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Editor's Choice – An Updated Systematic Review and Meta-analysis of Outcomes Following Eversion vs. Conventional Carotid Endarterectomy in Randomised Controlled Trials and Observational Studies

Open ArchivePublished:February 06, 2018DOI:https://doi.org/10.1016/j.ejvs.2017.12.025

      Introduction

      A 2011 meta-analysis comparing eversion (eCEA) with conventional (cCEA) carotid endarterectomy in 16,251 patients concluded that eCEA was associated with lower rates of peri-operative stroke and late occlusion compared with cCEA. However, randomised controlled trials (RCTs) showed no difference in outcomes. Since then, the literature contains outcome data on 49,500 patients undergoing eCEA or cCEA. An updated meta-analysis was performed to establish whether eCEA confers significant benefit over cCEA.

      Methods

      This was a systematic review of PubMed/Medline, Embase, and Cochrane databases for RCTs and observational studies (OSs) comparing eCEA with cCEA. A sensitivity analysis was also performed using data from OSs with a Newcastle-Ottawa score >5.

      Results

      There were 25 eligible studies (5 RCTs, 20 OSs) involving 49,500 CEAs (16,249 eCEAs; 33,251 cCEAs). RCT data: Compared with cCEA, eCEA did not confer significant reductions in 30 day stroke, death, death/stroke, death/stroke/MI, or neck haematoma. However, eCEA was associated with reduced late restenosis (OR 0.40; p = .001). OS data: eCEA was associated with significant reductions in 30 day death (OR 0.46; p < .0001), stroke (OR 0.58; p < .0001), death/stroke (OR 0.52; p < .0001), death/stroke/MI (OR 0.50; p < .0001), and late restenosis (OR 0.49; p = .032) compared with cCEA. RCT and OS data combined: eCEA was associated with significant reductions in 30 day death (OR 0.55; p < .0001), stroke (OR 0.63; p = .004), death/stroke (OR 0.58; p < .0001), and late restenosis (OR 0.45; p = .004) compared with cCEA. eCEA vs. patched cCEA (RCT and OS data): There were no differences between the two procedures except for neck haematoma, where eCEA was better than patched cCEA.

      Conclusions

      Using combined RCT and OS data, eCEA was superior to cCEA regarding peri-operative outcomes (stroke, death, death/stroke) and late restenosis, but was similar to patched CEA in both early and late outcomes. This updated meta-analysis suggests that early and late outcomes following cCEA are similar to eCEA, provided the arteriotomy is patched.

      Keywords

      Using combined data from randomised controlled trials and observational studies, eversion carotid endarterectomy (eCEA) was superior to conventional CEA (cCEA) regarding peri-operative outcomes (death, stroke, death/stroke) and late (>50%) restenosis. However, when eCEA outcomes were compared with outcomes after patched CEA, there were no significant differences. This updated meta-analysis suggests that early and late outcomes following cCEA are similar to eCEA, provided the arteriotomy is patched.

      Introduction

      Eversion (eCEA) and conventional carotid endarterectomy (cCEA) are the commonest techniques for performing CEA. Arteriotomy closure following cCEA is achieved by either direct closure (dCEA) or by patch angioplasty (pCEA). The main advantage of eCEA is that no prosthetic material is used. However, eCEA is limited by an inability to insert a shunt until the plaque has been removed and by a significantly higher incidence of post-CEA hypertension.
      • Demirel S.
      • Goossen K.
      • Bruijnen H.
      • Probst P.
      • Bockler D.
      Systematic review and meta-analysis of postcarotid endarterectomy hypertension after eversion versus conventional carotid endarterectomy.
      On the other hand, dCEA is associated with higher rates of peri-operative stroke, peri-operative thrombosis and higher rates of late restenosis and late ipsilateral stroke compared with routine pCEA,
      • Rerkasem K.
      • Rothwell P.M.
      Systematic review of randomized controlled trials of patch angioplasty versus primary closure and different types of patch materials during carotid endarterectomy.
      • Ren S.
      • Li X.
      • Wen J.
      • Zhang W.
      • Liu P.
      Systematic review of randomized controlled trials of different types of patch materials during carotid endarterectomy.
      while pCEA is vulnerable to late prosthetic patch infection in about 1% of patients.
      • Naylor A.R.
      • Payne D.
      • London N.J.
      • Thompson M.M.
      • Dennis M.S.
      • Sayers R.D.
      • et al.
      Prosthetic patch infection after carotid endarterectomy.
      Several randomised controlled trials (RCTs) and observational studies (OSs) have compared eCEA with cCEA with regard to short-term outcomes (30 day stroke, 30 day death/stroke, 30 day death/stroke/myocardial infarction [MI], cranial nerve injury [CNI], neck haematoma, and 30 day internal carotid artery [ICA] thrombosis) as well as late outcomes (late restenosis, late ipsilateral stroke). A 2001 Cochrane systematic review of five RCTs comparing eCEA (n = 1303) with cCEA (n = 1286) reported no significant differences in peri-operative stroke (1.4% vs. 2.0%), peri-operative death (0.6% vs. 0.7%), peri-operative stroke and/or death (1.7% vs. 2.6%), peri-operative MI (0.5% vs. 0.6%), CNI (3.8% vs. 5.6%), and long-term stroke (1.4% vs. 1.7%).
      • Cao P.G.
      • de Rango P.
      • Zannetti S.
      • Giordano G.
      • Ricci S.
      • Celani M.G.
      Eversion versus conventional carotid endarterectomy for preventing stroke.
      However, the meta-analysis suggested that eCEA was associated with significantly lower rates of restenosis >50%, compared with cCEA (2.5% vs. 5.2%, p = .00036).
      • Cao P.G.
      • de Rango P.
      • Zannetti S.
      • Giordano G.
      • Ricci S.
      • Celani M.G.
      Eversion versus conventional carotid endarterectomy for preventing stroke.
      However, when pCEA was compared with eCEA, there were no significant differences in late restenosis.
      • Cao P.G.
      • de Rango P.
      • Zannetti S.
      • Giordano G.
      • Ricci S.
      • Celani M.G.
      Eversion versus conventional carotid endarterectomy for preventing stroke.
      In 2011, an updated systematic review reported early and late outcomes following 8530 eCEAs and 7721 cCEAs.
      • Antonopoulos C.N.
      • Kakisis J.D.
      • Sergentanis T.N.
      • Liapis C.D.
      Eversion versus conventional carotid endarterectomy: a meta-analysis of randomised and non-randomised studies.
      This meta-analysis now included data from 7 RCTs and 15 OSs and reported that eCEA was associated with significant reductions in peri-operative stroke (OR 0.46; 95% CI 0.35–0.62; p < .001) and peri-operative death (OR 0.49; 95% CI 0.34–0.69; p < .001) compared with cCEA.
      • Antonopoulos C.N.
      • Kakisis J.D.
      • Sergentanis T.N.
      • Liapis C.D.
      Eversion versus conventional carotid endarterectomy: a meta-analysis of randomised and non-randomised studies.
      In addition, patients undergoing eCEA had significantly lower rates of late ICA occlusion (OR 0.48; 95% CI 0.25–0.90; p = .02) and late mortality (OR 0.76; 95% CI 0.61–0.94; p = .001).
      • Antonopoulos C.N.
      • Kakisis J.D.
      • Sergentanis T.N.
      • Liapis C.D.
      Eversion versus conventional carotid endarterectomy: a meta-analysis of randomised and non-randomised studies.
      Interestingly, with the exception of late ICA occlusion, each of these statistically significant differences were maintained in a further analysis comparing eCEA with pCEA.
      • Antonopoulos C.N.
      • Kakisis J.D.
      • Sergentanis T.N.
      • Liapis C.D.
      Eversion versus conventional carotid endarterectomy: a meta-analysis of randomised and non-randomised studies.
      Since the 2011 meta-analysis was published,
      • Antonopoulos C.N.
      • Kakisis J.D.
      • Sergentanis T.N.
      • Liapis C.D.
      Eversion versus conventional carotid endarterectomy: a meta-analysis of randomised and non-randomised studies.
      the literature now contains outcome data on 49,500 patients undergoing either eCEA or cCEA. Given the discordance between the findings of the 2001 and 2011 meta-analyses (especially that eCEA may be safer than pCEA), a further meta-analysis was undertaken to determine whether eCEA conferred significant benefit over cCEA. If true, this would support preferential use of eCEA in an increasing majority of patients.

      Materials and methods

      A systematic review was conducted according to the recommendations of the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement (Fig. 1).
      • Moher D.
      • Liberati A.
      • Tetzlaff J.
      • Altman D.G.
      PRISMA Group
      Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.
      PubMed/Medline, Embase, and the Cochrane databases were independently searched by two investigators (KIP, VR) from December 30, 2010 (end of study inclusion of the previous meta-analysis)
      • Antonopoulos C.N.
      • Kakisis J.D.
      • Sergentanis T.N.
      • Liapis C.D.
      Eversion versus conventional carotid endarterectomy: a meta-analysis of randomised and non-randomised studies.
      until February 1, 2017 to identify studies comparing short (30 day) and late outcomes following eCEA and cCEA. Only those studies reporting outcome data for both eCEA and cCEA were included. If there was any disagreement between the two investigators, this was resolved either by consensus discussion or via referral to a third party (ARN). Data abstraction was performed independently and the results were subsequently compared between investigators.
      By use of the mesh term “carotid endarterectomy” and application of a filter “from 2010/12/30 to 2017/02/01,” a total of 3011 reports was identified. The abstracts were read to identify studies comparing outcomes after eCEA and cCEA. Only English language reports were considered.
      The outcomes/endpoints that were compared between the two techniques included: (i) 30 day stroke; (ii) 30 day death; (iii) 30 day MI; (iv) 30 day stroke/death; (v) 30 day stroke/death/MI; (vi) 30 day neck haematoma; (vii) 30 day CNI; and (vii) late >50% restenosis.

