Endoluminal interventions versus surgical interventions for stenosis in vein grafts following infrainguinal bypass

Francesco E Botelho; Daniel G Cacione; Jose Oyama Leite; Jose CC Baptista-Silva

doi:10.1002/14651858.CD013702.pub2

Intervenciones endoluminales versus intervenciones quirúrgicas para la estenosis en injertos venosos tras una derivación infrainguinal

Authors' declarations of interest

Version published: 28 April 2021 Version history

https://doi.org/10.1002/14651858.CD013702.pub2

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Resumen

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Antecedentes

La cirugía de revascularización con un injerto de vena safena grande, u otro injerto venoso autólogo, es una opción de tratamiento conocida para la enfermedad arterial periférica de las extremidades inferiores, incluida la isquemia crónica con peligro para la extremidad y la claudicación intermitente, los aneurismas periféricos de las extremidades y los traumatismos arteriales importantes de las extremidades. La cirugía de revascularización tiene buenos resultados en cuanto a las tasas de conservación de las extremidades y la permeabilidad del injerto a largo plazo, pero está limitada por la posibilidad de fracaso del injerto venoso debido a estenosis del mismo. La detección de estenosis mediante monitorización clínica y ecográfica, seguida de tratamiento, sirve para evitar la oclusión del injerto. El enfoque convencional para el tratamiento de los pacientes con estenosis del injerto tras una derivación (o bypass) infrainguinal consiste en la reparación quirúrgica abierta, que se suele realizar bajo anestesia general. El tratamiento endoluminal con angioplastia es menos invasivo y utiliza anestesia local. Ambos métodos tienen como objetivo mejorar el flujo sanguíneo de la extremidad.

Objetivos

Evaluar la efectividad de las intervenciones endoluminales versus la intervención quirúrgica para las personas con estenosis del injerto venoso tras un bypass infrainguinal.

Métodos de búsqueda

El documentalista del Grupo Cochrane Vascular (Cochrane Vascular) buscó en el Registro especializado del Grupo, el Registro Cochrane central de ensayos controlados (Cochrane Central Register of Controlled Trials; CENTRAL), en MEDLINE, Embase, CINAHL, AMED, la Plataforma de registros internacionales de ensayos clínicos de la Organización Mundial de la Salud y en ClinicalTrials.gov hasta el 25 de agosto de 2020.

Criterios de selección

El objetivo fue incluir todos los ensayos controlados aleatorizados (ECA) publicados y no publicados que compararon intervenciones endoluminales versus intervención quirúrgica para las personas con estenosis del injerto venoso tras una derivación infrainguinal.

Obtención y análisis de los datos

Dos autores de la revisión evaluaron de forma independiente todos los estudios identificados para su posible inclusión en la revisión. Se utilizaron los procedimientos metodológicos estándar según el Manual Cochrane de revisiones sistemáticas de intervenciones (Cochrane Handbook for Systematic Review of Interventions). Los desenlaces principales de interés fueron la permeabilidad primaria, la permeabilidad primaria asistida y la mortalidad por todas las causas.

Resultados principales

No se identificaron ECA que cumplieran los criterios de inclusión para esta revisión.

Conclusiones de los autores

No se encontraron ECA que compararan intervenciones endoluminales con la intervención quirúrgica para la estenosis en injertos venosos tras una derivación infrainguinal. En la actualidad no hay evidencia de certeza alta que apoye el uso de un tipo de intervención sobre otro. Se necesitan estudios de alta calidad para aportar evidencia sobre el tratamiento de la estenosis de los injertos venosos tras el bypass infrainguinal.

PICOs

Population

Intervention

Comparison

Outcome

The PICO model is widely used and taught in evidence-based health care as a strategy for formulating questions and search strategies and for characterizing clinical studies or meta-analyses. PICO stands for four different potential components of a clinical question: Patient, Population or Problem; Intervention; Comparison; Outcome.

See more on using PICO in the Cochrane Handbook.

