Endovascular repair or open repair for ruptured abdominal aortic aneurysm

15 Pages·2016·2.1 MB·English

Endovascular repair or open repair for ruptured abdominal aortic
aneurysm: a Cochrane systematic review
Badger, S. A., Harkin, D. W., Blair, P. H., Ellis, P. K., Kee, F., & Forster, R. (2016). Endovascular repair or open
repair for ruptured abdominal aortic aneurysm: a Cochrane systematic review. BMJ Open, 6(2), e008391.
https://doi.org/10.1136/bmjopen-2015-008391
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Open Access Research
Endovascular repair or open repair for
ruptured abdominal aortic aneurysm:
a Cochrane systematic review
S A Badger,1 D W Harkin,2 P H Blair,2 P K Ellis,2 F Kee,3 R Forster4
Tocite:BadgerSA, ABSTRACT
Strengths and limitations of this study
HarkinDW,BlairPH,etal. Objectives:Emergencyendovascularaneurysmrepair
Endovascularrepairoropen
(eEVAR)mayimproveoutcomesforpatientswith ▪ This is the first study to do a meta-analysis of
repairforrupturedabdominal
aorticaneurysm:aCochrane rupturedabdominalaorticaneurysm(RAAA).The the three major randomised controlled trials
systematicreview.BMJOpen studyaimwastocomparetheoutcomesforeEVAR comparing endovascular and open repair of
2016;6:e008391. withconventionalopensurgicalrepairforthetreatment abdominalaorticaneurysms.
doi:10.1136/bmjopen-2015- ofRAAA. ▪ The major finding is that there is no difference
008391 Setting:Asystematicreviewofrelevantpublications seen between operative modalities for ruptured
wasperformed.Randomisedcontrolledtrials(RCTs) aneurysm repair in terms of morbidity or
▸ Prepublicationhistoryfor comparingeEVARwithopensurgicalrepairforRAAA mortality.
thispaperisavailableonline. wereincluded. ▪ Thequalityofthestudyisreducedbythelackof
Toviewthesefilesplease Participants:3RCTswereincluded,withatotalof completereportinginthetrials.
visitthejournalonline 761patientswithRAAA. ▪ Long-term outcome data would enhance the
(http://dx.doi.org/10.1136/ Interventions:Meta-analysiswasperformedwith resultsofthemeta-analysisandisstillawaited.
bmjopen-2015-008391). fixed-effectsmodelswithORsand 95%CIsfor ▪ Robust conclusions are difficult to draw due to
dichotomousdataandmeandifferenceswith95%CIs paucity of data, but one modality should not be
Received10April2015
forcontinuousdata. favouredoveranotherbasedoncurrentresearch.
Revised19August2015
Accepted21August2015 Primaryand secondaryoutcome measures:
Primaryoutcomewasshort-termmortality.Secondary
been recent decline in prevalence to about
outcomemeasuresincludedaneurysm-specificand
generalcomplicationrates,qualityoflifeandeconomic 2%. This is independent of participant selec-
analysis. tion criteria and reflects better cardiovascu-
Results:Overallriskofbiaswaslow.Therewasno lar risk profiling and management in the
differencebetweenthe2interventionson30-day(or overall population.1 2 Unfortunately, many
in-hospital)mortality,OR0.91(95%CI0.67to1.22; aneurysms first present as a rupture resulting
p=0.52).30-daycomplicationsincludedmyocardial indeath inthe majorityof those affected.