      Statistical analyses

      Statistical analyses were performed using the R package for Microsoft Windows (version 3.0). Random and fixed effects meta-analyses were performed using the proportions of patients who experienced the outcome of interest in each case, as described above (stroke – 30 day or late, >50% restenosis, death, MI, neck haematoma). ORs with 95% CI were calculated for each study included in the final synthesis to assess the association between each type of carotid intervention and subsequent outcomes. Results from the various studies were combined in a stepwise manner: initially ORs were combined for both RCTs and OSs; subsequently, data were analysed separately for RCTs and OSs. For those studies where one arm reported no post-operative events but another arm reported at least one event, a fixed factor of 0.5 was added to cells of the study results with zero events to calculate an appropriate OR and allow synthesis. This type of continuity correction is a well established approach to incorporate zero event studies and 0.5 is the commonest choice of correction factor. ORs were then combined using meta-analysis (fixed and random effects models, where appropriate). Inter-study heterogeneity was analysed using the I2 statistic in all analyses. This describes the percentage of total variation across studies because of heterogeneity, rather than chance or random error and is a recognised method of quantifying heterogeneity in literature synthesis. An I2 value ≥ 50% reflects significant heterogeneity owing to real differences in study populations, protocols, interventions, and outcomes. Based on the result of the I2 statistic, a fixed effects model was used to combine studies if I2 was <50% and a random effects model if I2 was ≥50%. A p value < .05 was considered to be statistically significant.
      To minimise bias through the inclusion of poorer quality OSs, a sensitivity analysis was also performed which used data from OSs in which the Newcastle-Ottawa score (NOS) was >5 (i.e. studies deemed better quality methodologically). Given the nature of the studies included in the literature synthesis (OSs combined with RCTs), the significant heterogeneity in most of these series (as reflected by the I2 statistics in most instances), and the significant differences in terms of the size/effect among the observational cohorts, weighted proportions were reported for all analyses.