Resumen en términos sencillos

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Tratamiento endoluminal (a través de los vasos sanguíneos) o con cirugía abierta para prevenir la obstrucción de los injertos venosos tras el tratamiento de revascularización para la enfermedad arterial periférica con riesgo para las extremidades

Antecedentes

La cirugía de revascularización (o bypass, es decir, tomar una vena de la misma pierna o de la opuesta [injerto] y utilizarla para llevar la sangre desde arriba hacia abajo de la arteria bloqueada, dañada o dilatada) es un procedimiento quirúrgico que se suele utilizar para tratar la enfermedad arterial periférica sintomática de las extremidades inferiores (enfermedad en la que los vasos sanguíneos están estrechados u obstruidos), el aneurisma de las extremidades inferiores (expansión de los vasos sanguíneos como un globo) y los traumatismos vasculares importantes de las extremidades inferiores. Se trata de una opción de tratamiento conocida, con excelentes resultados en cuanto a la conservación de la extremidad y la durabilidad del injerto, pero el injerto puede desarrollar un estrechamiento (estenosis), que puede comprometer su función. Existen dos opciones para tratar estas estenosis antes de la oclusión del bypass venoso: la intervención quirúrgica abierta y las intervenciones endoluminales. Las intervenciones quirúrgicas abiertas tienen una larga perdurabilidad, pero son procedimientos invasivos. Dichas intervenciones pueden dar lugar a complicaciones posoperatorias de la herida. Los tratamientos endoluminales son menos invasivos. Estos tratamientos se podrían asociar con menos complicaciones posoperatorias, pero podrían tener menos perdurabilidad en comparación con el tratamiento quirúrgico abierto. Esta revisión se realizó para investigar si es mejor una intervención abierta o endoluminal para tratar la estenosis en el bypass de injerto venoso.

Características de los estudios y resultados clave

Se buscó evidencia que comparara directamente las intervenciones endoluminales con la intervención quirúrgica abierta para la estenosis en los injertos venosos tras una revascularización infrainguinal (hasta el 25 de agosto de 2020). No se encontraron ensayos controlados aleatorizados (estudios clínicos en los que las personas se dividen al azar en dos o más grupos de tratamiento) sobre este tema. Es necesario seguir investigando para ayudar a los cirujanos vasculares y endovasculares y a sus pacientes a elegir la mejor opción para el tratamiento de la estenosis del injerto venoso tras el bypass de la pierna.

Fiabilidad de la evidencia

No se encontraron estudios, por lo que no fue posible evaluar evidencia.

Conclusión

No se encontraron ECA que compararan las intervenciones endoluminales con la intervención quirúrgica para la estenosis de injertos venosos tras la revascularización de la pierna. Se necesitan estudios de alta calidad que aporten evidencia sobre el tratamiento de la estenosis del injerto venoso tras la revascularización infrainguinal.

Authors' conclusions

Implications for practice

We found no RCTs that compared endoluminal interventions versus surgical intervention for stenosis in vein grafts following infrainguinal bypass. Currently, no high‐certainty evidence is available to support the use of one type of intervention over another (endoluminal versus open surgical). Until RCT evidence is available, selection of strategies for treatment of vein graft stenosis will likely be guided by other sources of information, such as registries, reviews of cohort studies and case series, and society guidelines.

Implications for research

High‐quality, adequately powered RCTs are needed to compare endoluminal interventions versus surgical intervention for treatment of patients with stenosis in vein grafts following infrainguinal bypass. The most important outcomes to be measured are primary and primary assisted patency and all‐cause mortality. Other important issues to be considered are limb salvage, technical success, length of hospital stay, and quality of life. In addition to selected outcomes from this review, a cost analysis should be considered as an outcome in future studies.

Background

Description of the condition

Peripheral arterial disease (PAD) of the lower limbs affects 3% of the general population and 12% of the population over 70 years old (Fowkes 2013). One of the most severe clinical presentations is chronic limb‐threatening ischaemia (CLTI), which threatens the lower limb due to restriction in blood flow, with symptoms of ischaemic rest pain and skin lesions (Mills 2014). Between 500 and 1000 new cases of CLTI per million people are reported every year in Europe and North America (Norgren 2007). Nehler 2014 estimated CLTI incidence to range from 0.02% to 0.35%, and prevalence from 1.2% to 2.35%, across studies of large, geographically diverse national populations.