infarction,stroke,compositecardiaccomplications, ThehighmortalityratefromrupturedAAA
renalcomplications,severebowelischaemia,spinal
(RAAA) is well recognised. Clinicians have
cordischaemia,reoperation,amputationand
been reticent to apply scoring systems rigidly
respiratoryfailure.Reportingwasincomplete,andno
as to do so would condemn many to certain
robustconclusionwasdrawn.Forcomplication
death.3–5 Patients who undergo successful
outcomesthatdidincludeatleast2studiesinthe
open repair of RAAA enjoy a postoperative
meta-analysis,therewasnoclearevidencetosupport
adifferencebetweeneEVARandopenrepair.Longer quality of life similar to the ‘normal popula-
1MaterMisericordiae termoutcomesandcostperpatientwereevaluatedin tion’.6 7 The risk of aneurysm rupture is pro-
UniversityHospital,Dublin,
onlyasinglestudy,thusprecludingdefinite portional to aneurysm size, with aneurysms
Ireland
2BelfastVascularCentre, conclusions. measuring less than 5.4cm having an annual
RoyalVictoriaHospital, Conclusions:OutcomesbetweeneEVARandopen rupture rate of approximately 1% whereas
Belfast,UK repair,specifically30-daymortality,aresimilar. those greater than 7.0cm in diameter have
3CentreforPublicHealth, However,furtherhigh-qualitytrialsarerequired,asthe anannualrupturerateof32.5%.89Currently,
QueensUniversityBelfast, paucityofdatacurrentlylimitstheconclusions.
rupture leads to death in over 80% of those
Belfast,UK
4CentreforPopulationHealth affected, including 30–65% of those who
Sciences,Universityof receiveconventionalopensurgicalrepairand
Edinburgh,Edinburgh,UK is responsible for 2.1% of all deaths in men
BACKGROUND over 65years.8 10–12 These findings contrast
Correspondenceto Abdominal aortic aneurysm (AAA) affects with the significantly better outcome if con-
DWHarkin;
denis.harkin@belfasttrust. between 1.2% and 7.6% of the population ventional open surgical repair of the AAA is
hscni.net over 50years of age in the UK. There has plannedbeforerupturecanoccur.
BadgerSA,etal.BMJOpen2016;6:e008391.doi:10.1136/bmjopen-2015-008391 1
Open Access
Historically, open surgical repair was the only effective that open repair will remain the treatment for a large
treatment for AAA. This major operation carries signifi- proportion of patients whose AAA is unsuitable on ana-
cant morbidity and mortality, due to the combined tomical grounds for EVAR.16 19 20 In addition, long-term
effects of surgical exposure, haemorrhage and aortic results from the EVAR 1 trial should add caution, with
clamping with related lower torso ischaemia-reperfusion later ruptures in the EVAR group, and no long-term dif-
injury. However, with improved patient selection and ference in the all-cause mortality.21
perioperative care, some specialist centres are reporting Rupture of an AAA (RAAA) is a catastrophic event,
mortality rates of less than 2% and surgeons in non- withupto80%mortality.2223RAAAexposesthepatients
specialist units achieving mortality rates of 5–8%.8–10 to the combined injury of a period of haemorrhagic
However, in the past two decades, this treatment has shock and lower torso ischaemia followed by a reperfu-
been challenged by endovascular aneurysm repair sion injury on successful revascularisation. This ‘two hit’
(EVAR). Significant advancements in commercial stent mechanism of injury initiates a systemic inflammatory
design, delivery and implantation technique have made response syndrome, leading to a multiple organ dysfunc-
this avaluable alternative to open repair in selected suit- tion syndrome (MODS).24 MODS is the primary cause
able cases.13–15 Its use in elective cases has reduced early of 70% of such deaths and a contributory cause of the
postoperative morbidity and mortality.16 17 Its minimally remainder.25 26 The multiorgan failure, despite intensive
invasive nature allows it to be performed under regional care support, once established leads to death in over
or even local anaesthesia, rather than general anaesthe- 70% of cases.25 27 EVAR, especially under local anaesthe-
sia. This allows repair in patients with significant con- sia, reduces the physiological insult to the body as com-
comitant medical disease who may otherwise have been pared with conventional open surgical repair.28 29
considered unfit for surgery.10 18 Two recent large pro- Emergency EVAR (eEVAR) appears to offer a feasible
spective randomised controlled trials (RCTs) haveshown alternative to conventional open repair in selected
reduced early complications and mortality with patients.2930Emergencycaseswererepairedwithanaor-
EVAR.16 17 However, while elective endovascular repair touniiliac stent graft, contralateral occluder and fem-fem
clearly has a role, these trials reinforce the knowledge crossover in the initial years, due to increased speed of
Figure1 PRISMAflowchartof
literatureselection.TSC,Trials
SearchCo-ordinator.