      Results

      The systematic review

      By use of the mesh term “carotid endarterectomy” and application of a filter “from 2010/12/30 to 2017/02/01,” a total of 3011 reports were identified. After duplicate publications were excluded, 3010 reports were screened, after which 1170 studies were excluded (reasons for exclusion are given in Fig. 1). A total of 1840 articles were subsequently assessed for eligibility, following which 1815 articles were excluded (Fig. 1). This left 25 papers for qualitative and quantitative synthesis (Table 1).
      • Menyhei G.
      • Björck M.
      • Beiles B.
      • Halbakken E.
      • Jensen L.P.
      • Lees T.
      • et al.
      Outcome following carotid endarterectomy: lessons learned from a large international vascular registry.
      • Demirel S.
      • Attigah N.
      • Bruijnen H.
      • Ringleb P.
      • Eckstein H.H.
      • Fraedrich G.
      • et al.
      SPACE Investigators
      Multicenter experience on eversion versus conventional carotid endarterectomy in symptomatic carotid artery stenosis: observations from the Stent-Protected Angioplasty Versus Carotid Endarterectomy (SPACE-1) trial.
      • Lee J.H.
      • Suh B.Y.
      Comparative results of conventional and eversion carotid endarterectomy.
      • Yasa H.
      • Akyuz M.
      • Yakut N.
      • Aslan O.
      • Akyuz D.
      • Ozcem B.
      • et al.
      Comparison of two surgical techniques for carotid endarterectomy: conventional and eversion.
      • Schneider J.R.
      • Helenowski I.B.
      • Jackson C.R.
      • Verta M.J.
      • Zamor K.C.
      • Patel N.H.
      • et al.
      Society for Vascular Surgery Vascular Quality Initiative and the Mid-America Vascular Study Group
      A comparison of results with eversion versus conventional carotid endarterectomy from the Vascular Quality Initiative and the Mid-America Vascular Study Group.
      • Ben Ahmed S.
      • Daniel G.
      • Benezit M.
      • Bailly P.
      • Aublet-Cuvelier B.
      • Mulliez A.
      • et al.
      Does the technique of carotid endarterectomy determine postoperative hypertension?.
      • Ballotta E.
      • Da Giau G.
      • Saladini M.
      • Abbruzzese E.
      • Renon L.
      • Toniato A.
      Carotid endarterectomy with patch closure versus carotid eversion endarterectomy and reimplantation: a prospective randomized study.
      • Ballotta E.
      • Renon L.
      • Da Giau G.
      • Toniato A.
      • Baracchini C.
      • Abbruzzese E.
      • et al.
      A prospective randomized study on bilateral carotid endarterectomy: patching versus eversion.
      • Brothers T.E.
      Initial experience with eversion carotid endarterectomy: absence of a learning curve for the first 100 patients.
      • Cao P.
      • Giordano G.
      • De Rango P.
      • Caporali S.
      • Lenti M.
      • Ricci S.
      • et al.
      Eversion versus conventional carotid endarterectomy: a prospective study.
      • Cao P.
      • Giordano G.
      • De Rango P.
      • Zannetti S.
      • Chiesa R.
      • Coppi G.
      • et al.
      A randomized study on eversion versus standard carotid endarterectomy: study design and preliminary results: the Everest Trial.
      • Crawford R.S.
      • Chung T.K.
      • Hodgman T.
      • Pedraza J.D.
      • Corey M.
      • Cambria R.P.
      Restenosis after eversion vs patch closure carotid endarterectomy.
      • Economopoulos K.J.
      • Gentile A.T.
      • Berman S.S.
      Comparison of carotid endarterectomy using primary closure, patch closure, and eversion techniques.
      • Entz L.
      • Járányi Z.
      • Nemes A.
      Comparison of perioperative results obtained with carotid eversion endarterectomy and with conventional patch plasty.
      • Green R.M.
      • Greenberg R.
      • Illig K.
      • Shortell C.
      • Ouriel K.
      Eversion endarterectomy of the carotid artery: technical considerations and recurrent stenoses.
      • Katras T.
      • Baltazar U.
      • Rush D.S.
      • Sutterfield W.C.
      • Harvill L.M.
      • Stanton Jr., P.E.
      Durability of eversion carotid endarterectomy: comparison with primary closure and carotid patch angioplasty.
      • Kieny R.
      • Hirsch D.
      • Seiller C.
      • Thiranos J.C.
      • Petit H.
      Does carotid eversion endarterectomy and reimplantation reduce the risk of restenosis?.
      • Littooy F.N.
      • Gagovic V.
      • Sandu C.
      • Mansour A.
      • Kang S.
      • Greisler H.P.
      Comparison of standard carotid endarterectomy with Dacron patch angioplasty versus eversion carotid endarterectomy during a 4-year period.
      • Markovic D.M.
      • Davidovic L.B.
      • Cvetkovic D.D.
      • Maksimovic Z.V.
      • Markovic D.Z.
      • Jadranin D.B.
      Single-center prospective, randomized analysis of conventional and eversion carotid endarterectomy.
      • Peiper C.
      • Nowack J.
      • Ktenidis K.
      • Reifenhäuser W.
      • Keresztury G.
      • Horsch S.
      Eversion endarterectomy versus open thromboendarterectomy and patch plasty for the treatment of internal carotid artery stenosis.
      • Radak D.
      • Radević B.
      • Sternić N.
      • Vucurević G.
      • Petrović B.
      • Ilijevski N.
      • et al.
      Single center experience on eversion versus standard carotid endarterectomy: a prospective non-randomized study.
      • Shah D.M.
      • Darling 3rd, R.C.
      • Chang B.B.
      • Paty P.S.
      • Kreienberg P.B.
      • Lloyd W.E.
      • et al.
      Carotid endarterectomy by eversion technique: its safety and durability.
      • Vanmaele R.G.
      • Van Schil P.E.
      • DeMaeseneer M.G.
      • Meese G.
      • Lehert P.
      • Van Look R.F.
      Division-endarterectomy-anastomosis of the internal carotid artery: a prospective randomized comparative study.
      • Winkler G.A.
      • Calligaro K.D.
      • Kolakowski S.
      • Doerr K.J.
      • McAffee-Bennett S.
      • Muller K.
      • et al.
      Comparison of intraoperative completion flowmeter versus duplex ultrasonography and contrast arteriography for carotid endarterectomy.
      • Wistrand J.
      • Mätzsch T.
      • Gonçalves I.
      • Riva L.
      • Dias N.V.
      Changing from conventional to eversion endarterectomy in carotid artery disease–a safe transition process in the short and long term.
      Table 1List of the studies included in the meta-analysis with the short and long-term outcomes investigated.
      Study (year)TotaleCEAcCEADeathStrokeMIDeath/strokeDeath/stroke/MIMean follow-up (months)RestenosisCranial nerve injuryNeck Haematoma
      Ballotta
      • Ballotta E.
      • Da Giau G.
      • Saladini M.
      • Abbruzzese E.
      • Renon L.
      • Toniato A.
      Carotid endarterectomy with patch closure versus carotid eversion endarterectomy and reimplantation: a prospective randomized study.
      (1999)
      RCT.
      336169167p34 (1–69)
      Results presented as mean (range).
      Ballotta
      • Ballotta E.
      • Renon L.
      • Da Giau G.
      • Toniato A.
      • Baracchini C.
      • Abbruzzese E.
      • et al.
      A prospective randomized study on bilateral carotid endarterectomy: patching versus eversion.
      (2000)
      RCT.
      1366868pNMNM40 (6–69)
      Results presented as mean (range).
      Brothers
      • Brothers T.E.
      Initial experience with eversion carotid endarterectomy: absence of a learning curve for the first 100 patients.
      (2005)
      200100100p36NMNM
      Cao
      • Cao P.
      • Giordano G.
      • De Rango P.
      • Caporali S.
      • Lenti M.
      • Ricci S.
      • et al.
      Eversion versus conventional carotid endarterectomy: a prospective study.
      (1997)
      514274118p; 122dcNMNM28 (12–54)
      Results presented as mean (range).
      NMNM
      Cao
      • Cao P.
      • Giordano G.
      • De Rango P.
      • Zannetti S.
      • Chiesa R.
      • Coppi G.
      • et al.
      A randomized study on eversion versus standard carotid endarterectomy: study design and preliminary results: the Everest Trial.
      (1998)
      RCT.
      1353678256p; 419dc33 (12–55)
      Results presented as mean (range).
      Crawford
      • Crawford R.S.
      • Chung T.K.
      • Hodgman T.
      • Pedraza J.D.
      • Corey M.
      • Cambria R.P.
      Restenosis after eversion vs patch closure carotid endarterectomy.
      (2007)
      290135155 p55 (12–140)
      Results presented as mean (range).
      Economopoulos
      • Economopoulos K.J.
      • Gentile A.T.
      • Berman S.S.
      Comparison of carotid endarterectomy using primary closure, patch closure, and eversion techniques.
      (1999)
      19033142p; 15dc16 (0–48)
      Results presented as mean (range).
      Entz
      • Entz L.
      • Járányi Z.
      • Nemes A.
      Comparison of perioperative results obtained with carotid eversion endarterectomy and with conventional patch plasty.
      (1997)
      1454739715pNMNM36NMNMNM
      Green
      • Green R.M.
      • Greenberg R.
      • Illig K.
      • Shortell C.
      • Ouriel K.
      Eversion endarterectomy of the carotid artery: technical considerations and recurrent stenoses.
      (2000)
      274107167pNMNM12NM
      Katras
      • Katras T.
      • Baltazar U.
      • Rush D.S.
      • Sutterfield W.C.
      • Harvill L.M.
      • Stanton Jr., P.E.
      Durability of eversion carotid endarterectomy: comparison with primary closure and carotid patch angioplasty.
      (2001)
      322118107p; 97dc23 (6–42)
      Results presented as mean (range).
      Kieny
      • Kieny R.
      • Hirsch D.
      • Seiller C.
      • Thiranos J.C.
      • Petit H.
      Does carotid eversion endarterectomy and reimplantation reduce the risk of restenosis?.
      (1993)
      368212156dcNMNMNMNMNM44NMNM
      Littooy
      • Littooy F.N.
      • Gagovic V.
      • Sandu C.
      • Mansour A.
      • Kang S.
      • Greisler H.P.
      Comparison of standard carotid endarterectomy with Dacron patch angioplasty versus eversion carotid endarterectomy during a 4-year period.
      (2004)
      18964125pNMNM17 (3–42)
      Results presented as mean (range).
      NM
      Markovic
      • Markovic D.M.
      • Davidovic L.B.
      • Cvetkovic D.D.
      • Maksimovic Z.V.
      • Markovic D.Z.
      • Jadranin D.B.
      Single-center prospective, randomized analysis of conventional and eversion carotid endarterectomy.
      (2008)
      RCT.
      20110377p; 21dc38 (24–52)
      Results presented as mean (range).
      NM
      Peiper
      • Peiper C.
      • Nowack J.
      • Ktenidis K.
      • Reifenhäuser W.
      • Keresztury G.
      • Horsch S.
      Eversion endarterectomy versus open thromboendarterectomy and patch plasty for the treatment of internal carotid artery stenosis.
      (1999)
      863475388pNMNM31
      Radak
      • Radak D.
      • Radević B.
      • Sternić N.
      • Vucurević G.
      • Petrović B.
      • Ilijevski N.
      • et al.
      Single center experience on eversion versus standard carotid endarterectomy: a prospective non-randomized study.
      (2000)
      2806212468256 (6–92)
      Results presented as mean (range).
      Shah
      • Shah D.M.
      • Darling 3rd, R.C.
      • Chang B.B.
      • Paty P.S.
      • Kreienberg P.B.
      • Lloyd W.E.
      • et al.
      Carotid endarterectomy by eversion technique: its safety and durability.
      (1998)
      2723224973p; 401dc18 (1–52)
      Results presented as mean (range).
      Vanmaele
      • Vanmaele R.G.
      • Van Schil P.E.
      • DeMaeseneer M.G.
      • Meese G.
      • Lehert P.
      • Van Look R.F.
      Division-endarterectomy-anastomosis of the internal carotid artery: a prospective randomized comparative study.
      (1994)
      RCT.
      20010298pNM12 ± 0.8
      Results presented as mean ± standard deviation.
      NM
      Winkler
      • Winkler G.A.
      • Calligaro K.D.
      • Kolakowski S.
      • Doerr K.J.
      • McAffee-Bennett S.
      • Muller K.
      • et al.
      Comparison of intraoperative completion flowmeter versus duplex ultrasonography and contrast arteriography for carotid endarterectomy.
      (2006)
      1165165pNMNM18 (6–42)
      Results presented as mean (range).
      NMNMNM
      Wistrand