Bypass surgery using a large saphenous vein graft, or another autologous venous graft, is a well‐recognised treatment option for managing PAD of the lower limbs, including CLTI and intermittent claudication, peripheral limb aneurysms, and major limb arterial trauma (Antoniou 2017).

Bypass surgery with vein graft is limited by the possibility of vein graft failure. The three phases of vein graft failure are categorised according to the timing of failure: early (less than 30 days), intermediate (ranging from 30 days to one year), and late (longer than one year). Early graft failures generally occur within the first 48 hours and are a consequence of technical problems, such as poor anastomosis and poor graft quality; reduced inflow or outflow; and hypercoagulability. Late failures are a consequence of progression of atherosclerotic disease that affects inflow and outflow vessels of the bypass graft.

Intermediate failures are a consequence of stenoses that develop in proximal and distal anastomoses and along the body of the graft. These stenoses are a manifestation of myointimal hyperplasia (Davies 1995). This occurs mainly in the first year after revascularisation as the result of proliferation and migration of smooth muscle cells from the middle layer to the intima layer of the vein. It is stimulated by factors derived from fibroblasts and platelets in response to manipulation of the graft and their use in haemodynamic conditions that differ from the original venous circulation. Although myointimal hyperplasia is seen in 40% of venous grafts, there is no evidence to suggest that medical treatment can prevent onset (Wallitt 2007).

Detection of stenoses through clinical and ultrasonographic surveillance (Mofidi 2017; Patel 2016), followed by treatment, is used to avoid graft occlusion. Vein graft stenosis can be associated with a decrease in the ankle brachial index (ABI). However, such a decrease may not be noticeable in patients with calcified tibial arteries, as calcified tibial arteries may make the ABI insensitive to detecting haemodynamically significant vein graft stenosis.

Vein graft stenosis is initially detected by clinical and ultrasonographic examination (Mofidi 2017). Ultrasonographic monitoring of venous grafts can detect a stenosis (and its location and extension along the graft) by focal increase in systolic peak velocity (Mofidi 2017). The accuracy of duplex ultrasound (DUS) for graft surveillance after peripheral arterial bypass grafting using autologous veins is evaluated in Chappell 2014. Improvements in duplex ultrasound scanning technology have allowed the detection of stenoses that impair graft patency (Davies 2005); secondary interventions are needed to avoid graft failure in about 30% to 50% of grafts (Patel 2016).

Lower limb revascularisation can be performed with prosthetic grafts, which are also subject to development of graft‐threatening stenosis at anastomotic sites. However, as the mechanism of stenosis of prosthetic grafts is different from that of stenosis of vein grafts, we do not include prosthetic grafts in this review.

Description of the intervention

The conventional approach to treatment of patients with graft stenosis following infrainguinal bypass consists of open surgical repair with direct approach to the graft, which is performed under general anaesthesia. The graft stenosis may be bypassed with a short interposition vein graft (jump), or a patch angioplasty may be performed over the area of stenosis, resulting in improved blood flow (Berceli 2009).

Endoluminal treatment with angioplasty uses local anaesthesia and is a less invasive approach. Endoluminal treatment of graft stenosis is usually performed through contralateral access to the femoral artery. Angiography of the bypass and outflow/inflow vessels is performed to visualise the location of the blockage. The graft stenosis is detected and is traversed by a guidewire, followed by balloon angioplasty with a diameter similar to the adjacent vein graft; this also aims to improve blood flow (Berceli 2009).

How the intervention might work

Open surgical repair of infrainguinal vein bypass stenosis has been shown to result in satisfactory immediate and long‐term results, probably with a lower rate of recurrence than endoluminal treatment: open surgical repair has resulted in five‐year primary and secondary patency of 42% to 60% and 76% to 90%, respectively (Nguyen 2004). However, this approach has drawbacks: an additional conduit is required, dissection through scar tissue is performed, and surgical wound healing may delay recovery (with increased length of hospital stay and treatment costs). It is also associated with costs due to hospitalisation and additional treatment for possible complications in debilitated people with comorbidities (Berceli 2007; Kreienberg 2007).

