salvage (LS), overall survival (OS), and freedom from major adverse limb events (FF-MALE) was examined in 377 patients undergoing endovascular therapy (EVT, n = 213) or bypass surgery (BS, n = 164) in the Bypass versus Angioplasty in Severe Ischaemia of the Leg (BASIL)-1 trial (randomised 1999–2004). There was no significant difference in GLASS between cohorts. There was a significant relationship between ITF and GLASS in EVT (I 14%, II 15%, III 28%, p = .049). GLASS was significantly related to AFS (hazard ratio [HR], 1.37; 95% CI 1.01–1.85; p = .042), LS (HR 1.96; 95 % CI 1.12–3.43; p = .018), and FF-MALE (HR 1.49; 95% CI 1.04–1.87; p = .028) in the EVT cohort. In BS patients, there was no relationship between GLASS and these outcomes. FF-MALE was significantly worse after EVT than BS in GLASS II (p = .038) and III (p = .001). Among the subgroup of patients with femoropopliteal (FP) disease (BS, n = 109 or EVT, n = 159), FF-MALE was significantly higher after BS than EVT (p < .001). The superiority of BS over EVT with increasing GLASS FP grade was greater in the analysis of patients using vein grafts. In the BASIL-1 cohort, GLASS is associated with outcomes following EVT but not BS. Although further validation in contemporary CLTI cohorts is required, GLASS seems likely be useful in shared decision making and for stratifying patients in future trials.

Comparison of Clinical Outcomes in Patients Selected for Infra-Popliteal Bypass or Plain Balloon Angioplasty for Chronic Limb Threatening Ischemia Between 2009 and 2013.

Introduction:A published subgroup analysis of the Bypass versus Angioplasty in Severe Ischaemia of the Leg (BASIL)-1 trial suggests that, in patients with chronic limb threatening ischemia (CLTI) due to infra-popliteal (IP) disease, clinical outcomes are better following vein bypass surgery (BS) than after plain balloon angioplasty (PBA). The aim of the present study is to determine if clinical outcomes following IP revascularization in our unit are concordant with those found in BASIL-1.Methods:We analyzed prospectively gathered data pertaining to 137 consecutive CLTI patients undergoing IP PBA or BS between 2009 and 2013. We compared 30-day morbidity and mortality, days in hospital (index admission and out to 12-months), amputation free survival (AFS), overall survival (OS), limb salvage (LS), and freedom from arterial re-intervention (FFR). Patient outcomes were censored on 1 February 2017, providing a minimum 3 years follow-up.Results:Patients undergoing BS (73/137, 47%) tended to be younger, have less comorbidity, and were more likely to be on best medical therapy (BMT). BS patients spent more days in hospital during the index admission (median 9 vs 5, p = .003), but not out to 12 months (median 15 vs 13, NS). BS patients suffered more 30-day morbidity (36% vs 10%, p < .001), mainly due to infective complications, but not mortality (3.1% vs 6.8%, NS). AFS (p = .001) and OS (p < .001), but not LS or FFR, were better after BS.Conclusions:CLTI patients selected for revascularization by means of IP BS had better long-term outcomes in terms of AFS and OS, but not FFR or LS. Although we await the results of the BASIL-2 trial, current data support the BASIL-1 sub-group analysis which suggests that patients requiring revascularization for IP disease should have BS where possible and that PBA should usually be reserved for patients who are not suitable for BS.

Editor's Choice – Relationship Between Global Limb Anatomic Staging System (GLASS) and Clinical Outcomes Following Revascularisation for Chronic Limb Threatening Ischaemia in the Bypass Versus Angioplasty in Severe Ischaemia of the Leg (BASIL)-1 Trial

The Global Vascular Guideline on chronic limb threatening ischaemia (CLTI) has introduced the Global Limb Anatomic Staging System (GLASS) as a new angiographic scoring system. However, the relationship between GLASS and outcomes following revascularisation has not previously been studied. Using pre-intervention angiograms the relationship between GLASS and immediate technical failure (ITF), amputation free survival (AFS), limb salvage (LS), overall survival (OS), and freedom from major adverse limb events (FF-MALE) was examined in 377 patients undergoing endovascular therapy (EVT, n=213) or bypass surgery (BS, n=164) in the Bypass versus Angioplasty in Severe Ischaemia of the Leg (BASIL)-1 trial (randomised 1999-2004). There was no significant difference in GLASS between cohorts. There was a significant relationship between ITF and GLASS in EVT (I 14%, II 15%, III 28%, p=.049). GLASS was significantly related to AFS (hazard ratio [HR], 1.37; 95% CI 1.01-1.85; p=.042), LS (HR 1.96; 95 % CI 1.12-3.43; p=.018), and FF-MALE (HR 1.49; 95% CI 1.04-1.87; p=.028) in the EVT cohort. In BS patients, there was no relationship between GLASS and these outcomes. FF-MALE was significantly worse after EVT than BS in GLASS II (p=.038) and III (p=.001). Among the subgroup of patients with femoropopliteal (FP) disease (BS, n=109 or EVT, n=159), FF-MALE was significantly higher after BS than EVT (p<.001). The superiority of BS over EVT with increasing GLASS FP grade was greater in the analysis of patients using vein grafts. In the BASIL-1 cohort, GLASS is associated with outcomes following EVT but not BS. Although further validation in contemporary CLTI cohorts is required, GLASS seems likely be useful in shared decision making and for stratifying patients in future trials.

