Femoro-popliteaal: Endovasculaire behandeling versus bypasschirurgie

Beoordeeld: 01-04-2025

Uitgangsvraag

Wat is de aanbevolen behandeling van het femoro-politeale traject (endovasculair versus bypass)?

De uitgangsvraag bevat de volgende deelvragen:

Wat is de waarde van endovasculaire behandeling bij patiënten met claudicatio intermittens?
Wat is de waarde van endovasculaire behandeling bij patiënten met kritieke ischemie?

Aanbeveling

Kritieke ischemie:

Overweeg bij kwetsbare oudere patiënten met kritieke ischemie een endovasculaire behandeling van het femoro-popliteale traject.

Overweeg bij een patiënt met kritieke ischemie en een levensverwachting van minimaal twee jaar een revascularisatie van het femoro-popliteale traject middels een chirurgische bypass.

Claudicatio intermittens:

Bepaal samen met een patiënt met claudicatio intermittens de keuze voor endovasculaire of een chirurgische behandeling.

Overwegingen

Voor- en nadelen van de interventie en de kwaliteit van het bewijs

Er is literatuuronderzoek uitgevoerd naar het effect van endovasculaire behandeling met een dotterbehandeling met of zonder stent in vergelijking met een chirurgische bypass bij patiënten met kritieke ischemie en perifeer vaatlijden aan het femoro-popliteale traject (PICO 1) en bij patiënten met claudicatio intermittens in hetzelfde traject (PICO 2). Mortaliteit en patency werden gedefinieerd als cruciale uitkomstmaten voor PICO 1. Voor PICO 2 werd patency als cruciale uitkomstmaat gedefinieerd. Vrij blijven van binaire restenose, re-interventie op basis van symptomatische restenose, amputatie, technisch succes, kwaliteit van leven en wondgenezing werden als belangrijke uitkomstmaten gedefinieerd.

Er werden zeven RCTs geïncludeerd in de literatuuranalyse, waarvan vier studies voldeden aan de inclusiecriteria van PICO 1 en drie studies aan de inclusiecriteria van PICO 2 voldeden. Er werden voor PICO 1 klinisch relevant verschillen gevonden in het voordeel voor endovasculaire behandeling voor de cruciale uitkomstmaat mortaliteit en voor de belangrijke uitkomstmaat re-interventies in het voordeel van een chirurgische bypass bij patiënten met kritieke ischemie. PICO 2 liet voor geen enkele uitkomstmaat een klinisch relevant verschil zien tussen endovasculaire behandeling en een chirurgische bypass behandeling voor patiënten met claudicatio intermittens. De studies lieten voor beide PICO’s geen klinisch relevant verschil zien voor de andere cruciale en belangrijke uitkomstmaten. Daarbij dient het gevonden klinisch relevante verschil voor de cruciale uitkomstmaat mortaliteit voor PICO 1 voorzichtig geïnterpreteerd te worden, aangezien de bewijskracht werd gegradeerd op zeer laag. De zeer lage bewijskracht is met name te wijten aan het mogelijk risico op bias en het kleine aantal events, wat resulteerde in een breed betrouwbaarheidsinterval. Een zeer lage bewijskracht betekent dat de literatuur zeer onzeker is of het gevonden effect het daadwerkelijke effect juist weerspiegelt.

Indien het een kwetsbare oudere patiënt met kritieke ischemie betreft, heeft een minimaal invasieve (endovasculaire) behandeling de voorkeur. Bij jongere patiënten met kritieke ischemie, staat duurzaamheid en patency meer op de voorgrond en is het logischer een veneuze bypass te overwegen in het geval van kritieke ischemie. Uiteraard dient de kwaliteit van leven ook in beschouwing te worden genomen en zal samen beslissenmet de patiënt met duidelijke uiteenzetting van voordelen en nadelen van beide behandelingen uiteindelijk de doorslag geven. Bij patiënten met claudicatioklachten dient uiteraard dezelfde afweging gemaakt te worden, waarbij over het algemeen nog kritischer gekeken moet worden naar het gebruik van bypasschirurgie bij deze groep patiënten. Bij korte laesies in femoro-popliteale traject dient endovasculaire behandeling na falen van conservatieve behandeling (gesuperviseerde looptraining, aerobe training, krachttraining of andere (pijnvrije) beweegvormen) overwogen te worden.

In het geval van kritieke ischemie en met name bij patiënten met wonden heeft revascularisatie de voorkeur, aangezien het genezen van een wond of voorkomen van amputatie uitgebreide gevolgen heeft voor patiënt en naasten. Het nadeel van trials is uiteraard dat er slechts een fractie van de patiënten wordt geïncludeerd, hetgeen kan resulteren in een versimpeling van de daadwerkelijke situatie. Bij de jongere patiënt kan het hebben van claudicatioklachten ook ernstige gevolgen hebben met betrekking tot het uitvoeren van werkzaamheden en soms zelfs verlies van werk. Derhalve blijft het altijd een overweging op basis van bovengenoemd samen beslissen met de patiënt ten aanzien van interventie of niet. Dit in samenhang met zorgprofessionals binnen en buiten het ziekenhuis.

Waarden en voorkeuren van patiënten (en evt. hun verzorgers)

Het verlies van een been kan zeer veel impact hebben en soms leiden tot volledig zorgafhankelijkheid en verlies van zelfstandigheid. Voor patiënten en hun verzorgers kunnen het belangrijkste doel van een interventie het verminderen van pijn, verbeteren van mobiliteit en kwaliteit van leven en het voorkomen van een amputatie zijn. Voor familie en verzorgende kan ook het doel zijn de zelfstandigheid van de patiënt te behouden of verbeteren en daarmee de zorglast te verminderen. Patiënten kunnen een verschil in waarde hebben en voor- en/of nadelen verschillend bekijken. Sommigen zullen bereid zijn een groter risico op complicaties te accepteren als dit betekent dat ze een grotere kans hebben om mobiliteit en zelfstandigheid te behouden. Andere patiënten geven de voorkeur aan een minder invasieve behandeling om het risico op korte termijn complicaties te verminderen, ook indien ze in de toekomst eventueel aanvullende procedures nodig zullen hebben. De waarden en voorkeuren kunnen verschillen per subgroep. Bijvoorbeeld jongere patiënten kunnen de voorkeur hebben voor een meer duurzame oplossing zoals een bypass, terwijl oudere of meer kwetsbare patiënten minder invasieve endovasculaire behandeling kunnen prefereren om de herstelperiode en risico op complicaties te verminderen.

Kosten (middelenbeslag)

Uiteraard dienen de kosten van devices en ziekenhuisopname in overweging te worden genomen. Het is de vraag of de gunstige effecten de extra middelen waard zijn. De analyse hiervan zou de interventie zelf moeten omvatten, alsmede de lange termijn kosten en maatschappelijke kosten die verbonden zijn aan nazorg, mogelijke complicaties en re-interventies. Dit zou naast de kosten geassocieerd met kwaliteitsgecorrigeerde levensjaren (QALY’s) ook andere maatschappelijke en gezondheidskosten dienen te omvatten. De kwaliteit van dit soort onderzoek hangt uiteraard af van de kwaliteit van de gegevens alsmede maatschappelijke kosten en de relevantie van de context waarin de studie is uitgevoerd. Deze analyse zal anders zijn bij patiënten met claudicatioklachten in vergelijking met patiënten met kritieke ischemie. Er kunnen patiënten zijn waarbij de kosten andere argumenten zullen laten gelden. Bij patiënten met een lage kans op succesvolle duurzame endovasculaire behandeling, zou eventueel de chirurgische bypass een betere optie kunnen zijn. Gepaard gaande met initiële hoge kosten, echter op langere termijn kosten effectiever. Bij patiënten met slechtere gezondheid en meer comorbiditeit zou een endovasculaire behandeling de voorkeur kunnen hebben ondanks hogere reinterventie kans. Uiteraard blijft het belangrijk dat behandelteams, patiënten en familie/verzorgers middels samen beslissen duidelijk communiceren over de wens van de patiënt. Zodat in het besluitvormingsproces wordt geborgd dat de gekozen behandeling past bij de persoonlijke waarden en voorkeuren van de patiënt.

Aanvaardbaarheid, haalbaarheid en implementatie

In Nederland is er geen landelijke registratie die de behandelingen van perifeer vaatlijden structureel evalueert, zoals dit wel het geval is bij behandelingen van het abdominaal aorta aneurysma of bij carotischirurgie. Derhalve is een goed en gedegen antwoord hierover moeilijk, het is echter wel zo dat in Nederland conform de huidige Europese richtlijnen patiënten behandeld worden en endovasculaire technieken evenals open bypasschirurgie en hybride beiden als goed onderwezen technieken worden gezien en bekend zijn in Nederland. Deze huidige richtlijn is conform de Europese richtlijn zoals recent gepubliceerd en staat niet ver af van de dagelijkse praktijk, derhalve zijn de aanbevelingen niet tegenstrijdig met huidige praktijk, waar gezien de evidence (of gebrek aan evidence) ook veel ruimte is voor de voorkeur van de patiënt in samenspraak met zijn/haar behandelaar. De invloed van een interventie op gezondheidsongelijkheid is complex en wordt beïnvloed door vele factoren, waaronder toegang tot zorg, culturele en taalbarrières en socio-economische status. De toegang tot ons gezondheidsstelsel is groot, maar bovengenoemde factoren kunnen ondanks hun kleine rol echter wel leiden tot discrepanties.

Op dit moment worden geen belemmerende factoren voor implementatie voorzien, dit zou eventueel door vergrijzing op termijn een steeds groter probleem kunnen worden en verdient in de toekomst zeker de aandacht. De haalbaarheid van een interventie kan afhangen van de infrastructuur van de zorginstelling en beschikbaarheid van zorgverleners en middelen.

Rationale van de aanbeveling: weging van argumenten voor en tegen de interventies

Bij patiënten met perifeer arterieel vaatlijden is het de uitdaging de juiste behandeling te kiezen niet alleen gebaseerd op klinische gegevens, maar ook op basis van de patiënt en zijn/haar voorkeuren. De beslissing tussen endovasculaire behandeling of chirurgische bypass hangt af van verschillende factoren zoals leeftijd, comorbiditeit, ernst van de ziekte (claudicatio intermittens versus kritieke ischemie) en de potentieel levens veranderende impact van de behandeling op de patiënt. De huidige literatuur biedt enige richting, echter kwaliteit en interpretatie van de huidige evidence blijft een uitdaging. Daarom is het cruciaal samen met patiënt met behulp van samen beslissen tot een keuze te komen die zowel medisch verantwoord is als aansluit bij de waarden van patiënt en diens steunsysteem.

Onderbouwing

Achtergrond

In patients with peripheral arterial disease and particularly claudication complaints, it is unclear whether endovascular treatment is superior to optimal medication with supervised gait therapy in the long term. Invasive treatments in respect of claudication complaints are effective in the short term, however, complementary value is disappointing in the long term. For critical limb ischaemia (chronic limb-threatening ischaemia; CLTI), re-vascularisation is indicated to prevent major amputation. However, this is a vulnerable group of patients, many of whom are elderly and have extensive co-morbidities. Patients with critical ischaemia therefore have an increased risk of amputation and mortality. It remains a dilemma in many patients whether they can cope with bypass surgery or would benefit more from endovascular treatment.

Conclusies / Summary of Findings

PICO 1: Endovascular treatment with a stent and/or balloon angioplasty or surgical bypass in patients with chronic limb-threatening ischemia

Major amputation (critical)

Very low GRADE

The evidence is very uncertain about the effect of endovascular treatment on major amputation when compared with surgical bypass in patients with chronic limb-threatening ischemia.

Sources: Bradbury (2023 – BASIL-2); Farber (2022 – BEST-CLI).

Reintervention

Moderate GRADE

Endovascular treatment does not likely result in less reinterventions when compared with surgical bypass in patients with chronic limb-threatening ischemia.

Sources: Bradbury (2023 – BASIL-2); Farber (2022 – BEST-CLI).

Mortality (critical)

Very low GRADE

The evidence is very uncertain about the effect of endovascular treatment on mortality when compared with surgical bypass in patients with chronic limb-threatening ischemia.

Sources: Bradbury (2023 – BASIL-2); Bradbury (2005 – BASIL); Farber (2022 – BEST-CLI).