Endoluminal treatment of patients with infrainguinal vein graft stenosis is a less invasive approach that can potentially reduce surgical morbidity (Alexander 2003). However, it may be limited by recurrence of stenoses. Endoluminal repair of vein graft stenosis has been reported to lead to three‐year primary patency of 22% to 38%, increasing the need for multiple repeat procedures (Guntani 2019; Mathur 2016). This has a subsequent impact on the person's quality of life, and it incurs additional costs (Berceli 2007).

Why it is important to do this review

Observational studies that use angioplasty for treatment of patients with venous graft stenosis show promising results in terms of technical success and reduced morbidity (Berceli 2009). However, long‐term patency and how angioplasty compares with conventional surgical treatment remain unknown. In addition, data on the best treatment for vein graft stenosis are lacking. No systematic reviews on this topic have yet been published. This systematic review aimed to compare endoluminal interventions versus surgical intervention for stenosis in infrainguinal vein grafts. We planned to present available evidence to inform healthcare decisions for management of stenosis after infrainguinal bypass.

Objectives

To assess the effectiveness of endoluminal interventions versus surgical intervention for people with vein graft stenosis following infrainguinal bypass.

Methods

Criteria for considering studies for this review

Types of studies

We planned to include randomised controlled trials (RCTs) and quasi‐RCTs that compare use of endoluminal interventions versus surgical intervention for treating patients with stenosis in infrainguinal vein grafts. We defined quasi‐RCTs as trials in which allocation methods are not completely random, for example, using alternation such as by date of birth or by day of the week.

Types of participants

We planned to include participants undergoing endoluminal or surgical interventions to manage stenosis in infrainguinal vein grafts following infrainguinal bypass for treatment of chronic limb‐threatening ischaemia (CLTI), intermittent claudication, aneurysm, or trauma.

Types of interventions

We planned to include studies that compare any endoluminal interventions (including plain balloon angioplasty (POBA), drug‐coated balloon angioplasty (DCB), bare metal stent with angioplasty, drug eluting stent (DES), and cutting balloon angioplasty) with any surgical intervention (including patch angioplasty and jump graft interposition) for stenosis in infrainguinal vein grafts (proximal and distal anastomosis and the graft itself).

Our comparisons of interest were:

POBA versus patch angioplasty;
POBA versus jump graft interposition;
DCB angioplasty versus patch angioplasty;
DCB angioplasty versus jump graft interposition;
bare metal stent versus patch angioplasty;
bare metal stent versus jump graft interposition;
DES versus patch angioplasty;
DES versus jump graft interposition;
cutting balloon angioplasty versus patch angioplasty; and
cutting balloon angioplasty versus jump graft interposition.

Types of outcome measures

Primary outcomes

Primary patency (defined as a patent graft without the need for re‐intervention, as assessed by angiography or ultrasonography) at 30 days, at one year, and longer when possible
Primary assisted patency (defined as the need for revision or further revascularisation interventions to prevent impending occlusion or progression of stenosis, as assessed by angiography or ultrasonography) at 30 days, at one year, and longer when possible
All‐cause mortality (at 30 days, at one year, and longer when possible)

Secondary outcomes

Limb salvage at 30 days, at one year, and longer when possible
Technical success (defined as technical accomplishment of the intended intervention)
Re‐intervention (need for re‐intervention due to complications following the procedure, i.e. bleeding, infection, etc.)
Quality of life (QoL), as reported on validated scales such as the Short Form 36‐Item Questionnaire (SF‐36) and the European Quality of Life Questionnaire (EQ‐5D) for general QoL assessments, and the Vascular Quality of Life Questionnaire for disease‐specific QoL assessment (Alabi 2017)
Length of hospital stay

Search methods for identification of studies

We used no restrictions on language or publication status (published, unpublished, in press, or in progress).

Electronic searches

The Cochrane Vascular Information Specialist conducted systematic searches of the following databases for relevant trials.