Female Gender was Associated with Improved Clinical Outcomes at 1 and 3 Years in the Bypass Versus Angioplasty in Severe Ischaemia of the Limb Trial

Introduction: Retrospective cohort studies have suggested that women are more likely to suffer from worse outcomes following peripheral arterial interventions. However, this has never been examined within the confines of a randomised controlled trial. The aim of the present study, therefore, was to examine the relationship between gender in the Bypass versus Angioplasty in Severe Ischaemia of the Leg (BASIL) trial which compared a bypass surgery (BSX) first with a balloon-angioplasty (BAP) first revascularisation strategy for severe limb ischaemia (SLI) due to infrainguinal disease. Methods - Data were obtained from BASIL trial case record forms. Cox proportional hazard models were used to examine the relationship between amputation free survival (AFS), freedom from major adverse limb events (FF-MALE) and overall survival (OS) at 1 and 3 years and primary intervention, gender, age, clinical presentation and ankle to brachial pressure index (ABPI). Results - 452 patients were randomised between 1999-2004 (228 to a BSX-first and 224 to a BAP-first strategy) of whom 128/269 men and 67/183 women had BSX as their primary intervention. Women were older (74.2 vs 71.8 years, p ≤0.05 95% CI -4.0 - -0.7), less likely to be smokers or have diabetes, and more likely to have untreated hypercholesterolaemia. Baseline creatinine was significantly higher in men (119 μmol/L vs 102 μmol/L, p<0.05, CI 5.1-28.9). ABPI and severity of clinical presentation was similar between men and women as were length of hospital stay and 30-day complications. At 1 year women had better AFS (HR 0.58 (CI 0.35, 0.95), p=0.03), but there were no differences in survival or re-intervention. At 3 years women had better AFS (HR 0.55 (CI 0.37, 0.84), p=0.01) and OS (HR 0.54 (0.34, 0.87), p=0.01) and there was a trend towards better FF-MALE. Conclusion - These results suggest that men and women presenting with SLI have different risk factors. The data also suggest that in a cohort of people with SLI treated within an RCT, long-term outcomes are better for women than for men. Further analysis of data from on-going trials such as BASIL 2 and 3, and BEST-CLI will be required in order to fully define the relationship between gender and outcome in patients presenting with chronic limb threatening ischaemia (CLTI).

The Relationship Between Severity of Arterial Disease Quantified by the Bollinger Angiographic Scoring Method, Presenting Symptoms and Signs and Preoperative Comorbidities in the Bypass Versus Angioplasty in Severe Ischaemia of the Leg (BASIL) Trial

The Relationship Between Severity of Arterial Disease Quantified by the Bollinger Angiographic Scoring Method, Presenting Symptoms and Signs and Preoperative Comorbidities in the Bypass Versus Angioplasty in Severe Ischaemia of the Leg (BASIL) Trial

Validation of randomized controlled trial-derived models for the prediction of postintervention outcomes in chronic limb-threatening ischemia

BackgroundChronic limb-threatening ischemia (CLTI) represents the most severe form of peripheral artery disease and has a large impact on quality of life, morbidity, and mortality. Interventions are aimed at improving tissue perfusion and averting amputation and secondary cardiovascular complications with an optimal risk-benefit ratio. Several prediction models regarding postprocedural outcomes in CLTI patients have been developed on the basis of randomized controlled trials to improve clinical decision-making. We aimed to determine model performance in predicting clinical outcomes in selected CLTI cohorts. MethodsThis study validated the Bypass versus Angioplasty in Severe Ischaemia of the Leg (BASIL), Finland National Vascular registry (FINNVASC), and Prevention of Infrainguinal Vein Graft Failure (PREVENT III) models in data sets from a peripheral artery disease registry study (Athero-Express) and two randomized controlled trials of CLTI in The Netherlands, Rejuvenating Endothelial Progenitor Cells via Transcutaneous Intra-arterial Supplementation (JUVENTAS) and Percutaneous Transluminal Angioplasty and Drug-eluting Stents for Infrapopliteal Lesions in Critical Limb Ischemia (PADI). Receiver operating characteristic (ROC) curve analysis was used to calculate their predictive capacity. The primary outcome was amputation-free survival (AFS); secondary outcomes were all-cause mortality and amputation at 12 months after intervention. ResultsThe BASIL and PREVENT III models showed predictive values regarding postintervention mortality in the JUVENTAS cohort with an area under the ROC curve (AUC) of 81% and 70%, respectively. Prediction of AFS was poor to fair (AUC, 0.60-0.71) for all models in each population, with the highest predictive value of 71% for the BASIL model in the JUVENTAS population. The FINNVASC model showed the highest predictive value regarding amputation risk in the PADI population with AUC of 78% at 12 months. ConclusionsIn general, all models performed poor to fair in predicting mortality and amputation. Because the BASIL model performed best in predicting AFS, we propose use of the BASIL model to aid in the clinical decision-making process in CLTI. However, improvements in performance have to be made for any of these models to be of real additional value in clinical practice.