Patency (important)

Primary patency

No GRADE

Due to a lack of useful statistical information, it was not possible to draw a conclusion regarding the predefined outcome primary patency in patients with chronic limb-threatening ischemia.

Sources: Eleissaway (2019).

Secondary patency

No GRADE

Due to a lack of useful statistical information, it was not possible to draw a conclusion regarding the predefined outcome secondary patency in patients with chronic limb-threatening ischemia.

Sources: Eleissaway (2019).

Technical success (important)

Moderate GRADE

Endovascular treatment does likely result in a higher probability in technical success when compared with surgical bypass in patients with chronic limb-threatening ischemia.

Sources: Farber (2022).

Quality of life (important)

Low GRADE

Endovascular treatment may not improve quality of life when compared with surgical bypass in patients with chronic limb-threatening ischemia.

Sources: Bradbury (2023 – BASIL-2).

Wound healing (important)

No GRADE

Since none of the included studies reported information regarding wound healing, it was not possible to draw a GRADE-conclusion regarding wound healing patients with chronic limb-threatening ischemia.

Sources: -

Conclusions

PICO 2: Endovascular treatment with a stent and/or balloon angioplasty or surgical bypass in patients with intermittent claudication

Quality of life (critical)

No GRADE

Since none of the included studies reported information regarding wound healing, it was not possible to draw a GRADE-conclusion regarding quality of life in patients with intermittent claudication.

Sources: -

Patency (critical)

Primary patency

No GRADE

Due to a lack of useful statistical information, it was not possible to draw a conclusion regarding the predefined outcome primary patency in patients with intermittent claudication.

Sources: Bosiers (2020); Enzmann (2019); McQuade (2009).

Secondary patency

No GRADE

Due to a lack of useful statistical information, it was not possible to draw a conclusion regarding the predefined outcome secondary patency in patients with intermittent claudication.

Sources: Bosiers (2020); Enzmann (2019); McQuade (2009).

Clinically driven target lesion revascularization (critical)

No GRADE

Due to a lack of useful statistical information, it was not possible to draw a conclusion regarding the predefined outcome clinically driven target lesion revascularization in patients with intermittent claudication.

Sources: -

Amputation (important)

Very low GRADE

The evidence is very uncertain about the effect of endovascular treatment on amputation when compared with surgical bypass in patients with intermittent claudication.

Sources: Bosiers (2020); Enzmann (2019).

Technical success (important)

Low GRADE

Endovascular treatment may result in little to no difference in technical success when compared with surgical bypass in patients with intermittent claudication.

Sources: Bosiers (2020); Enzmann (2019); McQuade (2009).

Wound healing (important)

No GRADE

Since none of the included studies reported information regarding wound healing, it was not possible to draw a GRADE-conclusion regarding wound healing in patients with intermittent claudication.

Sources: -

Samenvatting literatuur

PICO 1: Endovascular treatment with a stent and/or balloon angioplasty or surgical bypass in patients with chronic limb-threatening ischemia

Systematic review(s)

Randomized controlled trial(s)

The multicenter randomized controlled trial of Bradbury (2023; BASIL-2) investigated the effect of endovascular treatment with a vein bypass in patients with chronic limb threatening ischemia who required infra-popliteal, with or without an additional more proximal infra-inguinal, re-vascularization procedure to restore limb perfusion. In total, 345 patients were enrolled and randomly assigned to either endovascular treatment (N=173) or surgical bypass (N=172). Any endovascular device being used as part of standard of care was permissible. For surgical bypass, any vein deemed suitable by the responsible vascular surgeons could be used. All patients were included in the intention-to-treat analysis. The maximum length of follow-up was 24 months. The reported outcomes in Bradbury (2023; BASIL-2) were mortality, amputation, reintervention, and quality of life.

The randomized controlled trial of Farber (2022; BEST-CLI) investigated the effect of endovascular treatment in comparison with surgical revascularization in patients with chronic limb-threatening ischemia caused by infrainguinal peripheral artery disease. The study included two separate cohorts. Patients with a single segment of great saphenous vein underwent randomization in cohort 1, in which 719 patients received surgical treatment and 716 received endovascular treatment. Cohort 2 consisted of patients without a single segment of great saphenous vein. Of these, 197 patients received surgical treatment and 199 received endovascular treatment. All patients were included in the intention-to-treat analysis. The maximum length of follow-up was 24 months. The reported outcomes in Farber (2022; BEST-CLI) were mortality, reintervention, and amputation.

The randomized controlled trials of Eleissaway (2019) investigated the effect of endovascular treatment with a surgical bypass in patients with trans-atlantic inter-society consensus IIB, C, or D lesions, having a patent popliteal artery. In total, 53 patients were enrolled and randomly assigned to either endovascular treatment (ipsilateral antegrade angioplasty) (N=28) or surgical bypass (N=25). The maximum length of follow-up was twelve months. The reported outcome in Eleissaway (2019) was patency.

The randomized controlled trial of Bradbury (2005; BASIL) investigated the outcome of endovascular treatment with balloon angioplasty in comparison with surgical bypass in patients with severe limb ischemia. In total, 452 patients were enrolled and randomly assigned to either endovascular treatment (N=224) or surgical bypass (N=228). All patients were included in the intention-to-treat analysis. The maximum length of follow-up was 24 months. The reported outcome in Bradbury (2005; BASIL) were mortality, amputation, and quality of life.

PICO 2: Endovascular treatment with a stent and/or balloon angioplasty or surgical bypass in patients with intermittent claudication

Systematic review(s)

Randomized controlled trial(s)

The randomized controlled trial of Bosiers (2020) investigated the effect of endovascular treatment (with a stent) in comparison with prosthetic (Dacron or expanded polytetrafluoroethylene) surgical bypass in patients with patients with femoropopliteal lesions. In total, 220 patients were enrolled and randomly assigned to either endovascular treatment with a stent (N=113) or surgical bypass (N=107). Standard procedures were followed based on the instructions for use for the devices. Intraoperative heparinization (5000 units) was applied in both treatment groups. The only pretreatment allowed prior to placement of the stent was standard balloon angioplasty; no re-entry or atherectomy devices were permitted. The use of pre- and post-dilation was recommended but at the physician’s discretion. Two patients in the endovascular treatment group and three patients in the surgical bypass group were lost to follow-up. The maximum length of follow-up was twelve months. The reported outcome in Bosiers (2020) was patency.

The randomized controlled trial of Enzmann (2019) investigated the effect of endovascular treatment in comparison with surgical bypass in patients with long femoropopliteal lesions. In total, 103 patients were enrolled and randomly assigned to either endovascular treatment with a stent (N=50) or surgical bypass (N=53). In the endovascular group, a contralateral retrograde, ipsilateral antegrade, or retrograde access via the distal popliteal artery, in a prone positioned patient, was used according to surgeon’s preference. In the surgical bypass group, standard femoropopliteal surgical bypass was used with systemic heparinization as well as proximal and distal end-to-side anastomoses. When the common femoral artery (CFA) was stenosed or occluded, endarterectomy was performed as well. The preferred conduit was the greater saphenous vein. No patients were lost to follow-up. The maximum length of follow-up was 24 months. The reported outcomes in Enzmann (2019) were patency and amputation.

The randomized controlled trial of McQuade (2009) compared the efficacy of endovascular treatment with a stent graft in comparison with surgical bypass in patients with superficial femoral artery occlusive diseases. In total, 86 patients were enrolled and randomly assigned to either endovascular treatment (N=40) or surgical bypass (N=46). The maximum length of follow-up was 24 months. The reported outcome in McQuade (2009) was patency.

Results

PICO 1: Endovascular treatment with a stent and/or balloon angioplasty or surgical bypass in patients with chronic limb-threatening ischemia

Major amputation (critical)

Amputations were reported in three studies (Bradbury, 2023 – BASIL-2; Farber, 2022 – BEST-CLI cohort 1; Farber, 2022 – BEST-CLI cohort 2). Bradbury (2023 – BASIL-2) reported major amputations. Farber (2022 – BEST-CLI cohort 1 & 2) reported amputation above the ankle. The results were pooled in a meta-analysis. The pooled number of amputations in the endovascular treatment group was 166/1088 (15.2%), compared to 139/1087 (12.8%) in the surgical bypass group. This resulted in a pooled relative risk ratio (RR) of 1.11 (95% CI 0.80 to 1.55), in favor of surgical bypass treatment (figure 1). This was not considered as a clinically relevant difference.

Figure 1: Forest plot showing the comparison between endovascular treatment to surgical bypass for amputations in patients with chronic limb-threatening ischemia. Pooled risk-ratio, random effects model. Z: p-value of overall effect; df: degrees of freedom; I2; statistical heterogeneity; CI: confidence interval.

Reintervention (critical)

Reinterventions were reported in three studies (Bradbury, 2023 – BASIL-2; Farber, 2022 – BEST-CLI cohort 1; Farber, 2022 – BEST-CLI cohort 2). Bradbury (2023 – BASIL-2) reported reinterventions in general, while Farber (2022 – BEST-CLI cohort 1 & 2) made a distinction between major and minor reinterventions. Bradbury (2023 – BASIL-2) defined reinterventions as a repeat of the same type of procedure (e.g., vein bypass followed by an endovascular procedure). Farber (2022) defined reinterventions as a new bypass, interposition graft revision, thrombectomy, or thrombolysis. The results of the major interventions in Farber (2022 – BEST-CLI) were pooled with the results from Bradbury (2023 – BASIL-2). The minor reinterventions from Farber (2022 – BEST-CLI) were presented separately.

The pooled number of reinterventions in the endovascular treatment group was 251/1088 (23.1%), compared to 103/1087 (9.5%) in the surgical bypass group. This resulted in a pooled relative risk ratio (RR) of 2.40 (95% CI 1.75 to 3.28), in favor of surgical bypass treatment (figure 2). This was considered as a clinically relevant difference.

Figure 2: Forest plot showing the comparison between endovascular treatment to surgical bypass for reinterventions in patients with chronic limb-threatening ischemia. Pooled risk-ratio, random effects model. Z: p-value of overall effect; df: degrees of freedom; I2; statistical heterogeneity; CI: confidence interval.

The number of minor reinterventions in the study of Farber (2022 – BEST-CLI) in the endovascular treatment group was 237/716 (33.1%), compared to 205/718 (28.6%) in the surgical bypass group. This resulted in a relative risk ratio (RR) of 1.16 (95% CI 0.63 to 6.03), in favor of surgical bypass treatment. This was not considered as a clinically relevant difference.

Mortality (critical)

Four studies reported mortality (Bradbury, 2023 – BASIL-2; Bradbury, 2005 – BASIL; Farber, 2022 – BEST-CLI cohort 1; Farber, 2022 – BEST-CLI cohort 2). Bradbury (2023) reported the 30-day mortality rate, while Bradbury (2005) reported the mortality rate during the same hospital stay as the first intervention. Farber (2022 – BEST-CLI cohort 1 & 2) reported deaths from any cause. The results were pooled in a meta-analysis. The pooled mortality rate in the endovascular treatment group was 329/1325 (24.8%), compared to 309/1284 (24.1%) in the surgical bypass group. This resulted in a pooled relative risk ratio (RR) of 0.94 (95% CI 0.70 to 1.27), in favor of endovascular treatment (figure 3). This was not considered as a clinically relevant difference.

Figure 3: Forest plot showing the comparison between endovascular treatment to surgical bypass for mortality in patients with chronic limb-threatening ischemia. Pooled risk-ratio, random effects model. Z: p-value of overall effect; df: degrees of freedom; I2; statistical heterogeneity; CI: confidence interval.

Patency (important)

Primary patency

Primary patency was reported in one study (Eleissaway, 2019). Eleissaway (2019) reported primary patency at twelve months follow-up. Primary patency was defined as an absence of occlusion or significant restenosis (less than 30%) within the treated segment. The results are depicted in table 1.

Table 1. Primary patency rates in patients with claudication intermittens

Author	Primary patency endovascular treatment group (%)	Primary patency surgical bypass group (%)
Eleissaway (2019)	64.5%	72.0%

Secondary patency

Secondary patency was reported in one study (Eleissaway, 2019). Eleissaway (2019) reported secondary patency at twelve months follow-up. Secondary patency was defined as the use of an additional procedure, to regain patency, after reocclusion. The results are depicted in table 2.