2 BadgerSA,etal.BMJOpen2016;6:e008391.doi:10.1136/bmjopen-2015-008391
Open Access
achieving a seal and haemodynamic stability. However, electronic searches of MEDLINE, EMBASE, CINAHL,
the use of bifurcated stent graft is routine for ruptured AMED and through hand searching relevant journals.
AAA. Early reports have suggested a trend towards The full list of the databases, journals and conference
reduction in perioperative morbidity and mortality in proceedings which have been searched, as well as the
selected patients. Indeed evidence is emerging that the search strategies used are described in the Specialised
inflammatory response to RAAA repair and the asso- Register section of the Cochrane Peripheral Vascular
ciated organ dysfunction is attenuated by eEVAR com- Diseases Group module in The Cochrane Library.35 36
pared with open repair.31 32 References of relevant studies were reviewed for other
The purpose of this review was to assess the available pertinent publications.
evidence to support the use of eEVAR to treat RAAA.
The advantages and disadvantages of eEVAR for patients Datacollection and extraction
with RAAA was determined by the effect on short-term
Two authors (SAB and RB) independently reviewed the
mortality, major complication rates, aneurysm exclusion studies identified by the search for their relevance using
and late complications when compared with patients
the selection criteria. Disagreements were resolved
who have had conventional open repair of RAAA. The
through discussion. Two review authors (SAB and RB)
results of this review have been published as a Cochrane independently extracted data for each included study.
review,which was an update ofthe initial study.33 34
METHODS Table1 Thestringsearchperformedofthetermsinthe
Only prospective RCTs comparing eEVAR with conven- literature
tional open surgical repair were considered eligible for #1 MeSHdescriptor:[Ednovascular 6017
inclusion. Within the studies, all patients in whom a Procedures]explodealltrees
RAAA has been clinically diagnosed by CT, angiography, #2 MeSHdescriptor:[Stents]explodealltrees 3314
#3 MeSHdescriptor:[VascularSurgical 652
MR angiography or objective acute symptoms suggestive
Procedures]thistermonly
of impending rupture of the aneurysm to warrant inclu-
#4 Endovasc*:ti,ab,kw 941
sion. All types of endovascular devices were considered
#5 Endostent*:ti,ab,kw 1
in comparison with conventional open surgical treat-
#6 Endograft* 81
ment for patients consideredfit for surgery.