Survival prediction in patients with chronic limb-threatening ischemia who undergo infrainguinal revascularization

Accurate survival prediction critically influences decision-making in caring for patients with chronic limb-threatening ischemia (CLTI). The Bypass versus Angioplasty in Severe Ischaemia of the Leg (BASIL) trial demonstrated that in patients who survived >2years, there was a significant advantage to infrainguinal bypass compared with endovascular intervention, which increased with time. Validated survival models for patients with CLTI are lacking. The Vascular Quality Initiative was interrogated for patients who underwent infrainguinal bypass or endovascular intervention for CLTI (January 2003-February 2017). Cox survival models were generated using only preoperative variables. Survival at 30days, 2years, and 5years was modeled separately. Patients were defined as low risk (30-day survival >97% and 2-year survival >70%), medium risk (30-day survival 95%-97% or 2-year survival 50%-70%), and high-risk (30-day survival<95% or 2-year survival<50%). Among 38,470 unique CLTI patients, 63% (n= 24,214) underwent endovascular intervention and 37% (n= 14,256) underwent infrainguinal bypass. Kaplan-Meier estimates of overall survival at 30days, 2years, and 5years were 98%, 81%, and 69%, respectively. The proportion of patients in the low-, medium-, and high-risk groups was 84%, 10%, and 6.5%, respectively. Patients in the low-risk group were significantly less likely to undergo endovascular intervention compared with those in the high-risk group (low risk, 59% endovascular; high risk, 75% endovascular; P< .0001). Independent predictors of death were similar in all three models, with greatest magnitude of effect associated with age >80years, oxygen-dependent chronic obstructive pulmonary disease, stage 5 chronic kidney disease, and bedbound status. The C index for the 30-day model, 2-year model, and 5-year model was 0.76, 0.72, and 0.71, respectively. Procedure type (open or endovascular) was not significant in any models and did not have an impact on C indices. These survival prediction models, derived from a large U.S. cohort of patients who underwent revascularization for CLTI, demonstrated good performance and should be validated. Most CLTI patients considered candidates for limb salvage were of average perioperative risk and were predicted to survive beyond 2years. These models can differentiate patients into low-, medium-, and high-risk groups to facilitate evidence-based revascularization recommendations that are consistent with current treatment guidelines.

Survival prediction in patients with chronic limb-threatening ischemia who undergo infrainguinal revascularization

ObjectiveAccurate survival prediction critically influences decision-making in caring for patients with chronic limb-threatening ischemia (CLTI). The Bypass versus Angioplasty in Severe Ischaemia of the Leg (BASIL) trial demonstrated that in patients who survived >2 years, there was a significant advantage to infrainguinal bypass compared with endovascular intervention, which increased with time. Validated survival models for patients with CLTI are lacking. MethodsThe Vascular Quality Initiative was interrogated for patients who underwent infrainguinal bypass or endovascular intervention for CLTI (January 2003-February 2017). Cox survival models were generated using only preoperative variables. Survival at 30 days, 2 years, and 5 years was modeled separately. Patients were defined as low risk (30-day survival >97% and 2-year survival >70%), medium risk (30-day survival 95%-97% or 2-year survival 50%-70%), and high-risk (30-day survival <95% or 2-year survival <50%). ResultsAmong 38,470 unique CLTI patients, 63% (n = 24,214) underwent endovascular intervention and 37% (n = 14,256) underwent infrainguinal bypass. Kaplan-Meier estimates of overall survival at 30 days, 2 years, and 5 years were 98%, 81%, and 69%, respectively. The proportion of patients in the low-, medium-, and high-risk groups was 84%, 10%, and 6.5%, respectively. Patients in the low-risk group were significantly less likely to undergo endovascular intervention compared with those in the high-risk group (low risk, 59% endovascular; high risk, 75% endovascular; P < .0001). Independent predictors of death were similar in all three models, with greatest magnitude of effect associated with age >80 years, oxygen-dependent chronic obstructive pulmonary disease, stage 5 chronic kidney disease, and bedbound status. The C index for the 30-day model, 2-year model, and 5-year model was 0.76, 0.72, and 0.71, respectively. Procedure type (open or endovascular) was not significant in any models and did not have an impact on C indices. ConclusionsThese survival prediction models, derived from a large U.S. cohort of patients who underwent revascularization for CLTI, demonstrated good performance and should be validated. Most CLTI patients considered candidates for limb salvage were of average perioperative risk and were predicted to survive beyond 2 years. These models can differentiate patients into low-, medium-, and high-risk groups to facilitate evidence-based revascularization recommendations that are consistent with current treatment guidelines.