Table 2. Secondary patency rates in patients with claudication intermittens

Author	Secondary patency endovascular treatment group (%)	Secondary patency surgical bypass group (%)
Eleissaway (2019)	74.2%	81.6%

Technical success (important)

Technical success was reported in one study (Farber, 2022 – BEST-CLI cohort 1; Farber, 2022 – BEST-CLI cohort 2). Technical success was defined as reestablishment of patency with a residual stenosis of less than 30% for endovascular interventions, or a patent graft with optimal Doppler flow for surgical bypasses.

The number of technical successes in cohort 1 in the endovascular treatment group was 596/704 (84.7%), compared to 651/662 (98.3%) in the surgical bypass group. This resulted in a relative risk (RR) of 1.16 (95% CI 1.12 to 1.20), in favor of surgical bypass. This was not considered as a clinically relevant difference.

Quality of life (important)

Quality of life was reported in one study (Bradbury, 2023 – BASIL-2). Quality of life was quantified with the EQ-5D-5L questionnaire. The EQ-5D is a standardized instrument that scores at five levels of health (mobility, self-care, daily activities, pain/discomfort, and anxiety/depression). From this, a weighted health index can be derived for an individual or population. The patient must indicate how he perceives his health status on a scale of 0 to 100, in which 100 means ‘the best health you can imagine’ and zero means ‘the worst health you can imagine’. The mean (SD) EQ-5D-5L score in the endovascular treatment group (N=85) was 63.2 (21.6) points, compared to 58.5 (22.7) points in the surgical bypass group (N=76). This resulted in a mean difference (MD) of 4.70 (95% CI -2.17 to 11.57), in favor of endovascular treatment. This was not considered as a clinically relevant difference.

Wound healing (important)

None of the included studies reported information regarding wound healing for the comparison of endovascular treatment and surgical bypass in patients with chronic limb-threatening ischemia.

Results

PICO 2: Endovascular treatment with a stent and/or balloon angioplasty or surgical bypass in patients with intermittent claudication

Quality of life (critical)

None of the included studies reported information regarding quality of life for the comparison of endovascular treatment and surgical bypass in patients with intermittent claudication.

Patency (critical)

Primary patency

Primary patency was reported in three studies (Bosiers, 2020; Enzmann, 2019; McQuade, 2009). Bosiers (2020) and Enzmann (2019) reported primary patency at twelve months follow-up, while McQuade (2009) reported primary patency at 24 months follow-up. In Bosiers (2020), patency for the endovascular treatment was defined as no evidence of binary restenosis or occlusion within the target lesion based on a duplex-derived peak systolic velocity ratio less than 2.4 and no clinically-driven target lesion revascularization. For bypass treatment, patency was defined as no evidence of binary restenosis or occlusion at the anastomoses or over the entire length of the bypass graft based on a peak systolic velocity ratio less than 2.4 and no clinically driven reintervention to restore flow in the bypass. Enzmann (2019) defined primary patency as absence of occlusion or flow-limiting stenosis (peak systolic velocity ratio more than 2.5) of the treated segment including one centimeter proximal and distal of the anastomosis. The studies only reported the primary patency rates. The results are depicted in table 3.

Table 3. Primary patency rates in patients with intermittent claudication

Author	Follow-up	Primary patency endovascular treatment group (%)	Primary patency surgical bypass group (%)
Bosiers (2020)	12 months	74.5%	72.5%
Enzmann (2019)	12 months	60.0%	56.0%
McQuade (2009)	24 months	63.0%	64.0%

Secondary patency

Secondary patency was reported in three studies (Bosiers, 2020; Enzmann, 2019; McQuade, 2009). Bosiers (2020) and Enzmann (2019) reported secondary patency at twelve months follow-up, while McQuade (2009) reported secondary patency at 24 months follow-up. In Bosiers (2020), patency for the endovascular treatment was defined as no evidence of binary restenosis or occlusion within the target lesion based on a duplex-derived peak systolic velocity ratio less than 2.4 and no clinically-driven target lesion revascularization. For bypass treatment, patency was defined as no evidence of binary restenosis or occlusion at the anastomoses or over the entire length of the bypass graft based on a peak systolic velocity ratio less than 2.4 and no clinically driven reintervention to restore flow in the bypass. Enzmann (2019) defined secondary patency as a secondary procedure performed for graft of stent occlusion in an afterward patent vessel. The studies only reported the secondary patency rates. The results are depicted in table 4.

Table 4. Secondary patency rates in patients with intermittent claudication

Author	Follow-up	Secondary patency endovascular treatment group (%)	Secondary patency surgical bypass group (%)
Bosiers (2020)	12 months	95.1%	95.9%
Enzmann (2019)	12 months	72.0%	73.0%
McQuade (2009)	24 months	74.0%	76.0%

Clinically driven target lesion revascularization (critical)

Clinically driven target lesion revascularization was reported in two studies (Bosiers, 2020; Enzmann, 2019). Bosiers (2020) reported freedom from target lesion revascularization at twelve months follow-up. Enzmann (2019) reported freedom from target lesion revascularization at 24 months follow-up. The studies only reported the freedom from target lesion revascularization rates. The results are depicted in table 4.

Table 3. Primary patency rates in patients with intermittent claudication

Author	Follow-up	Freedom from target lesion revascularization endovascular treatment group (%)	Freedom from target lesion revascularization surgical bypass group (%)
Bosiers (2020)	12 months	80.9%	76.2%
Enzmann (2019)	24 months	75.0%	67.0%

Amputation (important)

Amputations were reported in two studies (Bosiers, 2020; Enzmann, 2019). Bosiers (2020) reported major amputations. Enzmann (2019) reported minor amputations. The results were pooled in a meta-analysis. The pooled number of amputations in the endovascular treatment group was 6/168 (3.6%), compared to 7/162 (4.3%) in the surgical bypass group. This resulted in a pooled relative risk ratio (RR) of 0.84 (95% CI 0.29 to 2.42), in favor of endovascular treatment (figure 4). This was not considered as a clinically relevant difference.

Figure 4: Forest plot showing the comparison between endovascular treatment to surgical bypass for amputations in patients with intermittent claudication. Pooled risk-ratio, random effects model. Z: p-value of overall effect; df: degrees of freedom; I2; statistical heterogeneity; CI: confidence interval.

Technical success (important)

Technical success was reported in three studies (Bosiers, 2020; Enzmann, 2019; McQuade, 2009). Bosiers (2020) defined technical success for the endovascular treatment as residual restenosis equal or less than 30% by angiography or less than 50% by ultrasound. Bosiers defined technical success for bypass treatment as no graft lesion and a low resistance blood flow pattern in the distal graft and outflow artery, a residual stenosis of less than 50% evidenced on duplex. Enzmann (2019) defined technical success as completion of the procedure and less than 30% residual stenosis. The results were pooled in a meta-analysis. The pooled number of technical successes in the endovascular treatment group was 201/208 (96.6%), compared to 208/824 (25.2%) in the surgical bypass group. This resulted in a pooled relative risk ratio (RR) of 0.44 (95% CI 0.09 to 2.21), in favor of endovascular treatment (figure 5). This was considered as a clinically relevant difference.

Figure 5: Forest plot showing the comparison between endovascular treatment to surgical bypass for technical success in patients with intermittent claudication. Pooled risk-ratio, random effects model. Z: p-value of overall effect; df: degrees of freedom; I2; statistical heterogeneity; CI: confidence interval.

Wound healing (important)

None of the included studies reported information regarding wound healing for the comparison of endovascular treatment and surgical bypass in patients with intermittent claudication.

Level of evidence of the literature

PICO 1: Endovascular treatment with a stent and/or balloon angioplasty or surgical bypass in patients with chronic limb-threatening ischemia

Major amputation (critical)

The level of evidence regarding the outcome major amputation was derived from randomized controlled trials and therefore started high. The level of evidence was downgraded by three levels because of the wide confidence interval crossing both thresholds of clinical relevance (imprecision, -2), and heterogeneity in the study results (inconsistency, -1). The level of evidence was considered as very low.

Reintervention (critical)

The level of evidence regarding the outcome reintervention was derived from randomized controlled trials and therefore started high. The level of evidence was downgraded by one level because of a lack of blinding in the included studies (risk of bias, -1). The level of evidence was considered as moderate.

Mortality (critical)

The level of evidence regarding the outcome mortality was derived from randomized controlled trials and therefore started high. The level of evidence was downgraded by three levels because of a lack of blinding in the included studies (risk of bias, -1) and the wide confidence interval crossing both thresholds of clinical relevance (imprecision, -2). The level of evidence was considered as very low.

Patency (important)

Primary patency

Due to a lack of statistical information, no level of evidence could be determined for the outcome primary patency in patients with chronic limb-threatening ischemia.

Secondary patency

Due to a lack of statistical information, no level of evidence could be determined for the outcome secondary patency in patients with chronic limb-threatening ischemia.

Technical success (important)

The level of evidence regarding the outcome technical success was derived from a randomized controlled trial and therefore started high. The level of evidence was downgraded by one level because of a lack of blinding in the included studies (risk of bias, -1). The level of evidence was considered as moderate.

Quality of life (important)

The level of evidence regarding the outcome quality of life was derived from a randomized controlled trial and therefore started high. The level of evidence was downgraded by one level because of a lack of blinding in the included studies (risk of bias, -1) and the wide confidence interval crossing the upper threshold of clinical relevance (imprecision, -1). The level of evidence was considered as low.

Wound healing (important)

Since none of the included studies reported information regarding wound healing, no level of evidence could be determined for the outcome wound healing in patients with chronic limb-threatening ischemia.

Level of evidence of the literature

PICO 2: Endovascular treatment with a stent and/or balloon angioplasty or surgical bypass in patients with intermittent claudication

Quality of life (critical)

Since none of the included studies reported information regarding quality of life, no level of evidence could be determined for the outcome quality of life in patients with intermittent claudication.

Patency (critical)

Primary patency

Due to a lack of statistical information, no level of evidence could be determined for the outcome primary patency in patients with intermittent claudication.

Secondary patency

Due to a lack of statistical information, no level of evidence could be determined for the outcome secondary patency in patients with intermittent claudication.

Clinically driven target lesion revascularization (critical)

Due to a lack of statistical information, no level of evidence could be determined for the outcome clinically driven target lesion revascularization in patients with intermittent claudication.

Amputation (important)

The level of evidence regarding the outcome amputation was derived from randomized controlled trials and therefore started high. The level of evidence was downgraded by three levels because of heterogeneity between the intervention in the included studies (inconsistency, -1) and the wide confidence interval crossing both thresholds of clinical relevance (imprecision, -2). The level of evidence was considered as very low.

Technical success (important)

The level of evidence regarding the outcome technical success was derived from randomized controlled trials and therefore started high. The level of evidence was downgraded by three levels because of a lack of blinding in the included studies (risk of bias, -1) and heterogeneity in the study results (inconsistency, -1). The level of evidence was considered as low.

Wound healing (important)

Since none of the included studies reported information regarding wound healing, no level of evidence could be determined for the outcome wound healing in patients with intermittent claudication.

Zoeken en selecteren

A systematic review of the literature was performed to answer the following questions: What are the benefits and harms of endovascular treatment with a PTA with or without stenting compared with a surgical bypass in patients with chronic limb-threatening ischemia?

What are the benefits and harms of endovascular treatment with a stent and/or balloon compared with a surgical bypass in patients with intermittent claudication?

PICO 1

P: Patients with chronic limb-threatening ischemia.

I: Endovascular treatment with a stent and/or balloon angioplasty.

C: Surgical bypass.

O: Major amputation, reintervention, mortality, patency, technical success, quality of life, wound healing

PICO 2

P: Patients with intermittent claudication.

I: Endovascular treatment with a stent and/or balloon angioplasty.

C: Surgical bypass.

O: Quality of life, primary patency, clinically driven target lesion revascularization, amputation, technical success, wound healing.

PICO 1: Endovascular treatment with a stent and/or balloon angioplasty versus surgical bypass in patients with chronic limb-threatening ischemia

Relevant outcome measures

The guideline development group considered major amputation, reintervention, and mortality as critical outcomes for decision making and patency, technical success, quality of life, and wound healing as important outcomes for decision making for the comparison of endovascular treatment with a stent and/or balloon angioplasty in patients with chronic limb-threatening ischemia.