#7 EVRAR:ti,ab,kw 1
The primary outcome for the study was the short-term #8 (EVARorREVAR):ti,ab,kw 74
morality (30-day, or in-hospital mortality). Secondary #9 (Palmaz):ti,ab,kw 91
outcomes included: #10 *stent*orgraft* 54489
▸ Aneurysm exclusion, or further extravasation beyond #11 Palmaz:ti,ab,kw 91
the sac on follow-up imaging 30days after the #12 ViabahnorNitinolorHemobahnorIntracoil 207
procedure; orTantalumorpowerlinkorexcluderor
▸ Majorcomplications,suchasopenconversion,haemor- talentoraorfixorendologixoranaconda:ti,
ab,kw
rhage,myocardialinfarction,stroke,renalfailure(20%
#13 ZenithorDynalinkorHemobahnor 128
rise in creatinine levels), respiratory failure (require-
LuminexorMemothermorWallstent:ti,ab,
ment for postoperative mechanical ventilation), pneu-
kw
monia,bowelischaemia,lowerlimbischaemia;
#14 MeSHdescriptor:[BloodVesselProsthesis] 452
▸ Minor complications, such as catheter site haema- explodeallterms
toma, wound infection; #15 MeSHdescriptor:{BloodVesselProsthesis 508
▸ Long-term complications and mortality; reinterven- Implantation]thistermonly
tion rates for problems related to the RAAA or its #16 Endoprosthesis:ti,ab,kw 142
treatment will be sought where possible, as will cause #17 #1or#2or#3or#4or#5or#6or#7or#8 59170
of death, with or without reintervention, that is, or#9or#10or#11or#12or#13or#14or
#15or#16
device related;
▸ Qualityoflife (standardised questionnaires); #18 MeSHdescriptor:[Aneurysm,Ruptured] 201
▸ Economic analysis(cost per patient). explodeallterms
#19 MeSHdescriptor:[Aneurysm,Dissecting] 73
thistermonly
SEARCHMETHODS #20 (aneurysm*orabdom*orthoracoabdom*or 1195
thorac-abdom*oraort*)near(ruptur*or
For this update, the Cochrane Peripheral Vascular
tearorbleed*ortrauma)
Diseases Group Trials Search Co-ordinator (TSC)
#21 MeSHdescriptor:[Aorta]explodealltrees 317
searched the Specialised Register (last searched
andwithqualifier(s):[Surgery—SU]
February 2014) and the Cochrane Central Register of
#22 RAAA 12
Controlled Trials (CENTRAL) 2014, Issue 2, part of The
#23 #18or#19or#20or#21or#22 1545
Cochrane Library.35 The Specialised Register is main- #24 #17and#23inTrials 309
tained by the TSC and is constructed from weekly
BadgerSA,etal.BMJOpen2016;6:e008391.doi:10.1136/bmjopen-2015-008391 3
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Table2 ThedetailsoftheHinchliffestudy
Methods Studytype:single-centre,randomisedcontrolledtrial,openlabel,intention-to-treat
Studyaim:totestthehypothesisthatEVARcanreducetheperioperativemortalityof
rupturedAAA,comparedwithopenrepair
Country:England
Setting:hospital
Participants Numberrandomised:totaln=32(eEVARn=15;openrepairn=17)
Age(medianyears(IQR)):eEVAR=74years(68.8–79.5);openrepair=80years(73.8–83.8)
Gender(M/F):eEVAR=11/4;openrepair=13/4
Inclusioncriteria:allpatientsadmittedwithclinicallysuspectedorradiologicallyconfirmed
ruptureofaninfrarenalabdominalaorticaneurysmthat,intheopinionoftheduty
consultantvascularsurgeonwouldnormallybetreatedwithopenrepair
Exclusioncriteria:noendovascularteamavailable;fullselectionofemergencystentgrafts
notavailable;age<50years;inabilitytogiveverbalorwrittenconsent;unconsciouspatient;
allergytoradiologicalcontrast,stainlesssteelorpolyester;severecomorbiditythatwould
precludeintensivecaretreatmentfollowingopenrepair;previousendovascularAAArepair;