“Endovascular first” Strategies are not for Every Patient

The term “endovascular first” was made popular by research but has gradually become accepted as a standard approach to lower limb revascularisation: “give it a go” endovascularly then bypass if this fails. This was always a misappropriation of the research data, and the meta-analysis by Hossain et al.1Hossain S. Leblanc D. Farber A. Power A. DeRose G. Duncan A. et al.Infrainguinal bypass following failed endovascular intervention compared with primary bypass: a systematic review and meta-analysis.Eur J Vasc Endovasc Surg. 2019; 57: 382-391Abstract Full Text Full Text PDF Scopus (9) Google Scholar shows exactly why we need to be cautious with widespread adoption of a practice without clear evidence. Endovascular first strategies were already popular when the initial results of the BASIL1 trial were reported as balloon angioplasty first is broadly similar to vein bypass first.2Adam D.J. Beard J.D. Cleveland T. Bell J. Bradbury A.W. Forbes J.F. et al.BASIL trial participants. Bypass versus angioplasty in severe ischaemia of the leg (BASIL): multicentre, randomised controlled trial.Lancet. 2005; 366: 1925-1934Abstract Full Text Full Text PDF PubMed Scopus (1610) Google Scholar Longer term, non-powered comparisons from BASIL soon showed a more subtle picture than this,3Bradbury A.W. Adam D.J. Bell J. Forbes J.F. Fowkes F.G. Gillespie I. 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): 1-210Crossref Scopus (125) Google Scholar as did a wealth of other data,4Antoniou G.A. Georgiadis G.S. Antoniou S.A. Makar R.R. Smout J.D. Torella F. Bypass surgery for chronic lower limb ischaemia.Cochrane Database Syst Rev. 2017; 4: CD002000PubMed Google Scholar but the message in clinical practice had already become endovascular first in many units. By this time the enthusiasm for endovascular intervention was high, and arguing against an endovascular first approach was met with counter arguments over improved technology, better patient selection, and better medication protocols. However, if the results of this meta-analysis are to be believed, patients undergoing bypass after failed endovascular intervention fare worse than if they are offered bypass first. This is an important message because the long-term results of the BASIL trial showed that vein bypass was superior to endovascular intervention in the long term, with the caveat that it was never designed with statistical power for observations over this amount of time.3Bradbury A.W. Adam D.J. Bell J. Forbes J.F. Fowkes F.G. Gillespie I. 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): 1-210Crossref Scopus (125) Google Scholar Cohort results have been more conflicted.1Hossain S. Leblanc D. Farber A. Power A. DeRose G. Duncan A. et al.Infrainguinal bypass following failed endovascular intervention compared with primary bypass: a systematic review and meta-analysis.Eur J Vasc Endovasc Surg. 2019; 57: 382-391Abstract Full Text Full Text PDF Scopus (9) Google Scholar These caveats affect the ability of this meta-analysis to make definitive recommendations. It predominantly includes cohort studies that will all suffer from selection bias concerning the severity of atherosclerosis, patient selection, and operator outcomes. The cohorts were generally small with low event rates, so the meta-analyses are skewed by results from the larger studies favouring primary bypass.1Hossain S. Leblanc D. Farber A. Power A. DeRose G. Duncan A. et al.Infrainguinal bypass following failed endovascular intervention compared with primary bypass: a systematic review and meta-analysis.Eur J Vasc Endovasc Surg. 2019; 57: 382-391Abstract Full Text Full Text PDF Scopus (9) Google Scholar In addition to this, the aforementioned counter arguments for endovascular intervention are also true in that everything has changed since many of these studies were published. Whether the mechanism by which endovascular intervention potentially affects any subsequent bypass has also changed is unknown, because that mechanism was unclear in the first place. The summary is that this analysis should strike a note of caution into our endovascular decision making. The patient with a useable vein and a more complex endovascular option needs careful consideration and counselling for the best outcomes. Editor's Choice – Infrainguinal Bypass Following Failed Endovascular Intervention Compared With Primary Bypass: A Systematic Review and Meta-AnalysisEuropean Journal of Vascular and Endovascular SurgeryVol. 57Issue 3PreviewPatients with infrainguinal peripheral arterial disease often undergo multiple revascularisation procedures. Although many centres have adopted an endovascular first approach, some are reluctant to do so for fear of compromising the outcomes of any subsequent bypasses. All studies that compared the outcomes of primary infrainguinal bypass with bypass after failed endovascular intervention were analysed. Full-Text PDF Open Archive