As minimal clinically (patient) important differences, the working group used 5% for mortality (risk ratio; RR), 25% for other RR, 10% of the maximum score for continuous outcomes (quality of life scales) and 0.5 for standardized mean differences.

Search and select (Methods)

The databases Medline (via OVID) and Embase (via Embase.com) were searched with relevant search terms until the 14^th of April 2022. However, since the literature search was incomplete, the search strategy was sensitized and expanded to include additional terminology. The detailed search strategy of the primary search and the update of the literature search is depicted under the tab Methods. The systematic literature search eventually resulted in 1326 hits. Studies were selected based on the following criteria: systematic reviews and randomized controlled trials on endovascular treatment of the femoropopliteal tract. Seventeen studies were initially selected based on title and abstract screening. After reading the full text, ten studies were excluded (see the table with reasons for exclusion under the tab Methods) and seven studies, of which four studies were relevant for PICO 1, were included.

Results

Four studies were included in the analysis of the literature for PICO 1. Important study characteristics and results are summarized in the evidence tables. The assessment of the risk of bias is summarized in the risk of bias tables.

PICO 2: Endovascular treatment with a stent and/or balloon angioplasty or surgical bypass in patients with intermittent claudication

Uitgangsvraag

Wat is de waarde van endovasculaire behandeling bij patiënten met claudicatio intermittens?

Search and select

A systematic review of the literature was performed to answer the following questions: What are the benefits and harms of endovascular treatment with a stent and/or balloon compared with a surgical bypass in patients with intermittent claudication?

P: Patients with intermittent claudication.

I: Endovascular treatment with a stent and/or balloon angioplasty.

C: Surgical bypass.

O: Quality of life, primary patency, clinically driven target lesion revascularization, amputation,

technical success, wound healing.

Relevant outcome measures

The guideline development group considered quality of life, primary patency, and clinically driven target lesion revascularization as critical outcomes for decision making and amputation, reintervention, technical success, and wound healing as important outcomes for decision making for the comparison of endovascular treatment with a stent and/or balloon angioplasty in patients with intermittent claudication.

As minimal clinically (patient) important differences, the working group used 25% for RR, 10% of the maximum score for continuous outcomes (quality of life scales) and 0.5 for standardized mean differences.

Search and select (Methods)

The databases Medline (via OVID) and Embase (via Embase.com) were searched with relevant search terms until the 14^th of April 2022. However, since the literature search was incomplete, the search strategy was sensitized and expanded to include additional terminology. The detailed search strategy of the primary search and the update of the literature search is depicted under the tab Methods. The systematic literature search eventually resulted in 1326 hits. Studies were selected based on the following criteria: systematic reviews and randomized controlled trials on endovascular treatment of the femoropopliteal tract. Seventeen studies were initially selected based on title and abstract screening. After reading the full text, ten studies were excluded (see the table with reasons for exclusion under the tab Methods) and seven studies of which three studies were relevant for PICO 2, were included.

Results

Three studies were included in the analysis of the literature for PICO 2. Important study characteristics and results are summarized in the evidence tables. The assessment of the risk of bias is summarized in the risk of bias tables.

Referenties

Adam DJ, Beard JD, Cleveland T, Bell J, Bradbury AW, Forbes JF, Fowkes FG, Gillepsie I, Ruckley CV, Raab G, Storkey H; BASIL trial participants. Bypass versus angioplasty in severe ischaemia of the leg (BASIL): multicentre, randomised controlled trial. Lancet. 2005 Dec 3;366(9501):1925-34. doi: 10.1016/S0140-6736(05)67704-5. PMID: 16325694.
Bosiers M, Setacci C, De Donato G, Torsello G, Silveira PG, Deloose K, Scheinert D, Veroux P, Hendriks J, Maene L, Keirse K, Navarro T, Callaert J, Eckstein HH, Teβarek J, Giaquinta A, Wauters J. ZILVERPASS Study: ZILVER PTX Stent vs Bypass Surgery in Femoropopliteal Lesions. J Endovasc Ther. 2020 Apr;27(2):287-295. doi: 10.1177/1526602820902014. Epub 2020 Jan 30. Erratum in: J Endovasc Ther. 2020 Feb 18;:1526602820908729. PMID: 31997715.
Bradbury AW, Moakes CA, Popplewell M, Meecham L, Bate GR, Kelly L, Chetter I, Diamantopoulos A, Ganeshan A, Hall J, Hobbs S, Houlind K, Jarrett H, Lockyer S, Malmstedt J, Patel JV, Patel S, Rashid ST, Saratzis A, Slinn G, Scott DJA, Zayed H, Deeks JJ; BASIL-2 Investigators. A vein bypass first versus a best endovascular treatment first revascularisation strategy for patients with chronic limb threatening ischaemia who required an infra-popliteal, with or without an additional more proximal infra-inguinal revascularisation procedure to restore limb perfusion (BASIL-2): an open-label, randomised, multicentre, phase 3 trial. Lancet. 2023 May 27;401(10390):1798-1809. doi: 10.1016/S0140-6736(23)00462-2. Epub 2023 Apr 25. PMID: 37116524.
Eleissawy MI, Elbarbary AH, Elwagih MM, Elheniedy MA, Santoso C, Fourneau I. Ipsilateral Antegrade Angioplasty for Flush Superficial Femoral Artery Occlusion versus Open Bypass Surgery. Ann Vasc Surg. 2019 Nov;61:55-64. doi: 10.1016/j.avsg.2019.05.062. Epub 2019 Aug 5. PMID: 31394228.
Enzmann FK, Nierlich P, Aspalter M, Hitzl W, Dabernig W, Hölzenbein T, Ugurluoglu A, Seitelberger R, Linni K. Nitinol Stent Versus Bypass in Long Femoropopliteal Lesions: 2-Year Results of a Randomized Controlled Trial. JACC Cardiovasc Interv. 2019 Dec 23;12(24):2541-2549. doi: 10.1016/j.jcin.2019.09.006. Epub 2019 Nov 27. PMID: 31786218.
Farber A, Menard MT, Conte MS, Kaufman JA, Powell RJ, Choudhry NK, Hamza TH, Assmann SF, Creager MA, Cziraky MJ, Dake MD, Jaff MR, Reid D, Siami FS, Sopko G, White CJ, van Over M, Strong MB, Villarreal MF, McKean M, Azene E, Azarbal A, Barleben A, Chew DK, Clavijo LC, Douville Y, Findeiss L, Garg N, Gasper W, Giles KA, Goodney PP, Hawkins BM, Herman CR, Kalish JA, Koopmann MC, Laskowski IA, Mena-Hurtado C, Motaganahalli R, Rowe VL, Schanzer A, Schneider PA, Siracuse JJ, Venermo M, Rosenfield K; BEST-CLI Investigators. Surgery or Endovascular Therapy for Chronic Limb-Threatening Ischemia. N Engl J Med. 2022 Dec 22;387(25):2305-2316. doi: 10.1056/NEJMoa2207899. Epub 2022 Nov 7. PMID: 36342173.
McQuade K, Gable D, Hohman S, Pearl G, Theune B. Randomized comparison of ePTFE/nitinol self-expanding stent graft vs prosthetic femoral-popliteal bypass in the treatment of superficial femoral artery occlusive disease. J Vasc Surg. 2009 Jan;49(1):109-15, 116.e1-9; discussion 116. doi: 10.1016/j.jvs.2008.08.041. Epub 2008 Nov 22. PMID: 19028055.

Evidence tabellen

Study reference

Study characteristics

Patient characteristics ²

Intervention (I)

Comparison / control (C) ³

Follow-up

Outcome measures and effect size ⁴

Comments

Bradbury (2023) (BASIL-2)

Type of study:

RCT.

Setting and country:

41 vascular surgery units in the UK

Funding and conflicts of interest:

The funder had no role in study design, data collection, data analysis, data interpretation, writing of the report, or decision to submit the results for publication.

All other authors declare no competing interests.

Inclusion criteria:

Life expectancy of more than 6 months, and judged by a minimum of two consultants (at least one of whom could undertake infra-popliteal vein bypass and one of whom could undertake infra-popliteal endovascular interventions in their clinical practice) to require and be suitable for both infra-popliteal vein bypass and infra-popliteal endovascular intervention.

Exclusion criteria:

Ischaemic pain or tissue loss considered not to be primarily due to atherosclerotic peripheral artery disease.

N total at baseline:

Intervention: N = 173

Control: N = 172

Important prognostic factors²:

age:

I: 72.5 (62.7 to 79.7)

C: 72.4 (64.3 to 78.7)

Sex:

I:141/173 (82%) M

C: 139/172 (81%) M

Groups comparable at baseline?

Yes.

Describe intervention (treatment/procedure/test):

Best endovascular treatment.

Regarding best endovascular treatment, any device being used as part of standard of care in that country was permissible. Drug coated balloons, bare metal stents, and drug eluting stents could be used at the operator’s discretion. Atherectomy devices were permitted but not used. In this pragmatic trial, all additional management strategies, including additional procedures, were at the responsible clinicians’ discretion in the patient’s best interests.

Describe control (treatment/procedure/test):

Vein bypass.

For vein bypass, any vein deemed suitable by the responsible vascular surgeons could be used. If at operation it was discovered that the vein could not be used, then composite or prosthetic grafts could be inserted at the surgeon’s discretion in the patient’s best interests.

Length of follow-up:

Maximum of 24 months.

Loss-to-follow-up:

1 month

I: n=4

C: n=9

6 months

I: n=3

C: n=4

12 months

I: n=2

C: n=3

All participants were analyzed in the intention-to-treat analysis.

No amputation-free survival

I: 92/173 (53%)

C: 108 (63%)

Death from any cause

I: 77/173 (45%)

C: 91/172 (53%)

30-day mortality

I: 5/173 (3%)

C: 10/172 (6%)

Major amputation

I: 32/173 (18%)

C: 35/172 (20%)

Major adverse limb event

I: 77/173 (45%)

C: 71/172 (41%)

Major adverse cardiac event

I: 73/173 (42%)

C: 68/172 (40%)

Reintervention

I: 33/173 (19%)

C: 9/172 (5%)

Quality of life (EQ5D5L health state score) 24 months

I: 63.2 (21.6) (n=85)

C: 58.5 (22.7) (n=76)

Author’s conclusion:

In the BASIL-2 trial, a best endovascular treatment first revascularisation strategy was associated with a better amputation-free survival, which was largely driven by fewer deaths in the best endovascular treatment group. These data suggest that more patients with chronic limb-threatening ischaemia who required an infra-popliteal, with or without an additional more proximal infra-inguinal, revascularisation procedure to restore limb perfusion should be considered for a best endovascular treatment first revascularisation strategy.

Farber (2022) (BEST-CLI)

Type of study:

RCT.

Setting and country:

150 sites in the United States, Canada, Finland, Italy, and New Zealand.

Funding and conflicts of interest:

Inclusion criteria:

Male or female, age 35 years or older.
Atherosclerotic, infrainguinal PAD (occlusive disease of the arteries below the inguinal ligament caused by atherosclerosis).
CLI, defined as arterial insufficiency with gangrene, non-healing ischemic ulcer, or rest pain consistent with Rutherford Categories 4-6.
Candidate for either open or endovascular infrainguinal revascularization as judged by the treating investigators (see MOO for guidelines on decision-making).
Adequate aortoiliac inflow.*
Adequate popliteal, tibial or pedal revascularization target defined as an infrainguinal arterial segment distal to the area of stenosis/occlusion which can support a distal anastomosis of a surgical bypass.
Willingness to comply with protocol, attend follow-up appointments, complete all study assessments, and provide written informed consent.