womenofchildbearingpotentialnottakingcontraception;pregnantandlactatingwomen
eEVARanatomicalsuitability(exclusioncriteria):absolutecontraindications:noevidenceon
aneurysmrupture,juxtarenalaneurysm,neckdiameter>32mm,externaliliacartery
diameter>6mm;relativecontraindications:proximalnecklength<10mm,excessive
thrombusintheproximalneck,commoniliacarterylength<25mm,heavilycalcifiediliac
arteries
Interventions eEVARdescription:thosewithadiagnosticCTweretransferreddirectlytooperating
theatre,andthosewithoutfirsthadaCTscantodetermineaorticmeasurement;performed
indedicatedvascularoperatingtheatreusingaSiremobil2000imageintensifier,withdigital
subtractionangiographyfacilities;mostpatientsheparinised;two-pieceaortouniiliacstent
graftmadewithGianturcostentswithuncoveredsuprarenalcomponent;occludingdevice
usedincontralateralcommoniliacartery;afterdeploymentofstentgraft,afemoro-femoral
crossovergraftwasperformed
Openrepairdescription:afterrandomisationtoopenrepair,patientsweretransferred
directlytotheoperatingtheatre,accordingtolocalpractice;performedtransperitoneally
eitherbymidlineortransverseincisions;aortaclampedbelowrenalarteries;patientsno
heparinised;inlaytechniquewasusedandgraftsweregelatin-coatedpolyester
Outcomes Perioperativemortality,definedas30-dayorin-hospital
Notes ‘PatientsweredeemedsuitableforEVARif,intheopinionoftheoperatingsurgeon,they
couldperformtherepair’;participantsrecruitedSeptember2002toDecember2004;five
surgeonsonunit,requiredthatsurgeonandteamavailablehadsufficientexpertisetooffer
EVAR,ifnot,conventionalopenrepairwasoffered;unstablepatientsthatmightbe
disadvantagedbydelayincurredbyCTscancould,atthesurgeon’sdiscretion,notbe
randomisedandtakendirectlyforopenrepair
Riskofbias
Bias Authors’ Supportforjudgement
judgement
Randomsequencegeneration Unclear ‘Randomisationwasthenperformedfromsealedopaqueenvelopeskeptinthe
(selectionbias risk AccidentandEmergencyDepartment’.Unclearhowrandomisationsequence
wasgenerated
Allocationconcealment Lowrisk ‘Randomisationwasthenperformedfromsealedopaqueenvelopeskeptinthe
(selectionbias) AccidentandEmergencyDepartment’
Blindingofparticipantsand Lowrisk Studywasunblinded,duetonatureofinterventionbutunlikelytoinfluence
personnel(performancebias); outcomes.‘Thesurgeonswereblindedtothedimensionsofpatient’saorta
alloutcomes untilrandomisationhadtakenplace’toavoidbias
Blindingofoutcome Lowrisk Notpossibletoblindteamregardingallocationgroup,butunlikelytoinfluence
assessment (detectionbias);all outcomemeasures
outcomes
Incompleteoutcomedata Lowrisk Allpatientsaccountedfor;crossoverpatientsaccountedfor;similardropout
(attritionbias);alloutcomes ratesandreasonsbetweentreatmentgroups
Selectivereporting(reporting Lowrisk Mostoftheprotocoloutlinedinthetext;allrelevantoutcomesreported;with
bias) theexceptionofmortality,outcomesarenotwelldescribedinthemethods
Otherbias Unclear Underpoweredstudy:32oftherequired100patientsrecruited
risk
AAA,abdominalaorticaneurysm;eEVAR,emergencyendovascularaneurysmrepair;F,female;M,male.
4 BadgerSA,etal.BMJOpen2016;6:e008391.doi:10.1136/bmjopen-2015-008391
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Table3 ThedetailsoftheAmsterdamAcuteAneurysmTrial(AJAX)study
Methods Studytype:multicentre,randomisedcontrolledtrial,intention-to-treat
Studyaim:compareEVARandopenrepairintreatingRAAAonmortalityand
severecomplications
Country:TheNetherlands