Cochrane Vascular Specialised Register via Cochrane Register of Studies (CRS Web searched to 25 August 2020).
Cochrane Central Register of Controlled Trials (CENTRAL) via Cochrane Register of Studies Online (CRSO 2020, Issue 7).
MEDLINE (Ovid MEDLINE Epub Ahead of Print, In‐Process & Other Non‐Indexed Citations, Ovid MEDLINE Daily, and Ovid MEDLINE) (searched to 25 August 2020).
Embase Ovid (searched to 25 August 2020).
Cumulative Index to Nursing and Allied Health Literature (CINAHL EBSCO) (searched to 25 August 2020).

The Information Specialist modelled search strategies for other databases on the search strategy designed for CENTRAL. When appropriate, these searches were combined with adaptations of the highly sensitive search strategy designed by Cochrane for identifying RCTs and controlled clinical trials (as described in the Cochrane Handbook for Systematic Reviews of Interventions, Chapter 6; Lefebvre 2011). Search strategies for major databases are provided in Appendix 1.

The Information Specialist searched the following trial registries on 25 August 2020.

World Health Organization International Clinical Trials Registry Platform (who.int/trialsearch).
ClinicalTrials.gov (clinicaltrials.gov).

Searching other resources

We planned to examine the bibliographies of study reports identified in our search to identify other relevant articles. We planned to contact the authors of relevant articles by email to request data and to identify other unpublished RCTs, but we identified no studies for inclusion.

Data collection and analysis

Selection of studies

Two review authors (FB, DGC) independently evaluated trials for inclusion in this review using the software Covidence (covidence.org). There was no disagreement between the first two review authors. If necessary, disagreements would have been resolved by discussion with a third review author (JCBS). The inclusion criteria that we used to determine suitability are outlined in the section Criteria for considering studies for this review. We illustrated the study selection process in a PRISMA diagram (Liberati 2009).

Data extraction and management

We planned that two review authors (FB, DGC) would independently extract relevant data from the included studies. We intended to consult a third review author (JCBS) to cross‐check the data. We intended to collect the following information for each included study.

Methods (study design; numbers of participants, exclusions, losses to follow‐up; intention‐to‐treat analysis; duration; dates).
Participant demographics (country, setting, age, gender, inclusion and exclusion criteria).
Interventions and comparisons (intervention and control group sample sizes, anaesthetic, technique details).
Outcomes (as specified in the section Criteria for considering studies for this review).
Funding source and declaration of interest by study authors.

Assessment of risk of bias in included studies

We planned that two review authors (FB, DGC) would independently perform a thorough 'Risk of bias' assessment of all included studies, using Cochrane's 'Risk of bias' tool (Higgins 2011). This tool assesses random sequence generation, allocation concealment methods, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, selective outcome reporting, and any other potential biases, with each domain receiving a rating of high, low, or unclear risk of bias. If needed, a third review author (JCBS) intended to adjudicate disagreements. We planned to contact study authors if we required any clarification to assess risk of bias.

Measures of treatment effect

We planned to measure treatment effect using the risk ratio (RR) for dichotomous data and the mean difference (MD) for continuous data with the same scale. We planned to use the standardised mean difference (SMD) for continuous data with different scales. We planned to report 95% confidence intervals (CIs) for all measures of treatment effect.

Unit of analysis issues

We planned to use the individual limb as the unit of analysis for the outcomes graft patency and limb salvage. We planned to use the individual participant as the unit of analysis for the outcomes mortality, re‐intervention, quality of life, and length of hospital stay.

Dealing with missing data

We planned to contact study authors to enquire about missing or incomplete data. In the event that an included study had a significant quantity of missing data (i.e. more than 20% of data are missing) and attempts to contact the study authors were unsuccessful, we planned to conduct a sensitivity analysis to assess the impact of including such studies in the meta‐analysis. When it was possible, we planned to carry out analyses using the intention‐to‐treat (ITT) principle. We planned to use per‐protocol data if ITT data were not available.

Assessment of heterogeneity

We planned to assess the clinical heterogeneity of studies by confirming whether study participants, interventions, and outcome measures are comparable. In particular, we planned to assess participant demographics, varieties of the type of bypass conduit, location, and features of stenosis in each study. If the 'case mix' were comparable between studies, we planned to proceed to a formal meta‐analysis. We planned to assess statistical heterogeneity by using forest plots, the Chi² test, and the I² statistic (Higgins 2011). Initially, we planned to assess the forest plots of all studies for each outcome to ensure there was overlap of the CIs of effect estimates. If no overlap existed, we planned to further assess the causes of heterogeneity, as it might be inappropriate to proceed with meta‐analysis. We also planned to utilise the I² statistic to assess heterogeneity, and we planned to judge a value of 50% or greater as indicating substantial heterogeneity. In the context of the Chi² test, we planned to use a P value of 0.10 or less to indicate significant heterogeneity.