Invited commentary

The authors are to be congratulated for the detailed examination of the Vascular Quality Initiative (VQI) database to obtain a glimpse of the real-world outcomes of patients with critical limb ischemia (CLI) treated with endovascular peripheral vascular intervention (PVI) vs lower extremity bypass (LEB). Not surprisingly, PVI patients were found to have significantly more comorbidities, lower adjusted perioperative mortalities, and shorter lengths of stay. The perioperative mortality advantage disappeared in the cohorts that focused on patients with better operative risk and simpler anatomy. LEB patients, similar to previous studies, had improved 3-year survivals and improved survival free of major adverse limb events in the overall cohort. This study raises important questions, but similar to previous evaluations of endovascular therapy CLI and Vascular Quality Initiative reports, has significant limitations. Follow-up at 1 year was <50%, and no hemodynamic or detailed anatomic information was available. The most reliable 3-year data (based on Social Security data) confirm the survival advantage to patients undergoing LEB. So how are we to use these data in our own selection of PVI vs LEB for CLI patients? Perhaps this study supports most vascular surgeons' bias that PVI (or even serial PVIs) is the best way to bring our most severely ill CLI patients to the finish line with their legs intact; hopefully, in relative comfort with wounds healed or healing. Unfortunately, this study does little to inform our treatment of the great majority of our patients who live ≥2 years beyond the first intervention for CLI. Vascular surgeons are the most well-equipped clinicians to manage patients with CLI because only we can offer these patients the full range of treatment options, including PVI and LEB. The best application of these complementary techniques depends on accurate comparative effectiveness data based on precise anatomic criteria, hemodynamic results, patency rates, limb salvage rates, wound healing rates, quality of life, and cost effectiveness. As the authors rightly point out, such data awaits completion of randomized prospective trials such as the ongoing Best Endovascular Versus Best Surgical Therapy in Patients With CLI (BEST) trial. I would ask you to consider for one moment the effect previous randomized prospective vascular surgery trials, such as Asymptomatic Carotid Artery Stenosis Study (ACAS), North American Symptomatic Carotid Endarterectomy Trial (NASCET), Carotid Revascularization Endarterectomy vs Stent Trial (CREST), Comparison of Endovascular Aneurysm Repair with Open Repair in Patients with Abdominal Aortic Aneurysm (EVAR), Dutch Randomised Endovascular Aneurysm Management (DREAM), Aneurysm Detection and Management (ADAM), Bypass Versus Angioplasty in Severe Ischaemia of the Leg (BASIL) and Edifoligide for the Prevention of Infrainguinal Vein Graft Fail (PREVENT) among others, have had on our education of patients and trainees as well as our daily practice of vascular and endovascular surgery. We must actively support and enroll in the BEST trial to bring it to successful completion to generate similar data to help guide us in the treatment of our most challenging CLI patients. Only then will vascular surgeons know how to best use our complementary tools of PVI and LEB. Comparison of open and endovascular treatment of patients with critical limb ischemia in the Vascular Quality InitiativeJournal of Vascular SurgeryVol. 63Issue 4PreviewThere is significant controversy in the management of critical limb ischemia (CLI) arising from infrainguinal peripheral arterial disease. We sought to compare practice patterns and perioperative and long-term outcomes for patients undergoing lower extremity bypass (LEB) and percutaneous vascular interventions (PVIs) for CLI in the Vascular Quality Initiative (VQI). Full-Text PDF Open Archive

A comparative evaluation of risk-adjustment models for benchmarking amputation-free survival after lower extremity bypass

Providing patients and payers with publicly reported risk-adjusted quality metrics for the purpose of benchmarking physicians and institutions has become a national priority. Several prediction models have been developed to estimate outcomes after lower extremity revascularization for critical limb ischemia, but the optimal model to use in contemporary practice has not been defined. We sought to identify the highest-performing risk-adjustment model for amputation-free survival (AFS) at 1year after lower extremity bypass (LEB). We used the national Society for Vascular Surgery Vascular Quality Initiative (VQI) database (2003-2012) to assess the performance of three previously validated risk-adjustment models for AFS. The Bypass versus Angioplasty in Severe Ischaemia of the Leg (BASIL), Finland National Vascular (FINNVASC) registry, and the modified Project of Ex-vivo vein graft Engineering via Transfection III (PREVENT III [mPIII]) risk scores were applied to the VQI cohort. A novel model for 1-year AFS was also derived using the VQI data set and externally validated using the PIII data set. The relative discrimination (Harrell c-index) and calibration (Hosmer-May goodness-of-fit test) of each model were compared. Among 7754 patients in the VQI who underwent LEB for critical limb ischemia, the AFS was 74% at 1year. Each of the previously published models for AFS demonstrated similar discriminative performance: c-indices for BASIL, FINNVASC, mPIII were 0.66, 0.60, and 0.64, respectively. The novel VQI-derived model had improved discriminative ability with a c-index of 0.71 and appropriate generalizability on external validation with a c-index of 0.68. The model was well calibrated in both the VQI and PIII data sets (goodness of fit P= not significant). Currently available prediction models for AFS after LEB perform modestly when applied to national contemporary VQI data. Moreover, the performance of each model was inferior to that of the novel VQI-derived model. Because the importance of risk-adjusted outcome reporting continues to increase, national registries such as VQI should begin using this novel model for benchmarking quality of care.