Setting:threelargehospitalvascularcentresinAmsterdam
Participants Numberrandomised:totaln=116(eEVARn=57;openrepairn=59)
Age(meanyears,95%CI):eEVAR=74.5(72.3to77.5);openrepair=74.5(72.2to
76.8)
Gender(M/F):eEVAR=49/8;openrepair=50/9
Inclusioncriteria:maleandfemalesover18years;clinicaldiagnosisofRAAA;
aneurysmaccompaniedbyacutehaemorrhageoutsideoftheaorticwallofCTA;
suitableforeEVARandopenrepair
Exclusioncriteria:extensionoftheaneurysmtojuxtarenalorsuprarenalaorta;
kidneytransplant;horseshoekidney;allergytointravenouscontrast;connective
tissuedisease;severehaemodynamicinstabilityprohibitingCT
eEVARanatomicalsuitabilityrequirements:suitableinfrarenalanchoringsegment,
minimumlengthoftheinfrarenalsegmentofatleast10–15mm,infrarenaldiameter
of20–32mm,noobstructingcalcifications,tortuosityofthrombosis,suitableiliac
anchoringsegment,ipsilateraliliacdiameterof8–18mm,contralateraliliacdiameter
of10–20mm,atleastoneiliacarteryshouldbeabletoaccommodateanendograft
CVDriskfactors(n(%)):diabetes(EVARn=2(4%),openrepairn=1(2%));
hypertension(EVARn=13(23%),openrepairn=10(17%));smoker(EVARn=23
(40%),openrepairn=20(34%));hyperlipidaemia(EVARn=13(23%),openrepair
n=19(32%));renaldisease(EVARn=1(2%),openrepairn=2(3%));pulmonary
disease(EVARn=7(12%),openrepairn=3(5%));carotiddisease(EVARn=16
(28%),openrepairn=10(17%));cardiacdisease(EVARn=16(28%),openrepair
n=14(24%))TypeofRAAA:infrarenal
Interventions eEVARdescription:aortouniiliacendograftandcontralateraliliacoccludingdevice,
followedbyafemoro-femoralcrossoverbypassgraft
Openrepairdescription:midlinelaparotomyandexclusionofruptureaneurysmby
eitherpolyestertubeorbifurcatedgraft;conductedundergeneralanaesthesia
Outcomes Compositedeathandseverecomplicationsat30daysafterintervention;long-term
mortalityrates(6monthsafterrandomisation);lengthofhospitalandICUstay;
durationofintubation/ventilation;useofbloodproducts;forEVAR,occurrenceof
endoleaks
Notes Studyperiod:April2004toFebruary2011;threemaintrialcentres,allother(seven)
regionalhospitalstransferredparticipantstooneofthetrialcentres
Riskofbias
Bias Authors’ Supportforjudgement
judgement
Randomsequencegeneration Lowrisk ‘Therandomizationsequencewasgeneratedbyanindependent
(selectionbias) clinicalresearchunitusingALEAsoftwareforrandomizationin
clinicaltrialswitha1:1allocationusingrandomblocksizesof4or
6,stratifiedforeachparticipatingcentre’.
Allocationconcealment (selectionbias) Lowrisk ‘Allocationwasconcealedusingsequentiallynumberedopaque
sealedenvelopes’.
Blindingofparticipantsandpersonnel Lowrisk Surgicalteamnotpossibletoblind,butunlikelytoinfluence
(performancebias);alloutcomes outcomes
Blindingofoutcomeassessment Lowrisk Doubledatabaseentry;endpointadjudicationcommitteeblinded;
(detectionbias);alloutcomes independentsafetycommitteeblinded
Incompleteoutcomedata(attrition Lowrisk AllpatientsaccountedforinCONSORTdiagram;bothtreatment
bias);alloutcomes groupshadsimilardropoutratesandreasons
Selectivereporting(reportingbias) Unclearrisk AlthoughallpredescribedoutcomeslistedintheReimerink
publicationarereported,qualityoflifeandcost-effectivenessas
describedinthestudyprotocol,werenotincluded,suggesting
furtherpublicationstoemerge
Otherbias Lowrisk None
CVD,cardiovasculardisease;eEVAR,emergencyendovascularaneurysmrepair;F,female;ICU,intensivecareunit;M,male;RAAA,
rupturedabdominalaorticaneurysm.