      • Wistrand J.
      • Mätzsch T.
      • Gonçalves I.
      • Riva L.
      • Dias N.V.
      Changing from conventional to eversion endarterectomy in carotid artery disease–a safe transition process in the short and long term.
      (2010)
      1717365p; 33dc76NMNM
      Ben Ahmed
      • Ben Ahmed S.
      • Daniel G.
      • Benezit M.
      • Bailly P.
      • Aublet-Cuvelier B.
      • Mulliez A.
      • et al.
      Does the technique of carotid endarterectomy determine postoperative hypertension?.
      (2015)
      560220340pNMNMNMNMNMNMNM
      Demirel
      • Demirel S.
      • Attigah N.
      • Bruijnen H.
      • Ringleb P.
      • Eckstein H.H.
      • Fraedrich G.
      • et al.
      SPACE Investigators
      Multicenter experience on eversion versus conventional carotid endarterectomy in symptomatic carotid artery stenosis: observations from the Stent-Protected Angioplasty Versus Carotid Endarterectomy (SPACE-1) trial.
      (2012)
      516206310p24NM
      Lee
      • Lee J.H.
      • Suh B.Y.
      Comparative results of conventional and eversion carotid endarterectomy.
      (2014)
      120576329.4 ± 23.5
      Results presented as mean ± standard deviation.
      NM
      Menyhei
      • Menyhei G.
      • Björck M.
      • Beiles B.
      • Halbakken E.
      • Jensen L.P.
      • Lees T.
      • et al.
      Outcome following carotid endarterectomy: lessons learned from a large international vascular registry.
      (2011)
      15,69853496226p; 4123dcNMNMNMNMNM
      Schneider
      • Schneider J.R.
      • Helenowski I.B.
      • Jackson C.R.
      • Verta M.J.
      • Zamor K.C.
      • Patel N.H.
      • et al.
      Society for Vascular Surgery Vascular Quality Initiative and the Mid-America Vascular Study Group
      A comparison of results with eversion versus conventional carotid endarterectomy from the Vascular Quality Initiative and the Mid-America Vascular Study Group.
      (2015)
      19,520236517,155NMNMNM12NM
      Yasa
      • Yasa H.
      • Akyuz M.
      • Yakut N.
      • Aslan O.
      • Akyuz D.
      • Ozcem B.
      • et al.
      Comparison of two surgical techniques for carotid endarterectomy: conventional and eversion.
      (2014)
      38017820226 (14–38)
      Results presented as mean (range).
      Total49,50016,24933,251
      eCEA = eversion carotid endarterectomy; cCEA = conventional carotid endarterectomy; MI = myocardial infarction; p = patch; dc = direct closure; √ = data included; NM = not mentioned.
      a RCT.
      b Results presented as mean (range).
      c Results presented as mean ± standard deviation.
      Of the 25 papers, 5 were RCTs
      • Ballotta E.
      • Da Giau G.
      • Saladini M.
      • Abbruzzese E.
      • Renon L.
      • Toniato A.
      Carotid endarterectomy with patch closure versus carotid eversion endarterectomy and reimplantation: a prospective randomized study.
      • Ballotta E.
      • Renon L.
      • Da Giau G.
      • Toniato A.
      • Baracchini C.
      • Abbruzzese E.
      • et al.
      A prospective randomized study on bilateral carotid endarterectomy: patching versus eversion.
      • Cao P.
      • Giordano G.
      • De Rango P.
      • Zannetti S.
      • Chiesa R.
      • Coppi G.
      • et al.
      A randomized study on eversion versus standard carotid endarterectomy: study design and preliminary results: the Everest Trial.
      • Markovic D.M.
      • Davidovic L.B.
      • Cvetkovic D.D.
      • Maksimovic Z.V.
      • Markovic D.Z.
      • Jadranin D.B.
      Single-center prospective, randomized analysis of conventional and eversion carotid endarterectomy.
      • Vanmaele R.G.
      • Van Schil P.E.
      • DeMaeseneer M.G.
      • Meese G.
      • Lehert P.
      • Van Look R.F.
      Division-endarterectomy-anastomosis of the internal carotid artery: a prospective randomized comparative study.
      while the remaining 20
      • Menyhei G.
      • Björck M.
      • Beiles B.
      • Halbakken E.
      • Jensen L.P.
      • Lees T.
      • et al.
      Outcome following carotid endarterectomy: lessons learned from a large international vascular registry.
      • Demirel S.
      • Attigah N.
      • Bruijnen H.
      • Ringleb P.
      • Eckstein H.H.
      • Fraedrich G.
      • et al.
      SPACE Investigators
      Multicenter experience on eversion versus conventional carotid endarterectomy in symptomatic carotid artery stenosis: observations from the Stent-Protected Angioplasty Versus Carotid Endarterectomy (SPACE-1) trial.
      • Lee J.H.
      • Suh B.Y.
      Comparative results of conventional and eversion carotid endarterectomy.
      • Yasa H.
      • Akyuz M.
      • Yakut N.
      • Aslan O.
      • Akyuz D.
      • Ozcem B.
      • et al.
      Comparison of two surgical techniques for carotid endarterectomy: conventional and eversion.
      • Schneider J.R.
      • Helenowski I.B.
      • Jackson C.R.
      • Verta M.J.
      • Zamor K.C.
      • Patel N.H.
      • et al.
      Society for Vascular Surgery Vascular Quality Initiative and the Mid-America Vascular Study Group
      A comparison of results with eversion versus conventional carotid endarterectomy from the Vascular Quality Initiative and the Mid-America Vascular Study Group.
      • Ben Ahmed S.
      • Daniel G.
      • Benezit M.
      • Bailly P.
      • Aublet-Cuvelier B.
      • Mulliez A.
      • et al.
      Does the technique of carotid endarterectomy determine postoperative hypertension?.
      • Brothers T.E.
      Initial experience with eversion carotid endarterectomy: absence of a learning curve for the first 100 patients.
      • Cao P.
      • Giordano G.
      • De Rango P.
      • Caporali S.
      • Lenti M.
      • Ricci S.
      • et al.
      Eversion versus conventional carotid endarterectomy: a prospective study.
      • Crawford R.S.
      • Chung T.K.
      • Hodgman T.
      • Pedraza J.D.
      • Corey M.
      • Cambria R.P.
      Restenosis after eversion vs patch closure carotid endarterectomy.
      • Economopoulos K.J.
      • Gentile A.T.
      • Berman S.S.
      Comparison of carotid endarterectomy using primary closure, patch closure, and eversion techniques.
      • Entz L.
      • Járányi Z.
      • Nemes A.
      Comparison of perioperative results obtained with carotid eversion endarterectomy and with conventional patch plasty.
      • Green R.M.
      • Greenberg R.
      • Illig K.
      • Shortell C.
      • Ouriel K.
      Eversion endarterectomy of the carotid artery: technical considerations and recurrent stenoses.
      • Katras T.
      • Baltazar U.
      • Rush D.S.
      • Sutterfield W.C.
      • Harvill L.M.
      • Stanton Jr., P.E.
      Durability of eversion carotid endarterectomy: comparison with primary closure and carotid patch angioplasty.
      • Kieny R.
      • Hirsch D.
      • Seiller C.
      • Thiranos J.C.
      • Petit H.
      Does carotid eversion endarterectomy and reimplantation reduce the risk of restenosis?.
      • Littooy F.N.
      • Gagovic V.
      • Sandu C.
      • Mansour A.
      • Kang S.
      • Greisler H.P.
      Comparison of standard carotid endarterectomy with Dacron patch angioplasty versus eversion carotid endarterectomy during a 4-year period.
      • Peiper C.
      • Nowack J.
      • Ktenidis K.
      • Reifenhäuser W.
      • Keresztury G.
      • Horsch S.
      Eversion endarterectomy versus open thromboendarterectomy and patch plasty for the treatment of internal carotid artery stenosis.
      • Radak D.
      • Radević B.
      • Sternić N.
      • Vucurević G.
      • Petrović B.
      • Ilijevski N.
      • et al.
      Single center experience on eversion versus standard carotid endarterectomy: a prospective non-randomized study.
      • Shah D.M.
      • Darling 3rd, R.C.
      • Chang B.B.
      • Paty P.S.
      • Kreienberg P.B.
      • Lloyd W.E.
      • et al.
      Carotid endarterectomy by eversion technique: its safety and durability.
      • Winkler G.A.
      • Calligaro K.D.
      • Kolakowski S.
      • Doerr K.J.
      • McAffee-Bennett S.
      • Muller K.
      • et al.
      Comparison of intraoperative completion flowmeter versus duplex ultrasonography and contrast arteriography for carotid endarterectomy.
      • Wistrand J.
      • Mätzsch T.
      • Gonçalves I.
      • Riva L.
      • Dias N.V.
      Changing from conventional to eversion endarterectomy in carotid artery disease–a safe transition process in the short and long term.
      were OSs. A total of 49,500 CEA procedures were included, with 16,249 patients undergoing eCEA and 33,251 patients undergoing cCEA. Some studies included patch closure CEAs only
      • Demirel S.
      • Attigah N.
      • Bruijnen H.
      • Ringleb P.
      • Eckstein H.H.
      • Fraedrich G.
      • et al.
      SPACE Investigators
      Multicenter experience on eversion versus conventional carotid endarterectomy in symptomatic carotid artery stenosis: observations from the Stent-Protected Angioplasty Versus Carotid Endarterectomy (SPACE-1) trial.
      • Ben Ahmed S.
      • Daniel G.
      • Benezit M.
      • Bailly P.
      • Aublet-Cuvelier B.
      • Mulliez A.
      • et al.
      Does the technique of carotid endarterectomy determine postoperative hypertension?.
      • Ballotta E.
      • Da Giau G.
      • Saladini M.
      • Abbruzzese E.
      • Renon L.
      • Toniato A.
      Carotid endarterectomy with patch closure versus carotid eversion endarterectomy and reimplantation: a prospective randomized study.
      • Ballotta E.
      • Renon L.
      • Da Giau G.
      • Toniato A.
      • Baracchini C.
      • Abbruzzese E.
      • et al.
      A prospective randomized study on bilateral carotid endarterectomy: patching versus eversion.
      • Brothers T.E.
      Initial experience with eversion carotid endarterectomy: absence of a learning curve for the first 100 patients.
      • Crawford R.S.
      • Chung T.K.
      • Hodgman T.
      • Pedraza J.D.
      • Corey M.
      • Cambria R.P.
      Restenosis after eversion vs patch closure carotid endarterectomy.
      • Entz L.
      • Járányi Z.
      • Nemes A.
      Comparison of perioperative results obtained with carotid eversion endarterectomy and with conventional patch plasty.
      • Green R.M.
      • Greenberg R.
      • Illig K.
      • Shortell C.
      • Ouriel K.
      Eversion endarterectomy of the carotid artery: technical considerations and recurrent stenoses.
      • Littooy F.N.
      • Gagovic V.
      • Sandu C.
      • Mansour A.
      • Kang S.
      • Greisler H.P.
      Comparison of standard carotid endarterectomy with Dacron patch angioplasty versus eversion carotid endarterectomy during a 4-year period.
      • Peiper C.
      • Nowack J.
      • Ktenidis K.
      • Reifenhäuser W.
      • Keresztury G.
      • Horsch S.
      Eversion endarterectomy versus open thromboendarterectomy and patch plasty for the treatment of internal carotid artery stenosis.
      • Vanmaele R.G.
      • Van Schil P.E.
      • DeMaeseneer M.G.
      • Meese G.
      • Lehert P.
      • Van Look R.F.
      Division-endarterectomy-anastomosis of the internal carotid artery: a prospective randomized comparative study.
      • Winkler G.A.
      • Calligaro K.D.
      • Kolakowski S.
      • Doerr K.J.
      • McAffee-Bennett S.
      • Muller K.
      • et al.
      Comparison of intraoperative completion flowmeter versus duplex ultrasonography and contrast arteriography for carotid endarterectomy.
      or primary closure CEA only.
      • Kieny R.
      • Hirsch D.
      • Seiller C.
      • Thiranos J.C.
      • Petit H.
      Does carotid eversion endarterectomy and reimplantation reduce the risk of restenosis?.
      Others included both pCEA and dCEA,
      • Menyhei G.
      • Björck M.
      • Beiles B.
      • Halbakken E.
      • Jensen L.P.
      • Lees T.
      • et al.
      Outcome following carotid endarterectomy: lessons learned from a large international vascular registry.
      • Cao P.
      • Giordano G.
      • De Rango P.
      • Caporali S.
      • Lenti M.
      • Ricci S.
      • et al.
      Eversion versus conventional carotid endarterectomy: a prospective study.
      • Cao P.
      • Giordano G.
      • De Rango P.
      • Zannetti S.