A Comparative Evaluation of Risk Adjustment Models for Benchmarking Amputation-Free Survival After Lower Extremity Bypass

Providing patients and payers with publicly reported risk-adjusted quality metrics for the purpose of benchmarking physicians and institutions has become a national priority. Although several risk-adjustment models have been developed to estimate outcomes after lower extremity bypass (LEB) for critical limb ischemia (CLI), the appropriateness of these models for benchmarking contemporary practice has not been defined. We sought to identify the highest performing risk adjustment model for amputation-free survival (AFS) at 1 year. Using the national Society for Vascular Surgery Vascular Quality Initiative (SVS VQI) database (2003-2012), we assessed the performance of three previously validated risk adjustment models and a novel VQI-derived model for AFS. The Bypass versus Angioplasty in Severe Ischaemia of the Leg (BASIL), FINNVASC, and the modified Project of Ex-vivo vein graft Engineering via Transfection III (mPIII) risk scores were applied to the VQI cohort. The relative performance of each model was compared using the Herrel C index. The novel VQI-derived model was externally validated using the PIII data set. Among 7750 patients in the SVS VQI who underwent LEB for CLI, at 1 year, the AFS was 81%. Each of the existing models for AFS demonstrated similar discriminative performance: the C indices for BASIL, FINNVASC, mPIII were 0.66, 0.60, and 0.64, respectively. The novel VQI-derived model (Table) had improved discriminative ability with a C index of 0.71 and appropriate generalizability on external validation with a C index of 0.68. Currently available prediction models perform modestly when applied to national contemporary VQI data. As the importance of risk adjusted outcome reporting is increasingly recognized, national registries such as VQI should begin using this novel model for benchmarking quality of care.TableDerivation of a novel risk adjustment model in the Vascular Quality Initiative (VQI) data set: Adjusted hazard ratio (HR) with of major amputation or death at 1 year (n = 7318, of which 1092 were heaths or major amputations; C index = 0.71)VariableHR (95% CI)Age, years <60Referent 60-690.90 (0.76-1.07) 70-790.88 (0.74-1.05) ≥801.20 (1.00-1.44)Tissue loss1.33 (1.16-1.53)Congestive heart failure1.33 (1.16-1.53)Diabetes1.22 (1.07-1.40)Renal function Creatinine <1.8 mg/dLReferent Creatinine >1.8 mg/dL1.38 (1.12-1.71) Dialysis dependent2.38 (2.02-2.80)Preoperative functional status IndependentReferent Ambulatory with assistance1.44 (1.25-1.65) Bedridden3.96 (2.47-6.36) Wheelchair2.20 (1.81-2.67) Prosthetic bypass conduit1.87 (1.64-2.12)Distal target Above-knee poplitealReferent Below-knee popliteal target1.31 (1.07-1.60) Tibial/pedal target1.78 (1.48-2.15)Urgent procedures1.39 (1.22-1.58)Weight per 5 kg0.96 (0.94-0.97)Antiplatelet agent upon discharge0.61 (0.53-0.72)CI, Confidence interval. Open table in a new tab

The BASIL survival prediction model in patients with peripheral arterial disease undergoing revascularization in a university hospital setting and comparison with the FINNVASC and modified PREVENT scores

Critical limb ischemia carries a significant risk of morbidity and mortality. The development of scores to predict risk can aid clinical decision making. The Bypass versus Angioplasty in Severe Ischaemia of the Leg (BASIL) trial investigators developed a model to predict death, which has not been previously validated. Data were collected in a prospectively maintained database on all patients who underwent angioplasty or arterial bypass for peripheral artery disease in a university hospital between January 2008 and June 2010. The main outcome measures were all-cause mortality and amputation-free survival at 3, 6, 12, and 24 months after the index intervention. The BASIL survival predictor, Finland National Vascular (FINNVASC) registry, and Edifoligide for the Prevention of Infrainguinal Vein Graft Failure (PREVENT) models were applied and receiver-operating characteristic (ROC) curve analysis was used to evaluate their predictive power. Data on 342 patients were collected. Patients with isolated iliac disease or claudication were excluded. The 6-, 12-, and 24-month all-cause mortality rates were 11.6%, 17.9%, and 26.8%, respectively. The area under the ROC curve (95% confidence interval) using the BASIL score to predict mortality at 6, 12, and 24 months was 0.700 (0.60-0.80; P<.001), 0.651 (0.56-0.74; P<.003), and 0.681 (0.59-0.74; P<.001), respectively. ROC curve analysis indicated that the performance of the BASIL score in this cohort was comparable to other validated predictive scores. The BASIL survival prediction model can moderately predict short-term and medium-term mortality in patients with limb ischemia and may be a useful adjunct to decision making in everyday clinical practice.

Bypass versus Angioplasty in Severe Ischaemia of the Leg (BASIL) trial: An intention-to-treat analysis of amputation-free and overall survival in patients randomized to a bypass surgery-first or a balloon angioplasty-first revascularization strategy

Bypass versus Angioplasty in Severe Ischaemia of the Leg (BASIL) trial: An intention-to-treat analysis of amputation-free and overall survival in patients randomized to a bypass surgery-first or a balloon angioplasty-first revascularization strategy

Bypass versus Angioplasty in Severe Ischaemia of the Leg (BASIL) and the (hoped for) dawn of evidence-based treatment for advanced limb ischemia