Exclusion criteria:

Disease limited to the Femoropopliteal segment with TASC II A pattern.
Presence of a femoral, popliteal or tibial aneurysm in the index limb.
Life expectancy of less than 2 years
Deemed excessive risk for surgical bypass (defined as excessive operative risk by preprocedural cardiac risk assessment according to established AHA/ACCF criteria).
Planned above ankle amputation on ipsilateral limb within 4 weeks of index procedure.
Renal dysfunction (defined as MDRD eGFR ≤ 30 mL/min/1.73 m2 at the time of screening).
Current dialysis
History of renal transplantation.
Presence of a documented hypercoagulable state (defined as a known blood disorder associated with venous or arterial thrombosis).
Non-atherosclerotic occlusive disease (e.g. embolic disease, trauma, vasculitis, Buerger’s disease) or acute limb-threatening ischemia (defined as tissue loss or ischemic rest pain of less than 14 days duration).
Any prior infrainguinal stenting or stent grafting (with or without atherectomy and/or balloon angioplasty) of the ipsilateral superficial femoral artery and/or above knee popliteal artery.
Any prior percutaneous or surgical intervention involving arteries below the knee joint.
Any of the following procedures performed within 6 months prior to screening:
- Percutaneous balloon angioplasty or atherectomy of the superficial femoral artery and/or above knee popliteal artery;
- Common, superficial, or deep femoral endarterectomy;
- Femoral to above knee bypass with either venous or prosthetic conduit;
- Open surgical inflow procedure (aortofemoral, axillofemoral, iliofemoral, or femorofemoral bypass) involving the index leg
Current immune-suppressive medication, chemotherapy or radiation therapy.
Absolute contraindication to iodinated contrast due to prior near-fatal anaphylactoid reaction (laryngospasm, bronchospasm, cardiorespiratory collapse, or equivalent) and which would preclude patient participation in angiographic procedures.
Known allergy to stainless steel or nitinol.
Pregnancy or lactation.
Administration of an investigational drug for peripheral arterial disease within 30 days of randomization.
Participation in a clinical trial (except observational studies) within the previous 30 days.

N total at baseline:

Intervention: N = 716

Control: N = 718

Important prognostic factors²:

age ± SD:

I: 67.0 (10.0)

C: 66.9 (9.8)

Sex:

I: 207/716 (28.9%) F

C: 201/718 (28.0%) F

Groups comparable at baseline?

Yes.

Describe intervention (treatment/procedure/test):

Endovascular treatment within 30 days

Describe control (treatment/procedure/test):

Surgical treatment within 30 days

Length of follow-up:

24 months.

Loss-to-follow-up:

I: n=44 (14.3%)

C: n=58 (14.0%)

Death from any cause

I: 269/716 (37.6%)

C: 237/718 (33.0%)

Myocardial infarction

I: 85/716 (11.9%)

C: 75/718 (10.4%)

Above-ankle amputation

I: 106/716 (14.8%)

C: 74/718 (10.3%)

Major reintervention

I: 167/716 (23.3%)

C: 66/718 (9.2%)

Minor reintervention

I: 237/716 (33.1%)

C: 205/718 (28.6%)

Length of hospitalization after index procedure

I: 5.9 (7.3) days.

C: 7.5 (6.2) days.

Technical success

I: 596/704 (84.7%)

C: 651/662 (98.3%)

Author’s conclusion:

Among patients with CLTI who had an adequate great saphenous vein for surgical revascularization (cohort 1), the incidence of a major adverse limb event or death was significantly lower in the surgical group than in the endovascular group. Among the patients who lacked an adequate saphenous vein conduit (cohort 2), the outcomes in the two groups were similar.

Bosiers (2020)

Type of study:

RCT

Setting and country:

clinical sites in Belgium (n=5), Germany (n=4), Italy (n=2),

and Brazil (n=2).

Funding and conflicts of interest:

The author(s) received no financial support for the research,

authorship, and/or publication of this article.

The author(s) declared the following potential conflicts of interest

with respect to the research, authorship, and/or publication of this

article: Pierre Galvagni Silveira received research, clinical trial, or

drug study funds from Cook Medical. Giovanni Torsello received

research grants from Cook Medical. Dr Koen Deloose is a clinical

trial investigator, consultant, and lecturer for Cook Medical. Dierk

Scheinert is a consultant for Cook Medical. Tulio Navarro received

research grants from Cook Medical.

Inclusion criteria:

Inclusion criteria: General

Patient presenting with lifestyle-limiting claudication, rest pain or minor tissue loss (Rutherford category 2 to 5)
Patient is willing to comply with specified follow-up evaluations at the specified times
Patient is >18 years old
Patient understands the nature of the procedure and provides written informed consent prior to enrollment in the study
Patient has a projected life expectancy of at least 24 months
Noninvasive lower extremity arterial studies (resting or exercise) demonstrate ankle-brachial index ≤0.8
Patient is eligible for treatment with the ZILVER PTX paclitaxel-eluting stent (Cook) or with surgical above-the-knee
bypass placement
Male, infertile female, or female of childbearing potential practicing an acceptable method of birth control with a negative pregnancy test within 7 days prior to study procedure

Inclusion criteria: Angiographic

Stenotic or occlusive de novo lesion located in the femoropopliteal arteries, suitable for endovascular therapy and for bypass surgery
Total target lesion length is at least 15 cm
Minimum of 1.0 cm of healthy vessel (non-stenotic) both proximal and distal to the treatment area
P2 and P3 are patent and there is angiographic evidence of at least 1 vessel runoff to the foot that does not require intervention (<50% stenotic)
Target vessel diameter visually estimated to be >4 mm and <9 mm at the proximal and distal treatment segments within the SFA

Exclusion criteria:

Untreated flow-limiting aortoiliac stenotic disease
Any previous surgery and endovascular procedure in the target vessel
Severe ipsilateral common/deep femoral disease requiring surgical reintervention
Perioperative unsuccessful ipsilateral percutaneous vascular procedure to treat inflow disease just prior to enrollment
Femoral or popliteal aneurysm located at the target vessel
Nonatherosclerotic disease resulting in occlusion (eg, embolism, Buerger’s disease, vasculitis)
No patent tibial arteries (>50% stenosis)
Prior ipsilateral femoral artery bypass
Severe medical comorbidities (untreated CAD/CHF, severe COPD, metastatic malignancy, dementia, etc) or other medical condition that would preclude compliance with the study protocol or 2-year life expectancy
Serum creatinine >2.5 mg/dL within 45 days prior to study procedure unless the subject is currently on dialysis
Major amputation (above the transmetatarsal) in the study or nonstudy limb
Any previously known coagulation disorder, including hypercoagulability
Contraindication to anticoagulation or antiplatelet therapy
Known allergies to stent components (nickel-titanium, paclitaxel, etc) or bypass graft components (Dacron, ePTFE, etc)
Known allergy to contrast media that cannot be adequately premedicated prior to the study procedure
Currently participating in another clinical research trial
Angiographic evidence of intra-arterial thrombus or atheroembolism from inflow treatment
Any planned surgical intervention/procedure within 30 days of the study procedure
Target lesion access in the ZILVER PTX stent arm not performed by transfemoral approach

N total at baseline:

Intervention: N = 113

Control: N = 107

Important prognostic factors²:

age ± SD:

I: 69.6 (10.8)

C: 67.6 (10.1)

Sex:

I: 78/113 (69%) M

C: 81/107 (72.3%) M

Groups comparable at baseline?

Yes.

Describe intervention (treatment/procedure/test):

Endovascular treatment with the ZILVER PTX stent.

Describe control (treatment/procedure/test):

Bypass surgery.

Length of follow-up:

60 months maximum.

Loss-to-follow-up:

None.

Technical success

I: 113/113 (100%)

C: 107/107 (100%)

Length of hospital stay

I: 2.5 (3.5) days

C: 8.1 (6.0) days

Complications (30 days)

I: 5/113 (4.3%

C: 12/107 (11.2%)

Primary patency (12 months)

I: (74.5%)

C: (72.5%)

Secondary patency (12 months)

I: (95.1%)

C: (95.9%)

Target lesion revascularization (12 months)

I: (80.9%)

C: (76.2%)

Freedom of major amputation (12 months)

I: (98.0%)

C: (98.1%)

Major amputations (12 months)

I: 2/113 (1.8%)

C: 2/107 (1.9%)

Survival rate (12 months)

I: (94.5%)

C: (96.1%)

Author’s conclusion:

With noninferior patency results, a lower complication rate, and shorter procedures and hospital stays, paclitaxel-eluting stenting might become a recommended treatment for long TASC C and D femoropopliteal lesions.

Eleissaway (2019)

Type of study:

RCT.

Setting and country:

the Vascular Surgery Department of Tanta

University and Leuven University

Funding and conflicts of interest:

There are no conflicts of interest related

to this article.

Inclusion criteria:

patients having the angiographic criteria of flush SFA occlusion lesions, and an outflow artery (at least the below-knee popliteal artery).
lifestylelimiting IC or CLI (Fontaine stages IIb, III, and IV).

Exclusion criteria:

Patients having a potential etiology for lower limb ischemia of acute thromboembolism, trauma, or autoimmune disorders.
Patients having associated CFA lesions or having a CFA bifurcation level higher than the upper margin of the head of femur.
contraindication to endovascular intervention, such as allergy to contrast

N total at baseline:

Intervention: N = 25

Control: N = 25

Important prognostic factors²:

age ± SD:

I: 72 (12.1)

C: 72 (7.5)

Sex:

Not reported.

Groups comparable at baseline?

Yes.

Describe intervention (treatment/procedure/test):

Endovascular treatment (Ipsilateral antegrade angioplasty)

Describe control (treatment/procedure/test):

Bypass surgery.

Length of follow-up:

12 months.

Loss-to-follow-up:

N = 3 intervention group.

Length of hospital stay

I: 1.84 (0.19) days.

C: 6.24 (0.37) days.

Restenosis

I: 3/25 (12%)

C: 2/25 (8%)

Complications

I: 4/25 (16%)

C: 12/25 (48%)

Myocardial infarction

I: 1/25 (4%)

C: 2/25 (8%)

Primary patency

I: (64.5%)

C: (72.0%)

Secondary patency

I: (74.2%)

C: (81.6%)

Author’s conclusion:

Technical success, patency, and limb salvage of endovascular approach were comparable to surgical bypass. The endovascular approach had the advantages of reduced local complications and hospitalization.

Enzmann (2019)

Type of study:

RCT.

Setting and country:

No information.

Funding and conflicts of interest:

No information.

Inclusion criteria:

adult patient;
30 years of age;
informed consent;
severe intermittent claudication (<200 m of walking distance) or critical limb threatening ischemia, including rest pain and ischemic lesions (Rutherford categories 3 to 6);
femoropopliteal TASC II C or D lesions and no untreated inflow lesions in the ipsilateral iliac arteries;
at least 1 patent tibial artery; or symptoms for more than 2 months.

Exclusion criteria:

acute ischemia;
any form of vasculitis, or embolic or traumatic femoropopliteal occlusions; previous ipsilateral bypass surgery; use of a prosthetic conduit;
chronic kidney disease without requiring dialysis
(glomerular filtration rate <45 ml/min/1.73 m2);
patients that are too frail for VBP (American Society of Anesthesiologists [ASA] classification >3);
pregnancy.

N total at baseline:

Intervention: N = 50 (55 lesions)

Control: N = 53 (55 lesions)

Important prognostic factors²:

age ± SD:

I: 69.5 (7.9)

C: 68.3 (8.7)

Sex:

I: 35/50 (70%)

C: 41/53 (77%)

Groups comparable at baseline?

Yes.

Describe intervention (treatment/procedure/test):

Nitinol stents.

Describe control (treatment/procedure/test):

Bypass surgery.

Length of follow-up:

12 months.

Loss-to-follow-up:

None.

Technical success

I: 48/55 (87.3%)

C: 55/55 (100%)

Primary patency

I: (60%)

C: (56%)

Secondary patency

I: (72%)

C: (73%)

Target lesions revascularization

I: 14/55 (25.5%)

C: 14/55 (25.5%)

Revascularization

I: 28/55 (50.9%)

C: 35/55 (63.6%)

Survival (2 years)

I: (90%)

C: (95%)

Overall complications

I: 21/55 (38.2%)

C: 25/55 (45.5%)

Minor amputation

I: 4/55 (7.2%)

C: 5/55 (9.1%)

Author’s conclusion:

There were no significant differences regarding patency rates, limb salvage, survival, or complications.

after 2 years. Technical success and clinical improvement in the bypass group were significantly better, but the promising results of the stent group suggest that an endovascular-first strategy for femoropopliteal lesions up to 30 cm may be reasonable. Mid- as well as long-term results need to be awaited.

McQuade (2009)

Type of study:

RCT

Setting and country:

a single institution.

Funding and conflicts of interest:

Competition of interest: Dr Gable received funding/grants for support of this

study from W.L. Gore & Associates, Flagstaff, Ariz. Dr Gable received fees

from W.L. Gore & Associates for speaking at organized educational events

Inclusion criteria:

patients that had atherosclerotic stenotic or occlusive lesions of the superficial femoral artery with no significant aorto-iliac disease.
The infrapopliteal segment had to be patent with at least single vessel run-off to the ankle.
Patients had to be acceptable surgical candidates in the event they were randomized to the surgical arm.