      • Chiesa R.
      • Coppi G.
      • et al.
      A randomized study on eversion versus standard carotid endarterectomy: study design and preliminary results: the Everest Trial.
      • Economopoulos K.J.
      • Gentile A.T.
      • Berman S.S.
      Comparison of carotid endarterectomy using primary closure, patch closure, and eversion techniques.
      • Katras T.
      • Baltazar U.
      • Rush D.S.
      • Sutterfield W.C.
      • Harvill L.M.
      • Stanton Jr., P.E.
      Durability of eversion carotid endarterectomy: comparison with primary closure and carotid patch angioplasty.
      • Markovic D.M.
      • Davidovic L.B.
      • Cvetkovic D.D.
      • Maksimovic Z.V.
      • Markovic D.Z.
      • Jadranin D.B.
      Single-center prospective, randomized analysis of conventional and eversion carotid endarterectomy.
      • Shah D.M.
      • Darling 3rd, R.C.
      • Chang B.B.
      • Paty P.S.
      • Kreienberg P.B.
      • Lloyd W.E.
      • et al.
      Carotid endarterectomy by eversion technique: its safety and durability.
      • Wistrand J.
      • Mätzsch T.
      • Gonçalves I.
      • Riva L.
      • Dias N.V.
      Changing from conventional to eversion endarterectomy in carotid artery disease–a safe transition process in the short and long term.
      while some did not specify how the arteriotomy was closed.
      • Lee J.H.
      • Suh B.Y.
      Comparative results of conventional and eversion carotid endarterectomy.
      • Yasa H.
      • Akyuz M.
      • Yakut N.
      • Aslan O.
      • Akyuz D.
      • Ozcem B.
      • et al.
      Comparison of two surgical techniques for carotid endarterectomy: conventional and eversion.
      • Schneider J.R.
      • Helenowski I.B.
      • Jackson C.R.
      • Verta M.J.
      • Zamor K.C.
      • Patel N.H.
      • et al.
      Society for Vascular Surgery Vascular Quality Initiative and the Mid-America Vascular Study Group
      A comparison of results with eversion versus conventional carotid endarterectomy from the Vascular Quality Initiative and the Mid-America Vascular Study Group.
      • Radak D.
      • Radević B.
      • Sternić N.
      • Vucurević G.
      • Petrović B.
      • Ilijevski N.
      • et al.
      Single center experience on eversion versus standard carotid endarterectomy: a prospective non-randomized study.
      Finally some studies did not specifically differentiate outcomes between pCEA and dCEA.
      • Lee J.H.
      • Suh B.Y.
      Comparative results of conventional and eversion carotid endarterectomy.
      • Yasa H.
      • Akyuz M.
      • Yakut N.
      • Aslan O.
      • Akyuz D.
      • Ozcem B.
      • et al.
      Comparison of two surgical techniques for carotid endarterectomy: conventional and eversion.
      • Schneider J.R.
      • Helenowski I.B.
      • Jackson C.R.
      • Verta M.J.
      • Zamor K.C.
      • Patel N.H.
      • et al.
      Society for Vascular Surgery Vascular Quality Initiative and the Mid-America Vascular Study Group
      A comparison of results with eversion versus conventional carotid endarterectomy from the Vascular Quality Initiative and the Mid-America Vascular Study Group.
      • Cao P.
      • Giordano G.
      • De Rango P.
      • Caporali S.
      • Lenti M.
      • Ricci S.
      • et al.
      Eversion versus conventional carotid endarterectomy: a prospective study.
      • Cao P.
      • Giordano G.
      • De Rango P.
      • Zannetti S.
      • Chiesa R.
      • Coppi G.
      • et al.
      A randomized study on eversion versus standard carotid endarterectomy: study design and preliminary results: the Everest Trial.
      • Markovic D.M.
      • Davidovic L.B.
      • Cvetkovic D.D.
      • Maksimovic Z.V.
      • Markovic D.Z.
      • Jadranin D.B.
      Single-center prospective, randomized analysis of conventional and eversion carotid endarterectomy.
      • Radak D.
      • Radević B.
      • Sternić N.
      • Vucurević G.
      • Petrović B.
      • Ilijevski N.
      • et al.
      Single center experience on eversion versus standard carotid endarterectomy: a prospective non-randomized study.
      • Shah D.M.
      • Darling 3rd, R.C.
      • Chang B.B.
      • Paty P.S.
      • Kreienberg P.B.
      • Lloyd W.E.
      • et al.
      Carotid endarterectomy by eversion technique: its safety and durability.
      • Wistrand J.
      • Mätzsch T.
      • Gonçalves I.
      • Riva L.
      • Dias N.V.
      Changing from conventional to eversion endarterectomy in carotid artery disease–a safe transition process in the short and long term.
       An assessment of the methodological quality of the included studies using the Cochrane risk of bias assessment tool for the RCTs and the NOS for the OSs is presented in Table 2, Table 3, respectively.
      Table 2Assessment of the methodological quality of the included randomised controlled trials using the Cochrane risk of bias assessment tool.
      Reference (year)Random sequence generationAllocation concealmentBinding of participant/personnelBinding of outcome assessmentIncomplete outcome data
      Vanmaele et al
      • Vanmaele R.G.
      • Van Schil P.E.
      • DeMaeseneer M.G.
      • Meese G.
      • Lehert P.
      • Van Look R.F.
      Division-endarterectomy-anastomosis of the internal carotid artery: a prospective randomized comparative study.
      (1994)
      LowHighHighLowHigh
      Cao et al
      • Cao P.
      • Giordano G.
      • De Rango P.
      • Zannetti S.
      • Chiesa R.
      • Coppi G.
      • et al.
      A randomized study on eversion versus standard carotid endarterectomy: study design and preliminary results: the Everest Trial.
      (1998)
      LowHighHighLowLow
      Ballotta et al
      • Ballotta E.
      • Da Giau G.
      • Saladini M.
      • Abbruzzese E.
      • Renon L.
      • Toniato A.
      Carotid endarterectomy with patch closure versus carotid eversion endarterectomy and reimplantation: a prospective randomized study.
      (1999)
      LowHighHighLowLow
      Ballotta et al
      • Ballotta E.
      • Renon L.
      • Da Giau G.
      • Toniato A.
      • Baracchini C.
      • Abbruzzese E.
      • et al.
      A prospective randomized study on bilateral carotid endarterectomy: patching versus eversion.
      (2000)
      LowHighHighLowHigh
      Markovic et al
      • Markovic D.M.
      • Davidovic L.B.
      • Cvetkovic D.D.
      • Maksimovic Z.V.
      • Markovic D.Z.
      • Jadranin D.B.
      Single-center prospective, randomized analysis of conventional and eversion carotid endarterectomy.
      (2008)
      LowHighHighLowHigh
      Table 3Assessment of the methodological quality of the included observational studies using the Newcastle-Ottawa score.
      Study (year)Selection (maximum 4 stars)Comparability (maximum 2 stars)Outcome (maximum 3 stars)Total Newcastle-Ottawa score
      Kieny et al
      • Kieny R.
      • Hirsch D.
      • Seiller C.
      • Thiranos J.C.
      • Petit H.
      Does carotid eversion endarterectomy and reimplantation reduce the risk of restenosis?.
      (1993)
      2114
      Cao et al
      • Cao P.
      • Giordano G.
      • De Rango P.
      • Caporali S.
      • Lenti M.
      • Ricci S.
      • et al.
      Eversion versus conventional carotid endarterectomy: a prospective study.
      (1997)
      3216
      Entz et al
      • Entz L.
      • Járányi Z.
      • Nemes A.
      Comparison of perioperative results obtained with carotid eversion endarterectomy and with conventional patch plasty.
      (1997)
      2114
      Shah et al
      • Shah D.M.
      • Darling 3rd, R.C.
      • Chang B.B.
      • Paty P.S.
      • Kreienberg P.B.
      • Lloyd W.E.
      • et al.
      Carotid endarterectomy by eversion technique: its safety and durability.
      (1998)
      3227
      Economopoulos et al
      • Economopoulos K.J.
      • Gentile A.T.
      • Berman S.S.
      Comparison of carotid endarterectomy using primary closure, patch closure, and eversion techniques.
      (1999)
      3238
      Peiper et al
      • Peiper C.
      • Nowack J.
      • Ktenidis K.
      • Reifenhäuser W.
      • Keresztury G.
      • Horsch S.
      Eversion endarterectomy versus open thromboendarterectomy and patch plasty for the treatment of internal carotid artery stenosis.
      (1999)
      2114
      Radak et al
      • Radak D.
      • Radević B.
      • Sternić N.
      • Vucurević G.
      • Petrović B.
      • Ilijevski N.
      • et al.
      Single center experience on eversion versus standard carotid endarterectomy: a prospective non-randomized study.
      (2000)
      3227
      Green et al
      • Green R.M.
      • Greenberg R.
      • Illig K.
      • Shortell C.
      • Ouriel K.
      Eversion endarterectomy of the carotid artery: technical considerations and recurrent stenoses.
      (2000)
      3216
      Katras et al
      • Katras T.
      • Baltazar U.
      • Rush D.S.
      • Sutterfield W.C.
      • Harvill L.M.
      • Stanton Jr., P.E.
      Durability of eversion carotid endarterectomy: comparison with primary closure and carotid patch angioplasty.
      (2001)
      3227
      Littooy et al
      • Littooy F.N.
      • Gagovic V.
      • Sandu C.
      • Mansour A.
      • Kang S.
      • Greisler H.P.
      Comparison of standard carotid endarterectomy with Dacron patch angioplasty versus eversion carotid endarterectomy during a 4-year period.
      (2004)
      3126
      Brothers
      • Brothers T.E.
      Initial experience with eversion carotid endarterectomy: absence of a learning curve for the first 100 patients.
      (2005)
      3216
      Winkler et al
      • Winkler G.A.
      • Calligaro K.D.
      • Kolakowski S.
      • Doerr K.J.
      • McAffee-Bennett S.
      • Muller K.
      • et al.
      Comparison of intraoperative completion flowmeter versus duplex ultrasonography and contrast arteriography for carotid endarterectomy.
      (2006)
      2114
      Crawford et al
      • Crawford R.S.
      • Chung T.K.
      • Hodgman T.
      • Pedraza J.D.
      • Corey M.
      • Cambria R.P.
      Restenosis after eversion vs patch closure carotid endarterectomy.
      (2007)
      3238
      Wistrand et al
      • Wistrand J.
      • Mätzsch T.
      • Gonçalves I.
      • Riva L.
      • Dias N.V.
      Changing from conventional to eversion endarterectomy in carotid artery disease–a safe transition process in the short and long term.
      (2010)
      2226
      Menyhei et al
      • Menyhei G.
      • Björck M.
      • Beiles B.
      • Halbakken E.
      • Jensen L.P.
      • Lees T.
      • et al.
      Outcome following carotid endarterectomy: lessons learned from a large international vascular registry.
      (2011)
      4127
      Demirel et al
      • Demirel S.
      • Attigah N.
      • Bruijnen H.
      • Ringleb P.
      • Eckstein H.H.
      • Fraedrich G.
      • et al.
      SPACE Investigators
      Multicenter experience on eversion versus conventional carotid endarterectomy in symptomatic carotid artery stenosis: observations from the Stent-Protected Angioplasty Versus Carotid Endarterectomy (SPACE-1) trial.
      (2012)
      3216
      Lee and Suh
      • Lee J.H.
      • Suh B.Y.
      Comparative results of conventional and eversion carotid endarterectomy.
      (2014)
      3227
      Yasa et al
      • Yasa H.
      • Akyuz M.
      • Yakut N.
      • Aslan O.
      • Akyuz D.
      • Ozcem B.
      • et al.
      Comparison of two surgical techniques for carotid endarterectomy: conventional and eversion.
      (2014)
      3238
      Schneider et al
      • Schneider J.R.
      • Helenowski I.B.
      • Jackson C.R.
      • Verta M.J.
      • Zamor K.C.
      • Patel N.H.
      • et al.
      Society for Vascular Surgery Vascular Quality Initiative and the Mid-America Vascular Study Group
      A comparison of results with eversion versus conventional carotid endarterectomy from the Vascular Quality Initiative and the Mid-America Vascular Study Group.
      (2015)
      2114
      Ben Ahmed et al
      • Ben Ahmed S.
      • Daniel G.
      • Benezit M.
      • Bailly P.
      • Aublet-Cuvelier B.
      • Mulliez A.
      • et al.
      Does the technique of carotid endarterectomy determine postoperative hypertension?.
      (2015)
      2114