The Bypass versus Angioplasty in Severe Ischemia of the Leg (BASIL) trial is the only randomized controlled trial (RCT) to date comparing open surgical bypass with endovascular therapy for severe limb ischemia (SLI). In their initial 2005 publication, the BASIL investigators reported that the main clinical outcomes (overall survival and amputation-free survival) were no different at 2 years after randomization to angioplasty-first or bypass-first revascularization strategies. However, beyond 2 years there appeared to be a benefit for open bypass surgery, providing impetus for an extension study. The final analysis of the long-term outcomes from BASIL is now presented in a set of articles that are reviewed in this commentary. The benefit of initial randomization to open surgery for patients surviving > or =2 years (70% of the BASIL cohort) was confirmed. When outcomes were analyzed by treatment received, patients who had received prosthetic bypass grafts (25% of the surgical arm) fared much more poorly than those treated with a vein bypass. Patients who underwent surgical bypass after an initial failed angioplasty also fared significantly worse than those who were treated initially with bypass surgery. Health-related quality of life measures and costs were not significantly different overall. There are many controversies surrounding the BASIL trial and its interpretation, which are reviewed herein. These include the choice of study population, end points examined, and the nature of procedures performed. The BASIL trial confirms the primacy of open surgical bypass with vein for most patients with SLI and raises questions about the sequelae of failed endovascular interventions. Further multicenter trials are needed to address the large gap in evidence for treatment selection in this patient population.

Bypass versus Angioplasty in Severe Ischaemia of the Leg (BASIL) trial: A survival prediction model to facilitate clinical decision making

An intention-to-treat analysis of the Bypass versus Angioplasty in Severe Ischaemia of the Leg (BASIL) trial showed that in patients with severe lower limb ischemia (SLI) due to infrainguinal disease who survived for 2 years after intervention, initial randomization to a bypass surgery (BSX)-first vs balloon angioplasty (BAP)-first revascularization strategy was associated with improvements in subsequent overall survival (OS) and amputation-free survival (AFS) of about 7 and 6 months, respectively. This study explored the value of baseline factors to estimate the likelihood of survival to 2 years for the trial cohort (Cox model) and for individual BASIL trial patients (Weibull model) as an aid to clinical decision making. Of 452 patients presenting to 27 United Kingdom hospitals, 228 were randomly assigned to a BSX-first and 224 to a BAP-first revascularization strategy. Patients were monitored for at least 3 years. Baseline factors affecting the survival of the entire cohort were examined with a multivariate Cox model. The chances of survival at 1 and 2 years for patients with given baseline characteristics were estimated with a Weibull parametric model. At the end of follow-up, 172 patients (38%) were alive without major limb amputation of the trial leg, and 202 (45%) were alive. Baseline factors that were significant in the Cox model were BASIL randomization stratification group, below knee Bollinger angiogram score, body mass index, age, diabetes, creatinine level, and smoking status. Using these factors to define five equally sized groups, we identified patients with 2-year survival rates of 50% to 90%. The factors that contributed to the Weibull predictive model were age, presence of tissue loss, serum creatinine, number of ankle pressure measurements detectable, maximum ankle pressure measured, a history of myocardial infarction or angina, a history of stroke or transient ischemia attack, below knee Bollinger angiogram score, body mass index, and smoking status. Patients in the BASIL trial were at high risk of amputation and death regardless of revascularization strategy. However, baseline factors can be used to stratify those risks. Furthermore, within a parametric Weibull model, certain of these factors can be used to help predict outcomes for individuals. It may thus be possible to define the clinical and anatomic (angiographic) characteristics of SLI patients who are likely-and not likely-to live for >2 years after intervention. Used appropriately in the context of the BASIL trial outcomes, this may aid clinical decision making regarding a BSX- or BAP-first revascularization strategy in SLI patients like those randomized in BASIL.

Bypass versus Angioplasty in Severe Ischaemia of the Leg (BASIL) trial: An intention-to-treat analysis of amputation-free and overall survival in patients randomized to a bypass surgery-first or a balloon angioplasty-first revascularization strategy

A 2005 interim analysis of the Bypass versus Angioplasty in Severe Ischaemia of the Leg (BASIL) trial showed that in patients with severe lower limb ischemia (SLI; rest pain, ulceration, gangrene) due to infrainguinal disease, bypass surgery (BSX)-first and balloon angioplasty (BAP)-first revascularization strategies led to similar short-term clinical outcomes, although BSX was about one-third more expensive and morbidity was higher. We have monitored patients for a further 2.5 years and now report a final intention-to-treat (ITT) analysis of amputation-free survival (AFS) and overall survival (OS). Of 452 enrolled patients in 27 United Kingdom hospitals, 228 were randomized to a BSX-first and 224 to a BAP-first revascularization strategy. All patients were monitored for 3 years and more than half for >5 years. At the end of follow-up, 250 patients were dead (56%), 168 (38%) were alive without amputation, and 30 (7%) were alive with amputation. Four were lost to follow-up. AFS and OS did not differ between randomized treatments during the follow-up. For those patients surviving 2 years from randomization, however, BSX-first revascularization was associated with a reduced hazard ratio (HR) for subsequent AFS of 0.85 (95% confidence interval [CI], 0.5-1.07; P = .108) and for subsequent OS of 0.61 (95% CI, 0.50-0.75; P = .009) in an adjusted, time-dependent Cox proportional hazards model. For those patients who survived for 2 years after randomization, initial randomization to a BSX-first revascularization strategy was associated with an increase in subsequent restricted mean overall survival of 7.3 months (95% CI, 1.2-13.4 months, P = .02) and an increase in restricted mean AFS of 5.9 months (95% CI, 0.2-12.0 months, P = .06) during the subsequent mean follow-up of 3.1 years (range, 1-5.7 years). Overall, there was no significant difference in AFS or OS between the two strategies. However, for those patients who survived for at least 2 years after randomization, a BSX-first revascularization strategy was associated with a significant increase in subsequent OS and a trend towards improved AFS.