Assessment of reporting biases

We planned to construct a funnel plot to assess publication bias if 10 or more studies were available for a particular outcome (Sterne 2011).

Data synthesis

We planned to carry out meta‐analyses when the included trials were similar enough to allow meaningful conclusions from a statistically pooled result. We planned to use a random‐effects model for all analyses because we expected some inter‐study variation, and we wished to generalise the study results beyond the specific studies included in the analyses. We planned to calculate 95% CIs for continuous and dichotomous outcome variables, as detailed above. We planned to create a forest plot for each treatment effect. We planned to report data narratively if it was not appropriate to combine them in a meta‐analysis. We planned to conduct statistical analysis to comply with the standard methods of Cochrane Vascular. We planned to use RevMan Web 2019 to perform all statistical analyses and to generate figures.

Subgroup analysis and investigation of heterogeneity

We planned to carry out subgroup analyses by stratifying participants according to the following factors.

Age < 65 and ≥ 65 years.
Gender.
Comorbidities (diabetes versus no diabetes; smokers versus former smokers versus non‐smokers; previous interventions versus no previous interventions).
Stenosis location (proximal anastomosis, body of graft, distal anastomosis).
Features of stenosis (length, early/late, number).
Indication of revascularisation (CLTI, aneurysm, intermittent claudication, trauma).
Localisation of distal anastomosis (above‐knee popliteal, below‐knee popliteal, tibial arteries).
Type of vein graft used (great saphenous vein, arm vein, composite vein).

Sensitivity analysis

We planned to use sensitivity analysis to investigate the robustness of study results. We planned to explore the impact of trials at high risk of bias on the magnitude or direction of overall effect by excluding from the analysis trials at high risk of bias. We planned to define studies to be at high risk of bias if we assessed one or more 'Risk of bias' domains to be at high risk. As described above, we also planned to perform a sensitivity analysis to assess the impact of including in the meta‐analysis studies that had more than 20% missing data when attempts to contact the study authors were unsuccessful. We planned to perform sensitivity analysis for all outcomes, if data were available.

Summary of findings and assessment of the certainty of the evidence

We planned to prepare a 'Summary of findings' table using the GRADEpro Guideline Development Tool to present the main findings of the review for the time point at which the most relevant data were available from the included studies (Atkins 2004; GRADEpro GDT). We planned that the population would consist of participants with stenosis in infrainguinal vein grafts following infrainguinal bypass, and we planned to compare endoluminal versus surgical interventions for treatment of patients with stenosis in infrainguinal vein grafts. We planned to include the main outcomes listed under Types of outcome measures that we considered essential for decision‐making. We planned to evaluate the certainty of the evidence using the GRADE approach (Atkins 2004). We planned to assign one of four levels of certainty ‐ high, moderate, low, or very low ‐ based on overall risk of bias, directness of evidence, inconsistency of results, precision of estimates, and risk of publication bias, as previously described (Higgins 2011). We have included an example 'Summary of findings' table for 'Endoluminal interventions versus surgical intervention for stenosis in infrainguinal vein grafts' (Table 1).

Open in table viewer

Table 1. Draft Summary of findings table: are endoluminal interventions an effective treatment for stenosis in infrainguinal vein grafts?