      RCT data only

      Table 4 summarises the main outcome analyses for when eCEA was compared with cCEA in RCT data only. Compared with cCEA, eCEA did not confer significant reductions in (i) 30 day stroke, (ii) 30 day death, (iii) 30 day death/stroke, (iv) 30 day MI, (v) 30 day death/stroke/MI, (vi) CNI, and (vii) neck haematoma. However, eCEA was associated with a significant reduction in late >50% restenosis, but not late ipsilateral stroke.
      Table 4Comparison of 30 day outcomes between eversion carotid endarterectomy (eCEA) vs. conventional carotid endarterectomy (cCEA)
      Conventional CEA included patients undergoing either primary closure or patch closure of the arteriotomy.
      using randomised controlled trial (RCT) data only.
      OutcomeTotal number of patientsWeighted proportionsOR (95% CI)pI2
      eCEAcCEAeCEAcCEA
      30 day stroke115712491.72%2.67%0.57 (0.31–1.04).0745.3%
      30 day death115712491.11%1.70%0.75 (0.34–1.70).5038.1%
      MI108911810.79%0.69%1.13 (0.39–3.25).810%
      30 day stroke/death115712492.66%4.32%0.37 (0.11–1.28).1265.9%
      30 day stroke/death/MI108911813.32%5.62%0.51 (0.18–1.46).2168.5%
      Recurrent stenosis9519391.98%4.54%0.40 (0.23–0.69).0010%
      Cranial nerve injury115712493.89%6.66%0.68 (0.45–1.01).0649.5%
      Neck haematoma95210533.88%6.19%0.69 (0.27–1.77).4466.7%
      MI = myocardial infarction.
      All significant p values are marked in bold.
      a Conventional CEA included patients undergoing either primary closure or patch closure of the arteriotomy.

      OS data only

      Table 5 summarises the main outcome analyses for when eCEA was compared with cCEA in OS data. Compared with cCEA, eCEA was associated with significant reductions in (i) 30 day ipsilateral stroke, (ii) 30 day death, (iii) 30 day death/stroke, (iv) 30 day death/stroke/MI, and (v) late >50% restenosis. There were no differences in 30 day rates of MI, CNI, or neck haematoma. A sensitivity analysis (using only OSs with a NOS >5) showed similar findings (Table 5).
      Table 5Comparison of outcomes between eversion CEA (eCEA) vs. conventional CEA (cCEA)
      Conventional CEA included patients undergoing either primary closure or patch closure of the arteriotomy.
      using data derived from observational studies only.
      OutcomeTotal meta-analysisSensitivity analysis (involving only those observational studies with NOS>5)
      Sensitivity analysis (which included only those observational studies with a NOS score >5). See Methods for details.
      Weighted proportionsTotal number of patientsOR (95% CI)pI2Weighted proportionsOR (95% CI)
      Sensitivity analysis (which included only those observational studies with a NOS score >5). See Methods for details.
      pI2
      eCEAcCEAeCEAcCEAeCEAcCEA
      30 day stroke1.18%2.14%11,06792030.58 (0.49–0.71)<.00011.5%1.56%3.03%0.62 (0.51–0.75)<.000138.6%
      30 day death0.83%1.49%11,06792030.46 (0.32–0.67)<.00010%0.83%1.30%0.57 (0.42–0.76).00020%
      MI0.91%0.89%527324451.01 (0.71–1.44).940%0.90%0.89%1.09 (0.61–1.94).780%
      30 day stroke/death2.26%4.32%11,06792030.52 (0.44–0.61)<.00010%2.36%4.21%0.59 (0.50–0.70)<.000139.6%
      30 day stroke/death/MI2.62%4.78%527324450.50 (0.38–0.67)<.00010%3.17%4.69%0.69 (0.53–0.90).00746.7%
      Recurrent stenosis2.34%4.68%543925690.49 (0.25–0.94).03277.9%2.77%4.31%0.63 (0.30–1.33).2278%
      Cranial nerve injury2.52%4.08%10,51385980.76 (0.37–1.56).4693%1.97%3.22%0.71 (0.29–1.78).4788.6%
      Neck haematoma2.70%2.04%511622821.25 (0.82–1.90).3149.2%3.80%2.56%1.34 (0.95–1.90).1027.6%
      NOS = Newcastle Ottawa scale; eCEA = eversion carotid endarterectomy; cCEA = conventional carotid endarterectomy; MI = myocardial infarction.
      All significant p values are marked in bold.
      a Conventional CEA included patients undergoing either primary closure or patch closure of the arteriotomy.
      b Sensitivity analysis (which included only those observational studies with a NOS score >5). See Methods for details.

      RCT and OS data combined

      Table 6 summarises the main outcome analyses for when eCEA was compared with cCEA in combined RCT and OS data. Compared with cCEA, eCEA was associated with significant reductions in (i) 30 day ipsilateral stroke, (ii) 30 day death, (iii) 30 day death/stroke, (iv) neck haematoma, and (v) late >50% restenosis. There were no differences in 30 day MI, 30 day death/stroke/MI, or CNI. A sensitivity analysis (using only OSs with a NOS >5) showed similar findings (Table 6).
      Table 6Comparison of outcomes between eversion CEA (eCEA) vs. conventional CEA (cCEA)
      Conventional CEA included patients undergoing either primary closure or patch closure of the arteriotomy.
      using combined data from randomised controlled trials and observational studies.
      OutcomeTotal meta-analysisSensitivity analysis (involving only those observational studies with NOS>5)
      Sensitivity analysis (which included only those observational studies with a NOS score >5). See Methods for details.
      Total number of patientsWeighted proportionsOR (95% CI)pI2Weighted proportionsOR (95% CI)
      Sensitivity analysis (which included only those observational studies with a NOS score >5). See Methods for details.
      pI2
      eCEAcCEAeCEAcCEAeCEAcCEA
      30 day stroke15,81728,6321.38%2.33%0.63 (0.46–0.86).00440.7%1.49%2.99%0.61 (0.51–0.86)<.000136.1%
      30 day death13,67211,8170.86%1.52%0.55 (0.43–0.72)<.00010%0.86%1.36%0.60 (0.45–0.79)<.00010.0%
      MI869020,6380.95%0.91%1.04 (0.75–1.45).820%0.89%0.84%1.09 (0.66–1.82).720%
      30 day stroke/death13,45211,4772.35%4.3%0.58 (0.50–0.67)<.000148.3%2.37%4.22%0.59 (0.42–0.82)<.000148.3%
      30 day stroke/death/MI632534833.19%4.74%0.68 (0.45–1.02).06550.9%2.27%5.01%0.33 (0.13–0.86).1732.5%
      Recurrent stenosis724642192.02%4.71%0.45 (0.26–0.78).00472.5%2.01%4.15%0.53 (0.29–0.95).03372.5%
      Cranial nerve injury14,47327,2472.77%4.82%0.69 (0.40–1.22).20590.4%2.31%4.29%0.63 (0.32–1.24).17886.3%
      Neck haematoma909121,0753.04%2.49%1.27 (1.01–1.58).03743.2%3.30%2.97%1.13 (0.86–1.49).03744.3%
      eCEA = eversion carotid endarterectomy; cCEA = conventional carotid endarterectomy; NOS = Newcastle Ottawa scale; MI = myocardial infarction.
      All significant p values are marked in bold.
      a Conventional CEA included patients undergoing either primary closure or patch closure of the arteriotomy.
      b Sensitivity analysis (which included only those observational studies with a NOS score >5). See Methods for details.