Bypass versus Angioplasty in Severe Ischaemia of the Leg (BASIL) trial: A description of the severity and extent of disease using the Bollinger angiogram scoring method and the TransAtlantic Inter-Society Consensus II classification

The Bypass versus Angioplasty in Severe Ischaemia of the Leg (BASIL) trial showed in patients with severe lower limb ischemia (rest pain, tissue loss) who survive for 2 years after intervention that initial randomization to bypass surgery, compared with balloon angioplasty, was associated with an improvement in subsequent amputation-free survival and overall survival of about 6 and 7 months, respectively. The aim of this report is to describe the angiographic severity and extent of infrainguinal arterial disease in the BASIL trial cohort so that the trial outcomes can be appropriately generalized to other patient cohorts with similar anatomic (angiographic) patterns of disease. Preintervention angiograms were scored using the Bollinger method and the TransAtlantic Inter-Society Consensus (TASC) II classification system by three consultant interventional radiologists and two consultant vascular surgeons unaware of the treatment received or patient outcomes. As was to be expected from the randomization process, patients in the two trial arms were well matched in terms of angiographic severity and extent of disease as documented by Bollinger and TASC II. In patients with the least overall disease, it tended to be concentrated in the superficial femoral and popliteal arteries, which were the commonest sites of disease overall. The below knee arteries became increasingly involved as the overall severity of disease increased, but the disease in the above knee arteries did not tend to worsen. The posterior tibial artery was the most diseased crural artery, whereas the peroneal appeared relatively spared. There was less interobserver disagreement with the Bollinger method than with the TASC II classification system, which also appears inherently less sensitive to clinically important differences in infrapopliteal disease among patients with severe leg ischemia. Anatomic (angiographic) disease description in patients with severe leg ischemia requires a reproducible scoring system that is sensitive to differences in crural artery disease. The Bollinger system appears well suited for this purpose, but the TASC II classification system less so. We hope this detailed analysis will facilitate appropriate generalization of the BASIL trial data to other groups of patients affected by similar anatomic (angiographic) patterns of disease.

Bypass versus Angioplasty in Severe Ischaemia of the Leg (BASIL) trial: Health-related quality of life outcomes, resource utilization, and cost-effectiveness analysis

The Bypass versus Angioplasty in Severe Ischaemia of the Leg (BASIL) trial showed that survival in patients with severe lower limb ischemia (rest pain, tissue loss) who survived postintervention for >2 years after initial randomization to bypass surgery (BSX) vs balloon angioplasty (BAP) was associated with an improvement in subsequent amputation-free and overall survival of about 6 and 7 months, respectively. We now compare the effect on hospital costs and health-related quality of life (HRQOL) of the BSX-first and BAP-first revascularization strategies using a within-trial cost-effectiveness analysis. We measured HRQOL using the Vascular Quality of Life Questionnaire (VascuQol), the Short Form 36 (SF-36), and the EuroQol (EQ-5D) health outcome measure up to 3 years from randomization. Hospital use was measured and valued using United Kingdom National Health Service hospital costs over 3 years. Analysis was by intention-to-treat. Incremental cost-effectiveness ratios were estimated for cost per quality-adjusted life-year (QALY) gained. Uncertainty was assessed using nonparametric bootstrapping of incremental costs and incremental effects. No significant differences in HRQOL emerged when the two treatment strategies were compared. During the first year from randomization, the mean cost of inpatient hospital treatment in patients allocated to BSX ($34,378) was estimated to be about $8469 (95% confidence interval, $2,417-$14,522) greater than that of patients allocated to BAP ($25,909). Owing to increased costs subsequently incurred by the BAP patients, this difference decreased at the end of follow-up to $5521 ($45,322 for BSX vs $39,801 for BAP) and was no longer significant. The incremental cost-effectiveness ratio of a BSX-first strategy was $184,492 per QALY gained. The probability that BSX was more cost-effective than BAP was relatively low given the similar distributions in HRQOL, survival, and hospital costs. Adopting a BSX-first strategy for patients with severe limb ischemia does result in a modest increase in hospital costs, with a small positive but insignificant gain in disease-specific and generic HRQOL. However, the real-world choice between BSX-first and BAP-first revascularization strategies for severe limb ischemia due to infrainguinal disease cannot depend on costs alone and will require a more comprehensive consideration of individual patient preferences conditioned by expectations of survival and other health outcomes.