Endoluminal interventions versus surgical interventions for stenosis in vein grafts following infrainguinal bypass
Patient or population: people with stenosis in infrainguinal vein grafts following infrainguinal bypass Settings: hospital Intervention: endoluminal interventions Comparison: surgical interventions
Outcomes	Anticipated absolute effects*		Relative effect (95% CI)	No. of participants (studies)	Certainty of the evidence (GRADE)	Comments
Outcomes	Risk with surgical interventions	Risk with endoluminal interventions	Relative effect (95% CI)	No. of participants (studies)	Certainty of the evidence (GRADE)	Comments
Primary patency (follow‐up)	Study population		RR (value) ((value) to (value))	(value) ((value))	⊕⊝⊝⊝ very low ⊕⊕⊝⊝ low ⊕⊕⊕⊝ moderate ⊕⊕⊕⊕ high
Primary patency (follow‐up)	(value) per 1000	(value) per 1000 ((value) to (value))	RR (value) ((value) to (value))	(value) ((value))	⊕⊝⊝⊝ very low ⊕⊕⊝⊝ low ⊕⊕⊕⊝ moderate ⊕⊕⊕⊕ high
Primary assisted patency (follow‐up)	Study population		RR (value) ((value) to (value))	(value) ((value))	⊕⊝⊝⊝ very low ⊕⊕⊝⊝ low ⊕⊕⊕⊝ moderate ⊕⊕⊕⊕ high
Primary assisted patency (follow‐up)	(value) per 1000	(value) per 1000 ((value) to (value))	RR (value) ((value) to (value))	(value) ((value))	⊕⊝⊝⊝ very low ⊕⊕⊝⊝ low ⊕⊕⊕⊝ moderate ⊕⊕⊕⊕ high
All‐cause mortality (follow‐up)	Study population		RR (value) ((value) to (value))	(value) ((value))	⊕⊝⊝⊝ very low ⊕⊕⊝⊝ low ⊕⊕⊕⊝ moderate ⊕⊕⊕⊕ high
All‐cause mortality (follow‐up)	(value) per 1000	(value) per 1000 ((value) to (value))	RR (value) ((value) to (value))	(value) ((value))	⊕⊝⊝⊝ very low ⊕⊕⊝⊝ low ⊕⊕⊕⊝ moderate ⊕⊕⊕⊕ high
Limb salvage (follow‐up)	Study population		RR (value) ((value) to (value))	(value) ((value))	⊕⊝⊝⊝ very low ⊕⊕⊝⊝ low ⊕⊕⊕⊝ moderate ⊕⊕⊕⊕ high
Limb salvage (follow‐up)	(value) per 1000	(value) per 1000 ((value) to (value))	RR (value) ((value) to (value))	(value) ((value))	⊕⊝⊝⊝ very low ⊕⊕⊝⊝ low ⊕⊕⊕⊝ moderate ⊕⊕⊕⊕ high
Re‐intervention due to complications (follow‐up)	Study population		RR (value) ((value) to (value))	(value) ((value))	⊕⊝⊝⊝ very low ⊕⊕⊝⊝ low ⊕⊕⊕⊝ moderate ⊕⊕⊕⊕ high
Re‐intervention due to complications (follow‐up)	(value) per 1000	(value) per 1000 ((value) to (value))	RR (value) ((value) to (value))	(value) ((value))	⊕⊝⊝⊝ very low ⊕⊕⊝⊝ low ⊕⊕⊕⊝ moderate ⊕⊕⊕⊕ high
QoL (follow‐up)	Mean (outcome) ranged across control groups from (value) (measure)	Mean (outcome) in intervention groups was (value) (lower/higher) ((value to value lower/higher))		(value) ((value))	⊕⊝⊝⊝ very low ⊕⊕⊝⊝ low ⊕⊕⊕⊝ moderate ⊕⊕⊕⊕ high
Length of hospital stay (follow‐up)	Mean (outcome) ranged across control groups from (value) (measure)	Mean (outcome) in intervention groups was (value) (lower/higher) ((value to value lower/higher))		(value) ((value))	⊕⊝⊝⊝ very low ⊕⊕⊝⊝ low ⊕⊕⊕⊝ moderate ⊕⊕⊕⊕ high
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; QoL: quality of life; RR: risk ratio.
GRADE Working Group grades of evidence. High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.

Results

Description of studies

See Figure 1.

Figure 1

Results of the search

We identified a total of 2011 articles through database searches. Following de‐duplication, we screened 1504 articles and assessed them as not relevant for this review because they were not RCTs, or because they did not compare the specific types of interventions that we had planned to assess. See Figure 1.

Included studies

We found no studies that met the inclusion criteria.