      Eversion CEA vs. patched CEA in RCTs and OSs

      Table 7 summarises the main outcome analyses for when eCEA was compared with outcomes in patients undergoing patched CEA in combined RCT and OS data. Compared with pCEA, eCEA was not associated with significant reductions in (i) 30 day death, (ii) 30 day stroke, (iii) 30 day MI, (iv) 30 day death/stroke, (v) CNI, (vi) neck haematoma, or (vii) late >50 restenosis. On the other hand, eCEA was associated with lower rates of 30 day stroke/death/MI, but because of small numbers, the statistical analysis did not produce reliable outcomes. eCEA was associated with lower rates of neck haematoma compared with pCEA. A sensitivity analysis (using only OSs with a NOS >5) showed similar findings (Table 7). Furthermore, eCEA was now associated with lower rates of CNI compared with pCEA.
      Table 7Comparison of 30 day outcomes between eversion CEA (eCEA) vs. patched CEA (pCEA) using data from randomised controlled trials and observational studies.
      OutcomeTotal meta-analysisSensitivity analysis (involving only those observational studies with NOS>5)
      Sensitivity analysis (which included only those observational studies with a NOS score >5). See Methods for details.
      Total number of patientsWeighted proportionsOR (95% CI)pI2Weighted proportionsOR (95% CI)
      Sensitivity analysis (which included only those observational studies with a NOS score >5). See Methods for details.
      pI2
      eCEApCEAeCEApCEAeCEApCEA
      30 day stroke756585841.38%1.93%0.71 (0.37–1.36).3058.7%1.41%1.85%0.81 (0.39–1.68).5748.3%
      30 day death778589240.86%1.12%0.64 (0.35–1.18).1568.7%0.73%0.77%0.95 (0.64–1.42).900%
      MI3713650.77%0.89%0.98 (0.17–5.69).980%0.77%0.89%0.98 (0.17–5.69).980%
      30 day stroke/death756585842.35%3.31%0.64 (0.35–1.18).1571.3%2.14%3.44%0.57 (0.28–1.18).1371.8%
      30 day stroke/death/MI3713653.19%5.42%
      The small number of patients with available data meant that calculations were deemed inaccurate.
      The small number of patients with available data meant that calculations were deemed inaccurate.
      The small number of patients with available data meant that calculations were deemed inaccurate.
      3.19%5.42%
      The small number of patients with available data meant that calculations were deemed inaccurate.
      The small number of patients with available data meant that calculations were deemed inaccurate.
      The small number of patients with available data meant that calculations were deemed inaccurate.
      Recurrent stenosis122012682.02%6.21%0.68 (0.24–1.95).4784.6%5.15%5.46%0.84 (0.27–2.66).7779.9%
      Cranial nerve injury622770724.82%7.18%0.50 (0.20–1.28).1589.9%2.32%6.19%0.37 (0.19–0.74).00591%
      Neck haematoma9329633.04%3.62%0.53 (0.30–0.95).030%4.78%10.25%0.43 (0.20–0.90).020.0%
      eCEA = eversion carotid endarterectomy; pCEA = patched carotid endarterectomy; NOS = Newcastle Ottawa scale; MI = myocardial infarction.
      a Sensitivity analysis (which included only those observational studies with a NOS score >5). See Methods for details.
      b The small number of patients with available data meant that calculations were deemed inaccurate.