Exclusion criteria:

No information.

N total at baseline:

Intervention: N = 40

Control: N = 46

Important prognostic factors²:

age ± SD:

I: 72 (9.9)

C: 67 (10.7)

Sex:

No information.

Groups comparable at baseline?

Yes.

Describe intervention (treatment/procedure/test):

Stent graft.

Describe control (treatment/procedure/test):

Surgical bypass.

Length of follow-up:

24 months maximum.

Loss-to-follow-up:

I: N = 4

C: N = 5

Technical success

I: 40/40 (100%)

C: 46/46 (100%)

Complications

I: 4/40 (10.0%)*

C: 3/46 (6.5%)**

*SFA dissection (n=1), transient mild leg edema (n=1), transient thigh pain in the treated limb (n=1), small groin hematoma (n=1).

**groin lymphocele (n=2), small superficial groin wound dehiscence (n=1).

Length of hospital stay

I: 0.9 (0.8) days.

C: 3.1 (1.8) days.

Primary patency (24 months)

I: 63%

C: 64%

Secondary patency (24 months)

I: 74%

C: 76%

Author’s conclusion:

Management of superficial femoral artery occlusive disease with percutaneous stent-grafts exhibits similar primary

patency at 24-month follow-up when compared with conventional femoral-popliteal artery bypass grafting with synthetic conduit.

This treatment method may offer an alternative to treatment of the superficial femoral artery segment for revascularization when

prosthetic bypass is being considered or when autologous conduit is unavailable.

Bradbury (2005)

Type of study:

RCT

Setting and country:

27 UK hospitals

Funding and conflicts of interest:

The sponsor of the study had no role in study design,

data collection, data analysis, data interpretation, or

writing of the report. The corresponding author had full access to all the data in the study and had final responsibility for decision to submit for publication.

The members of the writing committee declare that they have no

conflict of interest.

Inclusion criteria:

all patients who had presented to them with severe limb ischaemia, defined as rest pain or tissue loss (ulcer or gangrene) of presumed arterial aetiology for more than 2 weeks, and who on diagnostic imaging had a pattern of disease which, in their joint opinions, could equally well be treated by either infra-inguinal bypass surgery or balloon angioplasty.

Exclusion criteria:

No information.

N total at baseline:

Intervention: N = 224

Control: N = 228

Important prognostic factors²:

Age

See original publication.

Sex:

No information.

Groups comparable at baseline?

Yes

Describe intervention (treatment/procedure/test):

Balloon angioplasty.

Describe control (treatment/procedure/test):

Bypass surgery

Length of follow-up:

2 years.

Loss-to-follow-up:

N = 7 after randomisation

N = 3 during the first year of follow-up.

Mortality during same hospital stay as first intervention

I: 7/237

C: 11/197

Mortality following discharge from hospital after first intervention

I: 0/230

C: 0/186

Myocardial infarction during same hospital stay as first intervention

I: 6/237

C: 13/197

Myocardial infarction following discharge from hospital after first intervention

I: 1/230

C: 2/186

Author’s conclusion:

Risk of bias tabel

Study reference

(first author, publication year)

Was the allocation sequence adequately generated?

Definitely yes

Probably yes

Probably no

Definitely no

Was the allocation adequately concealed?

Definitely yes

Probably yes

Probably no

Definitely no

Blinding: Was knowledge of the allocated

interventions adequately prevented?

Were patients/healthcare providers/data collectors/assessors/data analysts blinded?

Definitely yes

Probably yes

Probably no

Definitely no

Was loss to follow-up (missing outcome data) infrequent?

Definitely yes

Probably yes

Probably no

Definitely no

Are reports of the study free of selective outcome reporting?

Definitely yes

Probably yes

Probably no

Definitely no

Was the study apparently free of other problems that could put it at a risk of bias?

Definitely yes

Probably yes

Probably no

Definitely no

Overall risk of bias

If applicable/necessary, per outcome measure

LOW

Some concerns

HIGH

Bradbury (2023) (BASIL-2)

Definitely yes

Reason: Participants were randomly assigned (1:1) to receive

either vein bypass (vein bypass group) or best

endovascular treatment (best endovascular treatment

group) as their first revascularisation procedure through

a secure online randomisation system.

No information.

Reason: -

Definitely no.

Reason: BASIL-2 was an open-label study; participants, study

staff, and investigators were not masked to treatment

allocation.

Probably no.

Reason: Lost to follow-up almost equally distributed over both groups and all patients were included in the intention-to-treat analysis.

Probably yes.

Reason: All predefined outcomes were reported.

Probably no.

Reason: No other bias reported.

Some concerns (no blinding and unclear allocation of concealment).

Farber (2022) (BEST-CLI)

Definitely yes.

Reason: Patients were enrolled into one of two paralleltrial cohorts according to prerandomization duplex ultrasonography of the right and left great

saphenous veins.

No information.

Reason: -

Definitely no.

Reason: Open-label study.

Probably no.

Reason: Lost to follow-up almost equally distributed over both groups and all patients were included in the intention-to-treat analysis.

Probably yes.

Reason: All predefined outcomes were reported.

Probably yes.

Reason: Selection and operator bias as a consequence of its pragmatic design and implementation. Eligibility was determined locally and varied according to the site and the individual investigator; patients who underwent randomization were those in whom the enrolling team believed there was equipoise between endovascular intervention and bypass surgery.

Some concerns (no blinding, unclear allocation of concealment and probability of selection bias).

Bosiers (2020)

Definitely yes.

Reason: Using a computer-generated list for each site, permuted

block randomization was applied with block sizes of 8 patients assigned in a 1:1 fashion to either endovascular

treatment with the ZILVER PTX stent or bypass surgery

with a synthetic graft.

Definitely yes.

Reason: Each site received closed envelopes

that were opened only after the patient signed the informed

consent. Once a treatment was assigned, crossover was not

permitted.

No information.

Reason: -

Probably no.

Reason: Lost to follow-up almost equally distributed over both groups.

Probably yes.

Reason: All predefined outcomes were reported.

Probably no.

Reason: No other bias reported.

Some concerns (unclear blinding).

Eleissaway (2019)

Definitely yes.

Reason: patients were prospectively randomized to either endovascular therapy (n ¼ 28 patients) or surgical bypass.

Probably yes.

Reason: Randomization

was accomplished using the opaque closed

envelopes system with a ratio of 1:1.

No information.

Reason: -

Probably no.

Reason: Lost to follow-up almost equally distributed over both groups.

Probably yes.

Reason: All predefined outcomes were reported.

Probably no.

Reason: No other bias reported.

Some concerns (no blinding and unclear allocation of concealment).

Enzmann (2019)

Definitely yes.

Reason: The

design of the study is a randomized, controlled,

monocentric, sample size planned, group-sequential

clinical trial

Definitely yes.

Reason: Patients were allocated to the stent or bypass

group by using stratified randomization (TASC II category and Rutherford category were used as

stratification variables).

No information.

Reason: -

Definitely no.

Reason: No

patient was lost to follow-up with a median follow-up

of 23 (interquartile range: 14.1 to 27.6) months in the

stent group and 21 (interquartile range: 15.7 to 26.0)

months in the bypass group, respectively.

Probably yes.

Reason: All predefined outcomes were reported.

Probably no.

Reason: No other bias reported.

Some concerns (unclear blinding).

McQuade (2009)

Definitely yes.

Reason: the study is a prospective, randomized

Trial. Enrolled patients were prospectively randomized by

limb prior to intervention into one of two treatment

groups: percutaneous endovascular treatment with the

stent-graft or open surgical femoral to above-knee popliteal

artery bypass with synthetic graft.

No information.

Reason: -

No information.

Reason: -

Probably no.

Reason: Lost to follow-up almost equally distributed over both groups.

Probably yes.

Reason: All predefined outcomes were reported.

Probably no.

Reason: No other bias reported.

Some concerns (unclear allocation of concealment and unclear blinding).

Bradbury (2005)

Definitely yes.

Reason: The trial manager, independent of participating centres,

randomly assigned patients to receive either surgery first

or angioplasty first using a one-to-one ratio in randomly

sized permutated blocks.

Probably yes.

Reason: The randomisation sequences

were generated by a computerised random-number

generator in the University of Edinburgh Medical

Statistics Unit (Edinburgh, UK) and supplied to the

coordinating centre in identical, sealed envelopes.

No information.

Reason: -

Probably no.

Reason: Lost to follow-up almost equally distributed over both groups.

Probably yes.

Reason: All predefined outcomes were reported.

Probably no.

Reason: No other bias reported.

Some concerns (unclear blinding).

Exclusie tabel

Author and year	Reason for exclusion
Bradbury (2010a)	Wrong outcomes.
Bradbury (2010b)	Wrong outcomes.
Bradbury (2010c)	Wrong study design.
Forbes (2010)	Wrong outcomes
Kedora (2007)	Duplicate.
Klaphake (2020)	Does not match the PICO of this guideline (wrong comparison of interventions).
Malas (2014)	Wrong study design.
McQuade (2010)	Wrong outcomes.
Siracuse (2023)	Duplicate.
Wolf (1993)	Does not match the PICO of this guideline (wrong comparison of interventions).

Verantwoording

Autorisatiedatum en geldigheid

Laatst beoordeeld : 01-04-2025

Laatst geautoriseerd : 01-04-2025

Geplande herbeoordeling : 01-04-2028

Initiatief en autorisatie

Initiatief:

Nederlandse Vereniging voor Heelkunde

Geautoriseerd door:

Koninklijk Nederlands Genootschap voor Fysiotherapie
Nederlands Huisartsen Genootschap
Nederlandse Internisten Vereniging
Nederlandse Vereniging voor Heelkunde
Nederlandse Vereniging voor Klinische Geriatrie
Verpleegkundigen en Verzorgenden Nederland
Patiëntenfederatie Nederland
Vereniging van Oefentherapeuten Cesar en Mensendieck
Harteraad

Algemene gegevens

De ontwikkeling/herziening van deze richtlijnmodule werd ondersteund door het Kennisinstituut van de Federatie Medisch Specialisten (www.demedischspecialist.nl/kennisinstituut) en werd gefinancierd uit de Kwaliteitsgelden Medisch Specialisten (SKMS).

De financier heeft geen enkele invloed gehad op de inhoud van de richtlijnmodule.

Samenstelling werkgroep

Voor het ontwikkelen van de richtlijnmodule is in 2021 een multidisciplinaire werkgroep ingesteld, bestaande uit vertegenwoordigers van alle relevante specialismen (zie hiervoor de Samenstelling van de werkgroep) die betrokken zijn bij de zorg rondom patiënten met (chronisch) perifeer arterieel vaatlijden van de onderste extremiteit(en).

Werkgroep

Dr. B. (Bram) Fioole (voorzitter), Nederlandse Vereniging voor Heelkunde
Dr. C. (Çagdas) Ünlü, Nederlandse Vereniging voor Heelkunde
Drs. J.L. (Jorg) de Bruin, Nederlandse Vereniging voor Heelkunde
Prof. dr. B.M.E. (Barend) Mees, Nederlandse Vereniging voor Heelkunde
Drs. D.A.F. (Daniel) van den Heuvel, Nederlandse Vereniging voor Radiologie
Dr. S.W. (Sanne) de Boer, Nederlandse Vereniging voor Radiologie
Dr. R. (Rinske) Loeffen), Nederlandse Internisten Vereniging
Dr. M.E.L. (Marie-Louise) Bartelink, Nederlands Huisartsen Genootschap
E. (Emilien) Wegerif, Nederlandse Vereniging voor Heelkunde
J. (Jenny) Zwiggelaar, Koninklijk Nederlands Genootschap voor Fysiotherapie / Vereniging van Oefentherapeuten Cesar en Mensendieck
G. (Gilaine) Kleian, Harteraad
P.A.H. (Patricia) van Mierlo – van den Broek, MANP, Verpleegkundigen & Verzorgenden Nederland / VS Vaatchirurgie Netwerk

Met ondersteuning van:

Dr. W. (Wouter) Harmsen, senior adviseur, Kennisinstituut van de Federatie Medisch Specialisten (tot 2023)
Dr. R. (Romy) Zwarts - van de Putte, adviseur, Kennisinstituut van de Federatie Medisch Specialisten (tot 2023)
Dr. M.S. (Matthijs) Ruiter, senior adviseur, Kennisinstituut van de Federatie Medisch Specialisten (vanaf 2023)
M. (Mitchel) Griekspoor, MSc, adviseur, Kennisinstituut van de Federatie Medisch Specialisten (vanaf 2023)

Belangenverklaringen

De Code ter voorkoming van oneigenlijke beïnvloeding door belangenverstrengeling is gevolgd. Alle werkgroepleden hebben schriftelijk verklaard of zij in de laatste drie jaar directe financiële belangen (betrekking bij een commercieel bedrijf, persoonlijke financiële belangen, onderzoeksfinanciering) of indirecte belangen (persoonlijke relaties, reputatiemanagement) hebben gehad. Gedurende de ontwikkeling of herziening van een module worden wijzigingen in belangen aan de voorzitter doorgegeven. De belangenverklaring wordt opnieuw bevestigd tijdens de commentaarfase.