      Discussion

      There are several methods of performing CEA, each with their own inherent advantages and disadvantages. In the first meta-analysis of RCT outcomes in 2001, there were no significant differences between cCEA and eCEA, except for a higher rate of late restenosis (>50%) following cCEA, although this disappeared when pCEA was compared with eCEA (i.e. having excluded dCEA patients).
      • Cao P.G.
      • de Rango P.
      • Zannetti S.
      • Giordano G.
      • Ricci S.
      • Celani M.G.
      Eversion versus conventional carotid endarterectomy for preventing stroke.
      By 2011, however, an updated meta-analysis (involving a much larger cohort of patients from mainly non-randomised studies) now suggested that eCEA conferred significant benefits relating to 30 day death, 30 day stroke, 30 day death/stroke, as well as lower rates of restenosis and late ipsilateral stroke. More importantly, these differences remained statistically significant when eCEA was compared with pCEA.
      • Antonopoulos C.N.
      • Kakisis J.D.
      • Sergentanis T.N.
      • Liapis C.D.
      Eversion versus conventional carotid endarterectomy: a meta-analysis of randomised and non-randomised studies.
      The current meta-analysis benefits from having three times the number of patients that were included in the 2011 meta-analysis.
      • Antonopoulos C.N.
      • Kakisis J.D.
      • Sergentanis T.N.
      • Liapis C.D.
      Eversion versus conventional carotid endarterectomy: a meta-analysis of randomised and non-randomised studies.
      If its findings corroborated the 2011 findings (especially if eCEA was superior to pCEA), this would constitute compelling evidence for preferentially performing eCEA over either dCEA or pCEA.
      As was observed with the 2011 meta-analysis,
      • Antonopoulos C.N.
      • Kakisis J.D.
      • Sergentanis T.N.
      • Liapis C.D.
      Eversion versus conventional carotid endarterectomy: a meta-analysis of randomised and non-randomised studies.
      combined RCT and OS data involving >49,000 patients in the 2017 updated meta-analysis suggested that eCEA conferred significant benefits over cCEA in terms of 30 day (reduced mortality, reduced death/stroke) and late outcomes (lower rates of restenosis). However, when the analysis was solely confined to RCTs, the findings were almost identical to those of the 2001 meta-analysis.
      • Cao P.G.
      • de Rango P.
      • Zannetti S.
      • Giordano G.
      • Ricci S.
      • Celani M.G.
      Eversion versus conventional carotid endarterectomy for preventing stroke.
      In short, eCEA conferred no significant benefit in terms of 30 day risk, although eCEA was associated with a significantly lower rate of late restenosis.
      • Cao P.G.
      • de Rango P.
      • Zannetti S.
      • Giordano G.
      • Ricci S.
      • Celani M.G.
      Eversion versus conventional carotid endarterectomy for preventing stroke.
      However, these findings are not unexpected as only one further RCT was added to the literature between 2002 and 2017.
      • Markovic D.M.
      • Davidovic L.B.
      • Cvetkovic D.D.
      • Maksimovic Z.V.
      • Markovic D.Z.
      • Jadranin D.B.
      Single-center prospective, randomized analysis of conventional and eversion carotid endarterectomy.
      So how should the findings of the 2017 meta-analysis influence contemporary clinical practice? Before concluding that eCEA is preferable to cCEA, the key message still appears to be the importance of stratifying for whether cCEA patients underwent primary arteriotomy closure or patch angioplasty. A meta-analysis of 10 RCTs (2157 patients), which compared routine patching versus routine primary closure, observed that routine patching was associated with significant reductions in 30 day ipsilateral stroke, compared with routine primary closure (patch 1.5% vs. 4.5% for primary closure; OR 0.2; 95% CI 0.1–0.6; p = .001), along with significant reductions in 30 day ICA thrombosis (0.5% pCEA vs. 3.1% for dCEA; OR 0.18; 95% CI 0.16–0.76; p = .0011).
      • Rerkasem K.
      • Rothwell P.M.
      Systematic review of randomized controlled trials of patch angioplasty versus primary closure and different types of patch materials during carotid endarterectomy.
      In addition, routine patching was associated with significantly lower rates of late restenosis (4.3% pCEA vs. 13.8% dCEA; OR 0.24; 95% CI 0.17–0.34; p < .01), as well as significant reductions in late ipsilateral stroke (1.6% pCEA vs. 4.8% dCEA; OR 0.32; 95% CI 0.16–0.63; p = .001).
      • Rerkasem K.
      • Rothwell P.M.
      Systematic review of randomized controlled trials of patch angioplasty versus primary closure and different types of patch materials during carotid endarterectomy.
      When data from RCTs and OSs were combined in the current meta-analysis and then stratified for whether the conventional CEA patient underwent either primary closure or patch angioplasty, all of the significant benefits apparently conferred by eCEA disappeared (Table 7). Compared with pCEA, eCEA was now not associated with significant reductions in (i) 30 day death, (ii) 30 day death/stroke, or (iii) late >50% restenosis. Accordingly, the data from the updated 2017 meta-analysis suggest that patients undergoing cCEA have very similar 30 day outcomes as well as late outcomes to patients undergoing eCEA, provided the arteriotomy is patched.
      The present meta-analysis does have limitations. Ideally, dCEA should be compared separately with pCEA and with eCEA. However, some studies did not differentiate outcomes between dCEA and pCEA patients.
      • Lee J.H.
      • Suh B.Y.
      Comparative results of conventional and eversion carotid endarterectomy.
      • Yasa H.
      • Akyuz M.
      • Yakut N.
      • Aslan O.
      • Akyuz D.
      • Ozcem B.
      • et al.
      Comparison of two surgical techniques for carotid endarterectomy: conventional and eversion.
      • Schneider J.R.
      • Helenowski I.B.
      • Jackson C.R.
      • Verta M.J.
      • Zamor K.C.
      • Patel N.H.
      • et al.
      Society for Vascular Surgery Vascular Quality Initiative and the Mid-America Vascular Study Group
      A comparison of results with eversion versus conventional carotid endarterectomy from the Vascular Quality Initiative and the Mid-America Vascular Study Group.
      • Cao P.
      • Giordano G.
      • De Rango P.
      • Caporali S.
      • Lenti M.
      • Ricci S.
      • et al.
      Eversion versus conventional carotid endarterectomy: a prospective study.
      • Cao P.
      • Giordano G.
      • De Rango P.
      • Zannetti S.
      • Chiesa R.
      • Coppi G.
      • et al.
      A randomized study on eversion versus standard carotid endarterectomy: study design and preliminary results: the Everest Trial.
      • Markovic D.M.
      • Davidovic L.B.
      • Cvetkovic D.D.
      • Maksimovic Z.V.
      • Markovic D.Z.
      • Jadranin D.B.
      Single-center prospective, randomized analysis of conventional and eversion carotid endarterectomy.
      • Radak D.
      • Radević B.
      • Sternić N.
      • Vucurević G.
      • Petrović B.
      • Ilijevski N.
      • et al.
      Single center experience on eversion versus standard carotid endarterectomy: a prospective non-randomized study.
      • Shah D.M.
      • Darling 3rd, R.C.
      • Chang B.B.
      • Paty P.S.
      • Kreienberg P.B.
      • Lloyd W.E.
      • et al.
      Carotid endarterectomy by eversion technique: its safety and durability.
      • Wistrand J.
      • Mätzsch T.
      • Gonçalves I.
      • Riva L.
      • Dias N.V.
      Changing from conventional to eversion endarterectomy in carotid artery disease–a safe transition process in the short and long term.
      In addition, in some of the studies that included pCEA only, there was inconsistency in the type of patch used (prosthetic vs. autologous vein).
      • Menyhei G.
      • Björck M.
      • Beiles B.
      • Halbakken E.
      • Jensen L.P.
      • Lees T.
      • et al.
      Outcome following carotid endarterectomy: lessons learned from a large international vascular registry.
      • Schneider J.R.
      • Helenowski I.B.
      • Jackson C.R.
      • Verta M.J.
      • Zamor K.C.
      • Patel N.H.
      • et al.
      Society for Vascular Surgery Vascular Quality Initiative and the Mid-America Vascular Study Group
      A comparison of results with eversion versus conventional carotid endarterectomy from the Vascular Quality Initiative and the Mid-America Vascular Study Group.
      The quality of some OSs was low (NOS <5).
      • Schneider J.R.
      • Helenowski I.B.
      • Jackson C.R.
      • Verta M.J.
      • Zamor K.C.
      • Patel N.H.
      • et al.
      Society for Vascular Surgery Vascular Quality Initiative and the Mid-America Vascular Study Group
      A comparison of results with eversion versus conventional carotid endarterectomy from the Vascular Quality Initiative and the Mid-America Vascular Study Group.
      • Ben Ahmed S.
      • Daniel G.
      • Benezit M.
      • Bailly P.
      • Aublet-Cuvelier B.
      • Mulliez A.
      • et al.
      Does the technique of carotid endarterectomy determine postoperative hypertension?.
      • Entz L.
      • Járányi Z.
      • Nemes A.
      Comparison of perioperative results obtained with carotid eversion endarterectomy and with conventional patch plasty.
      • Kieny R.
      • Hirsch D.
      • Seiller C.
      • Thiranos J.C.
      • Petit H.
      Does carotid eversion endarterectomy and reimplantation reduce the risk of restenosis?.
      • Peiper C.
      • Nowack J.
      • Ktenidis K.
      • Reifenhäuser W.
      • Keresztury G.
      • Horsch S.
      Eversion endarterectomy versus open thromboendarterectomy and patch plasty for the treatment of internal carotid artery stenosis.
      • Winkler G.A.
      • Calligaro K.D.
      • Kolakowski S.
      • Doerr K.J.
      • McAffee-Bennett S.
      • Muller K.
      • et al.
      Comparison of intraoperative completion flowmeter versus duplex ultrasonography and contrast arteriography for carotid endarterectomy.
      However, a sensitivity analysis (which excluded OSs with a NOS <5) did not observe any changes in the principle findings that had been reported for the cohort as a whole (30 day stroke, 30 day death, 30 day MI, 30 day stroke/death, 30 day stroke/death/MI, and late >50% restenosis). The percentage of symptomatic/asymptomatic patients and the time from the occurrence of the cerebrovascular event to CEA varied both within, as well as between studies. In addition, the majority of studies did not use a randomisation protocol for the selection of eCEA or pCEA. The potential for overlap between two studies from the same centre
      • Ballotta E.
      • Da Giau G.
      • Saladini M.
      • Abbruzzese E.
      • Renon L.
      • Toniato A.
      Carotid endarterectomy with patch closure versus carotid eversion endarterectomy and reimplantation: a prospective randomized study.
      • Ballotta E.
      • Renon L.
      • Da Giau G.
      • Toniato A.
      • Baracchini C.
      • Abbruzzese E.
      • et al.
      A prospective randomized study on bilateral carotid endarterectomy: patching versus eversion.
      is recognised. Cao et al published two consecutive series on outcomes after cCEA and eCEA, but there was no overlap in terms of patient recruitment.
      • Cao P.
      • Giordano G.
      • De Rango P.
      • Caporali S.
      • Lenti M.
      • Ricci S.
      • et al.
      Eversion versus conventional carotid endarterectomy: a prospective study.
      • Cao P.
      • Giordano G.
      • De Rango P.
      • Zannetti S.
      • Chiesa R.
      • Coppi G.
      • et al.
      A randomized study on eversion versus standard carotid endarterectomy: study design and preliminary results: the Everest Trial.
      By contrast, Ballotta published two sequential studies on eCEA and cCEA, where a small number of patients (n = 26) were common to both cohorts.
      • Ballotta E.
      • Da Giau G.
      • Saladini M.
      • Abbruzzese E.
      • Renon L.
      • Toniato A.
      Carotid endarterectomy with patch closure versus carotid eversion endarterectomy and reimplantation: a prospective randomized study.
      • Ballotta E.
      • Renon L.
      • Da Giau G.
      • Toniato A.
      • Baracchini C.
      • Abbruzzese E.
      • et al.
      A prospective randomized study on bilateral carotid endarterectomy: patching versus eversion.
      Finally, three studies
      • Katras T.
      • Baltazar U.
      • Rush D.S.
      • Sutterfield W.C.
      • Harvill L.M.
      • Stanton Jr., P.E.
      Durability of eversion carotid endarterectomy: comparison with primary closure and carotid patch angioplasty.
      • Shah D.M.
      • Darling 3rd, R.C.
      • Chang B.B.
      • Paty P.S.
      • Kreienberg P.B.
      • Lloyd W.E.
      • et al.
      Carotid endarterectomy by eversion technique: its safety and durability.
      • Vanmaele R.G.
      • Van Schil P.E.
      • DeMaeseneer M.G.
      • Meese G.
      • Lehert P.
      • Van Look R.F.
      Division-endarterectomy-anastomosis of the internal carotid artery: a prospective randomized comparative study.
      reported >60% (instead of >50%) restenosis rates, while another reported restenosis rates >80%.
      • Economopoulos K.J.
      • Gentile A.T.
      • Berman S.S.
      Comparison of carotid endarterectomy using primary closure, patch closure, and eversion techniques.
      The results of the present meta-analysis are in agreement with the 2017 European Society for Vascular Surgery (ESVS) guidelines for the management of atherosclerotic carotid and vertebral artery disease,
      • Naylor A.R.
      • Ricco J.B.
      • de Borst G.J.
      • Debus S.
      • de Haro J.
      • Halliday A.
      • et al.
      Editor's Choice - Management of Atherosclerotic Carotid and Vertebral Artery Disease: 2017 Clinical Practice Guidelines of the European Society for Vascular Surgery (ESVS).
      which suggested that eCEA provides equivalent outcomes to cCEA provided the arteriotomy is closed with a patch.
      In conclusion, this updated systematic review and meta-analysis reporting outcomes in nearly 50,000 CEA procedures has shown that eCEA was associated with similar outcomes to cCEA, provided the arteriotomy was closed with a patch.

      Conflict of interest

      None.

      Funding

      None.

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