Een overzicht van de belangen van werkgroepleden en het oordeel over het omgaan met eventuele belangen vindt u in onderstaande tabel. De ondertekende belangenverklaringen zijn op te vragen bij het secretariaat van het Kennisinstituut van de Federatie Medisch Specialisten.

Werkgroeplid	Hoofdfunctie	Project Tekstveld	Nevenwerkzaamheden	Persoonlijke Financiële belangen	Persoonlijke relaties	Extern gefinancierd onderzoek	Intell. Belangen en reputatie	Overige belangen	Ondernomen actie
Bram Fioole (vz.)	Vaatchirurg	Richtlijn Perifeer arterieel vaatlijden	Opleider vaatchirurgie en algemene heelkunde Maasstadziekenhuis, onbetaald Secretaris Stichting DEAll (stichting ter bevordering van wetenschappelijk onderzoek op het gebied van de vaatchirurgie en interventieradiologie), onbetaald.	Geen.	Geen.	Stichting DEAll/FOREST trial/projectleider-> ja Getinge/DISCOVER trial/projectleider-> ja Cook/Zephyr registry/ projectleider -> ja	Geen.	Geen.	Geen restricties voor deelname aan de richtlijn.
Marie-Louise Bartelink	* 80% huisartsdocent en -onderzoeker, associate professor * 20% huisartsdocent	Richtlijn Perifeer arterieel vaatlijden	Geen.	Geen.	Geen.	ZonMw - EBM-leren in de huisartspraktijk, kwalittatieve studies - Projectleider	Geen.	Geen.	Geen restricties voor deelname aan de richtlijn.
Patricia van Mierlo – van den Broek	Verpleegkundig Specialist in het specialisme Algemene Gezondheidszorg werkzaam bij de afdeling Vaatchirurgie.	Richtlijn Perifeer arterieel vaatlijden	Als vrijwilliger werkzaam (onbetaald) als collectant voor een aantal goede doelen (KWF en dierenbescherming)	Geen.	Geen.	Betrokken bij de "FOREST"-trial (randomized comparison of FemORal drug-Eluting balloons and Stents), een gerandomiseerd prospectief multicenter onderzoek waarbij de langere termijn resultaten van drug-eluting ballonnen en stents in het AFS traject onderzocht wordt (NL57055.101.16). Deze trial wordt gesponsord door de stichting DEAII (Dutch Endovascular Alliance).	Geen.	Geen.	Geen restricties voor deelname aan de richtlijn.
Emilien Wegerif	Arts onderzoeker	Richtlijn Perifeer arterieel vaatlijden	Eigenaresse Caro-Jo Amsterdam, eenmanszaak betaald Caro-Jo Amsterdam is een Chaar sierraden merk	Ik heb geen financiële belangen bij de uitkomsten van de publicaties	Geen.	Geen.	Geen.	Geen.	Geen restricties voor deelname aan de richtlijn.
Jenny Zwiggelaar	Fysiotherapeut, hart-vaat-long gespecialiseerd Projectmedewerker Chronisch ZorgNet Beide functies in loondienst	Richtlijn Perifeer arterieel vaatlijden	Geen.	Geen, enkel de bekende werkrelaties.	Geen.	Geen.	Geen persoonlijk belangen of reputatiegewin. Ik treed in deze werkgroep als afgevaardigde van de beroepsgroep KNGF en zal enkel de kennis vanuit ChronischZorgnet (voorheen ClaudicatioNet) meebrengen.	Chronisch ZorgNet is op de hoogte en ondersteund de inbreng in deze werkgroep. Vanuit KNGF is de duidelijke opdracht om alle fysiotherapeuten met de specialisatie PAV te vertegenwoordigen. Dit zal naar verwachting ook beter zichtbaar worden bij het invoeren van het aantekenregister Vaat (als onderdeel van deelregistratie hart-vaat-long-fysiotherapeut). Er is een open en prettige communicatie onderling en geen belangenverstrengeling.	Geen restricties voor deelname aan de richtlijn.
Rinske Loeffen	Internist vasculair geneeskundige	Richtlijn Perifeer arterieel vaatlijden	* Redactielid Focus Vasculair (onbetaald) * Werkgroep Tabaksontmoediging NVALT (onbetaald) * Werkgroep SKMS project Stop met Roken Zorg (onbetaald) * Werkgroep Acute boekje vasculaire geneeskunde (onbetaald).	Geen.	Geen.	Geen.	Geen.	Geen.	Geen restricties voor deelname aan de richtlijn.
Sanne de Boer	Interventieradioloog	Richtlijn Perifeer arterieel vaatlijden	* Verschillende wetenschappelijke en beleidscommissies binnen de NVIR (onbetaald) * Institutioneel contract met Brainlab voor consultant werkzaamheden * Institutioneel contract met MUMC/CTCM * Incidenteel consultant werkzaamheden voor Philips, ook via institutioneel contract.	Zie nevenwerkzaamheden.	Geen.		Geen.	Geen.	Geen restricties. Onderwerp van advieswerk valt buiten de afbakening van de richtlijn.
Çagdas Ünlü	Vaatchirurg	Richtlijn Perifeer arterieel vaatlijden	Projectleider CLEARPATH, studie na antistolling na endovasculaire behandeling ZonMw subsidie	Geen.	Geen.	ZonMw (Clearpath)	Geen.	Geen.	Geen restricties voor deelname aan de richtlijn.
Daniel van den Heuvel	Interventie Radioloog	Richtlijn Perifeer arterieel vaatlijden	Proctor voor bedrijf LimFlow SA, Parijs. Betaald. Adjudicator voor Bioreact studie, Biotronic. Betaald.	Zie nevenwerkzaamheden. Verder geen persoonlijke financiële belangen.	Geen.	Philips/Illumenate BTK PMS. Effectiviteit en veiligheid van de Stellarex .014 Ballon bij patiënten met kritieke ischemie ->ja. Micromedical/Heal study, PMS. Effectiviteit en veiligheid van de Microstent bij patiënten met kritieke ischemie -> ja. Philips/REPEAT study. Reproduceerbaarheid van 2D perfusie angiografie-> ja.	Geen.	Geen.	Geen restricties voor deelname aan de richtlijn.
Jorg de Bruin	Vaatchirurg	Richtlijn Perifeer arterieel vaatlijden	EMC; Klinisch en wetenschappelijk werk vaatchirurgie in academisch ziekenhuis	Geen conflict of specifiek belang.	Geen.	Geen.	Geen.	Geen.	Geen restricties voor deelname aan de richtlijn.
Ilse Verstraaten	Beleidsadviseur Harteraard (betaald)	Richtlijn Perifeer arterieel vaatlijden	Geen.	Geen.	Geen.	Geen.	Geen.	Geen.	Geen restricties voor deelname aan de richtlijn.
Gilaine Kleian	Junior projectmedewerker, Harteraad	Richtlijn Perifeer arterieel vaatlijden	Geen.	Geen.	Geen.	Geen.	Geen.	Geen.	Geen restricties voor deelname aan de richtlijn.
Barend Mees	Vaatchirurg	Richtlijn Perifeer arterieel vaatlijden	* Secretaris bestuur Nederlandse Vereniging voor Vaatchirurgie * Lid Commissie Richtlijnen NVvH * Council Member European Society for Vascular Surgery * Member ESVS Steering Guideline Committee * Director European Vascular Course. * Bestuur Stichting Drie Lichten * Lid Onderzoekspijler Dutch Cardiovascular Alliance * Lid adviesraad Marfan patienten * Consultancy werkzaamheden voor Philips, Bentley Innomed.	Geen.	Geen.	* Regmed XB: Cardiovascular Moonshot (Moonshot leader) * EU-Horizon 2020: PAPA-ARTIS (local PI) * InScIte: XS-graft (onderzoeksleider) * Philips: SAVER-registry (National PI) * ID3: Supersurg trial (local PI) * Cook: Zephyr registry (local PI) * Philips: FORS registry (local co-PI) * ZonMw: GENPAD study (local PI)	*Ontwikkelaar van de mazeBox, een training tool voor endovasculaire technieken.	Geen.	Geen restricties voor deelname aan richtlijn. Genoemde onderzoek valt buiten de afbakening van de richtlijn.

Inbreng patiëntenperspectief

Er werd aandacht besteed aan het patiëntenperspectief door het uitnodigen van Harteraad voor de schriftelijke knelpuntenanalyse. Het verslag hiervan is besproken in de werkgroep. De verkregen input is meegenomen bij het opstellen van de uitgangsvragen, de keuze voor de uitkomstmaten en bij het opstellen van de overwegingen. De conceptrichtlijn is tevens voor commentaar voorgelegd aan de deelnemers van de schriftelijke knelpuntenanalyse en de eventueel aangeleverde commentaren zijn bekeken en verwerkt.

Kwalitatieve raming van mogelijke financiële gevolgen in het kader van de Wkkgz

Bij de richtlijnmodule is conform de Wet kwaliteit, klachten en geschillen zorg (Wkkgz) een kwalitatieve raming uitgevoerd om te beoordelen of de aanbevelingen mogelijk leiden tot substantiële financiële gevolgen. Bij het uitvoeren van deze beoordeling is de richtlijnmodule op verschillende domeinen getoetst.

Module	Uitkomst raming	Toelichting
Module: Femoro-popliteaal: Endovasculaire behandeling vs bypasschirurgie	Geen substantiële financiële gevolgen	Uit de toetsing volgt dat de aanbevelingen mogelijk een kostenbesparend effect hebben door de principes van stepped care te volgen.

Werkwijze

AGREE

Deze richtlijnmodule is opgesteld conform de eisen vermeld in het rapport Medisch Specialistische Richtlijnen 2.0 van de adviescommissie Richtlijnen van de Raad Kwaliteit. Dit rapport is gebaseerd op het AGREE II instrument (Appraisal of Guidelines for Research & Evaluation II; Brouwers, 2010).

Knelpuntenanalyse en uitgangsvragen

Tijdens de voorbereidende fase inventariseerde de werkgroep de knelpunten in de zorg voor patiënten met (chronisch) perifeer arterieel vaatlijden van de onderste extremiteit(en). Tevens zijn er knelpunten aangedragen via een schriftelijke knelpuntenanalyse. Een verslag hiervan is opgenomen onder aanverwante producten.

Op basis van de uitkomsten van de knelpuntenanalyse zijn door de werkgroep concept-uitgangsvragen opgesteld en definitief vastgesteld.

Uitkomstmaten

Na het opstellen van de zoekvraag behorende bij de uitgangsvraag inventariseerde de werkgroep welke uitkomstmaten voor de patiënt relevant zijn, waarbij zowel naar gewenste als ongewenste effecten werd gekeken. Hierbij werd een maximum van acht uitkomstmaten gehanteerd. De werkgroep waardeerde deze uitkomstmaten volgens hun relatieve belang bij de besluitvorming rondom aanbevelingen, als cruciaal (kritiek voor de besluitvorming), belangrijk (maar niet cruciaal) en onbelangrijk. Tevens definieerde de werkgroep tenminste voor de cruciale uitkomstmaten welke verschillen zij klinisch (patiënt) relevant vonden.

Methode literatuursamenvatting

Een uitgebreide beschrijving van de strategie voor zoeken en selecteren van literatuur is te vinden onder ‘Zoeken en selecteren’ onder Onderbouwing. Indien mogelijk werd de data uit verschillende studies gepoold in een random-effects model. [Review Manager 5.4] werd gebruikt voor de statistische analyses. De beoordeling van de kracht van het wetenschappelijke bewijs wordt hieronder toegelicht.

Beoordelen van de kracht van het wetenschappelijke bewijs

De kracht van het wetenschappelijke bewijs werd bepaald volgens de GRADE-methode. GRADE staat voor ‘Grading Recommendations Assessment, Development and Evaluation’ (zie http://www.gradeworkinggroup.org/). De basisprincipes van de GRADE-methodiek zijn: het benoemen en prioriteren van de klinisch (patiënt) relevante uitkomstmaten, een systematische review per uitkomstmaat, en een beoordeling van de bewijskracht per uitkomstmaat op basis van de acht GRADE-domeinen (domeinen voor downgraden: risk of bias, inconsistentie, indirectheid, imprecisie, en publicatiebias; domeinen voor upgraden: dosis-effect relatie, groot effect, en residuele plausibele confounding).

GRADE onderscheidt vier gradaties voor de kwaliteit van het wetenschappelijk bewijs: hoog, redelijk, laag en zeer laag. Deze gradaties verwijzen naar de mate van zekerheid die er bestaat over de literatuurconclusie, in het bijzonder de mate van zekerheid dat de literatuurconclusie de aanbeveling adequaat ondersteunt (Schünemann, 2013; Hultcrantz, 2017).

GRADE	Definitie
Hoog	er is hoge zekerheid dat het ware effect van behandeling dichtbij het geschatte effect van behandeling ligt; het is zeer onwaarschijnlijk dat de literatuurconclusie klinisch relevant verandert wanneer er resultaten van nieuw grootschalig onderzoek aan de literatuuranalyse worden toegevoegd.
Redelijk	er is redelijke zekerheid dat het ware effect van behandeling dichtbij het geschatte effect van behandeling ligt; het is mogelijk dat de conclusie klinisch relevant verandert wanneer er resultaten van nieuw grootschalig onderzoek aan de literatuuranalyse worden toegevoegd.
Laag	er is lage zekerheid dat het ware effect van behandeling dichtbij het geschatte effect van behandeling ligt; er is een reële kans dat de conclusie klinisch relevant verandert wanneer er resultaten van nieuw grootschalig onderzoek aan de literatuuranalyse worden toegevoegd.
Zeer laag	er is zeer lage zekerheid dat het ware effect van behandeling dichtbij het geschatte effect van behandeling ligt; de literatuurconclusie is zeer onzeker.

Bij het beoordelen (graderen) van de kracht van het wetenschappelijk bewijs in richtlijnen volgens de GRADE-methodiek spelen grenzen voor klinische besluitvorming een belangrijke rol (Hultcrantz, 2017). Dit zijn de grenzen die bij overschrijding aanleiding zouden geven tot een aanpassing van de aanbeveling. Om de grenzen voor klinische besluitvorming te bepalen moeten alle relevante uitkomstmaten en overwegingen worden meegewogen. De grenzen voor klinische besluitvorming zijn daarmee niet één op één vergelijkbaar met het minimaal klinisch relevant verschil (Minimal Clinically Important Difference, MCID). Met name in situaties waarin een interventie geen belangrijke nadelen heeft en de kosten relatief laag zijn, kan de grens voor klinische besluitvorming met betrekking tot de effectiviteit van de interventie bij een lagere waarde (dichter bij het nuleffect) liggen dan de MCID (Hultcrantz, 2017).

Overwegingen (van bewijs naar aanbeveling)

Om te komen tot een aanbeveling zijn naast (de kwaliteit van) het wetenschappelijke bewijs ook andere aspecten belangrijk en worden meegewogen, zoals aanvullende argumenten uit bijvoorbeeld de biomechanica of fysiologie, waarden en voorkeuren van patiënten, kosten (middelenbeslag), aanvaardbaarheid, haalbaarheid en implementatie. Deze aspecten zijn systematisch vermeld en beoordeeld (gewogen) onder het kopje ‘Overwegingen’ en kunnen (mede) gebaseerd zijn op expert opinion. Hierbij is gebruik gemaakt van een gestructureerd format gebaseerd op het evidence-to-decision framework van de internationale GRADE Working Group (Alonso-Coello, 2016a; Alonso-Coello 2016b). Dit evidence-to-decision framework is een integraal onderdeel van de GRADE methodiek.

Formuleren van aanbevelingen

De aanbevelingen geven antwoord op de uitgangsvraag en zijn gebaseerd op het beschikbare wetenschappelijke bewijs en de belangrijkste overwegingen, en een weging van de gunstige en ongunstige effecten van de relevante interventies. De kracht van het wetenschappelijk bewijs en het gewicht dat door de werkgroep wordt toegekend aan de overwegingen, bepalen samen de sterkte van de aanbeveling. Conform de GRADE-methodiek sluit een lage bewijskracht van conclusies in de systematische literatuuranalyse een sterke aanbeveling niet a priori uit, en zijn bij een hoge bewijskracht ook zwakke aanbevelingen mogelijk (Agoritsas, 2017; Neumann, 2016). De sterkte van de aanbeveling wordt altijd bepaald door weging van alle relevante argumenten tezamen. De werkgroep heeft bij elke aanbeveling opgenomen hoe zij tot de richting en sterkte van de aanbeveling zijn gekomen.

In de GRADE-methodiek wordt onderscheid gemaakt tussen sterke en zwakke (of conditionele) aanbevelingen. De sterkte van een aanbeveling verwijst naar de mate van zekerheid dat de voordelen van de interventie opwegen tegen de nadelen (of vice versa), gezien over het hele spectrum van patiënten waarvoor de aanbeveling is bedoeld. De sterkte van een aanbeveling heeft duidelijke implicaties voor patiënten, behandelaars en beleidsmakers (zie onderstaande tabel). Een aanbeveling is geen dictaat, zelfs een sterke aanbeveling gebaseerd op bewijs van hoge kwaliteit (GRADE gradering HOOG) zal niet altijd van toepassing zijn, onder alle mogelijke omstandigheden en voor elke individuele patiënt.

Implicaties van sterke en zwakke aanbevelingen voor verschillende richtlijngebruikers

	Sterke aanbeveling	Zwakke (conditionele) aanbeveling
Voor patiënten	De meeste patiënten zouden de aanbevolen interventie of aanpak kiezen en slechts een klein aantal niet.	Een aanzienlijk deel van de patiënten zouden de aanbevolen interventie of aanpak kiezen, maar veel patiënten ook niet.
Voor behandelaars	De meeste patiënten zouden de aanbevolen interventie of aanpak moeten ontvangen.	Er zijn meerdere geschikte interventies of aanpakken. De patiënt moet worden ondersteund bij de keuze voor de interventie of aanpak die het beste aansluit bij zijn of haar waarden en voorkeuren.
Voor beleidsmakers	De aanbevolen interventie of aanpak kan worden gezien als standaardbeleid.	Beleidsbepaling vereist uitvoerige discussie met betrokkenheid van veel stakeholders. Er is een grotere kans op lokale beleidsverschillen.

Organisatie van zorg

In de knelpuntenanalyse en bij de ontwikkeling van de richtlijnmodule is expliciet aandacht geweest voor de organisatie van zorg: alle aspecten die randvoorwaardelijk zijn voor het verlenen van zorg (zoals coördinatie, communicatie, (financiële) middelen, mankracht en infrastructuur). Randvoorwaarden die relevant zijn voor het beantwoorden van deze specifieke uitgangsvraag zijn genoemd bij de overwegingen. Meer algemene, overkoepelende, of bijkomende aspecten van de organisatie van zorg worden behandeld in module 14 en 15.

Commentaar- en autorisatiefase

De conceptrichtlijnmodule werd aan de betrokken (wetenschappelijke) verenigingen en (patiënt) organisaties voorgelegd ter commentaar. De commentaren werden verzameld en besproken met de werkgroep. Naar aanleiding van de commentaren werd de conceptrichtlijnmodule aangepast en definitief vastgesteld door de werkgroep. De definitieve richtlijnmodule werd aan de deelnemende (wetenschappelijke) verenigingen en (patiënt) organisaties voorgelegd voor autorisatie en door hen geautoriseerd dan wel geaccordeerd.

Literatuur

Agoritsas T, Merglen A, Heen AF, Kristiansen A, Neumann I, Brito JP, Brignardello-Petersen R, Alexander PE, Rind DM, Vandvik PO, Guyatt GH. UpToDate adherence to GRADE criteria for strong recommendations: an analytical survey. BMJ Open. 2017 Nov 16;7(11):e018593. doi: 10.1136/bmjopen-2017-018593. PubMed PMID: 29150475; PubMed Central PMCID: PMC5701989.

Alonso-Coello P, Schünemann HJ, Moberg J, Brignardello-Petersen R, Akl EA, Davoli M, Treweek S, Mustafa RA, Rada G, Rosenbaum S, Morelli A, Guyatt GH, Oxman AD; GRADE Working Group. GRADE Evidence to Decision (EtD) frameworks: a systematic and transparent approach to making well informed healthcare choices. 1: Introduction. BMJ. 2016 Jun 28;353:i2016. doi: 10.1136/bmj.i2016. PubMed PMID: 27353417.

Alonso-Coello P, Oxman AD, Moberg J, Brignardello-Petersen R, Akl EA, Davoli M, Treweek S, Mustafa RA, Vandvik PO, Meerpohl J, Guyatt GH, Schünemann HJ; GRADE Working Group. GRADE Evidence to Decision (EtD) frameworks: a systematic and transparent approach to making well informed healthcare choices. 2: Clinical practice guidelines. BMJ. 2016 Jun 30;353:i2089. doi: 10.1136/bmj.i2089. PubMed PMID: 27365494.

Brouwers MC, Kho ME, Browman GP, Burgers JS, Cluzeau F, Feder G, Fervers B, Graham ID, Grimshaw J, Hanna SE, Littlejohns P, Makarski J, Zitzelsberger L; AGREE Next Steps Consortium. AGREE II: advancing guideline development, reporting and evaluation in health care. CMAJ. 2010 Dec 14;182(18):E839-42. doi: 10.1503/cmaj.090449. Epub 2010 Jul 5. Review. PubMed PMID: 20603348; PubMed Central PMCID: PMC3001530.

Hultcrantz M, Rind D, Akl EA, Treweek S, Mustafa RA, Iorio A, Alper BS, Meerpohl JJ, Murad MH, Ansari MT, Katikireddi SV, Östlund P, Tranæus S, Christensen R, Gartlehner G, Brozek J, Izcovich A, Schünemann H, Guyatt G. The GRADE Working Group clarifies the construct of certainty of evidence. J Clin Epidemiol. 2017 Jul;87:4-13. doi: 10.1016/j.jclinepi.2017.05.006. Epub 2017 May 18. PubMed PMID: 28529184; PubMed Central PMCID: PMC6542664.

Medisch Specialistische Richtlijnen 2.0 (2012). Adviescommissie Richtlijnen van de Raad Kwalitieit. http://richtlijnendatabase.nl/over_deze_site/over_richtlijnontwikkeling.html

Neumann I, Santesso N, Akl EA, Rind DM, Vandvik PO, Alonso-Coello P, Agoritsas T, Mustafa RA, Alexander PE, Schünemann H, Guyatt GH. A guide for health professionals to interpret and use recommendations in guidelines developed with the GRADE approach. J Clin Epidemiol. 2016 Apr;72:45-55. doi: 10.1016/j.jclinepi.2015.11.017. Epub 2016 Jan 6. Review. PubMed PMID: 26772609.

Schünemann H, Brożek J, Guyatt G, et al. GRADE handbook for grading quality of evidence and strength of recommendations. Updated October 2013. The GRADE Working Group, 2013. Available from http://gdt.guidelinedevelopment.org/central_prod/_design/client/handbook/handbook.html.

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Richtlijnendatabase

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Uitgangsvraag

Aanbeveling

Overwegingen

Onderbouwing

Achtergrond

Conclusies / Summary of Findings

Samenvatting literatuur

Zoeken en selecteren

Referenties

Evidence tabellen

Verantwoording

Autorisatiedatum en geldigheid

Initiatief en autorisatie

Algemene gegevens

Samenstelling werkgroep

Belangenverklaringen

Inbreng patiëntenperspectief

Werkwijze

Zoekverantwoording

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