BadgerSA,etal.BMJOpen2016;6:e008391.doi:10.1136/bmjopen-2015-008391 5
Open Access
Table4 ThedetailsoftheImmediateManagementofthePatientwithRupture:OpenVersusEndovascular(IMPROVE)
study
Methods Studytype:multicentre,randomisedcontrolledtrial,openlabel,intention-to-treat
Studyaim:toassesswhetherEVARvsopenrepairreducesearlymortalityforpatientswith
suspectedRAAA
Country:UKandCanada
Setting:30hospitalvascularunitsandspecialistcentres
Participants Numberrandomised:totaln=613(eEVARn=316;openrepairn=297)
Age(meanyears(±SD)):eEVAR=76.7(7.4);openrepair=76.7(7.8)
Gender(M/F):eEVAR=246/70;openrepair=234/63
Inclusioncriteria:menandwomenovertheageof50years;clinicaldiagnosisofRAAAor
rupturedaortoiliacaneurysm,madebyaseniortrialhospitalclinician
Exclusioncriteria:previousaneurysmrepair;ruptureofanisolatedinternaliliacaneurysm,
aortocavaloraortoentericfistulae;recentanatomicalassessmentoftheaorta;connective
tissuedisorder;ifinterventionwasconsideredfutile
eEVARanatomicalsuitabilityrequirements:noabsoluterequirementswillbesetforthe
study,butproximalneckmorphologywithadiameterexceeding32mmoralengthlessthan
10mmmaybeconsideredunfavourable,andiliacarterydiametersshouldbeintherangeof
8–22mm
CVDriskfactors(n(%)):notgiven
TypeofRAAA:‘rupturedAAAorrupturedaortoiliacaneurysm’
Interventions eEVARdescription:endovascularsupracoeliacaorticballoonocclusionwillbeusedto
supportlessstablepatients;mostinterventionsperformedwithaortouniiliacgraft,butsome
patientsreceivedbifurcatedgrafts,withsubsequentfemoro-femoralcrossovergraftwith
contralateraliliacocclusion;controlofaortaachievedusinglocal/regionanaesthesia,with
generalanaesthesiausedlaterinprocedureifnecessaryOpenrepairdescription:CTscanis
optional;aneurysmsrepairedbycross-clampingtheproximalaortaandinsertingaprosthetic
inlaygraft;performedundergeneralanaesthesia
Outcomes 30-daymortality,24handin-hospitalmortality,costs,reinterventionsatprimaryadmission
timeandplaceofdischarge;cost-effectivenessandmortalityat12monthsareplannedfor
futurereporting
Notes ParticipantsrecruitedSeptember2009toJuly2013;flowdiagramshows623randomised,
but10wereexcludedafterDataMonitoringCommitteereviewedparticipants,613usedin
analysis;only275(87%)ofEVARand261(88%)ofopenrepairhadconfirmedRAAA
Riskofbias
Bias Authors’ Supportforjudgement
judgement
Randomsequencegeneration Lowrisk ‘Andindependentcontractorprovidedtelephonerandomisation,with
(selectionbias) computer-generatedassignationofpatientsina1:1ratio,usingvariableblock
sizeandstratifiedbycentre’.
Allocationconcealment Lowrisk ‘Andindependentcontractorprovidedtelephonerandomisation,withcomputer
(selectionbias) generatedassignationofpatients…’
Blindingofparticipantsand Lowrisk Surgicalteamnotpossibletoblind,butunlikelytoinfluenceoutcomes
personnel(performancebias);
alloutcomes
Blindingofoutcome Lowrisk Dataverificationperformedcentrallyatthetrialcorelaboratory,unclearif
assessment (detectionbias); blinding,butunlikelytoinfluenceoutcomes
alloutcomes
Incompleteoutcomedata Lowrisk Allpatientsaccountedfor,withbothtreatmentgroupshavingsimilardropout
(attritionbias);alloutcomes rates/reasoning
Selectivereporting(reporting Unclearrisk Allpredescribedoutcomesreportedon,butnotallappropriateoutcomes
bias) reportedyet,suggestingfurtherpublicationstoemerge
Otherbias Lowrisk None
CVD,cardiovasculardisease;eEVAR,emergencyendovascularaneurysmrepair;F,female;M,male;RAAA,rupturedabdominalaortic
aneurysm.
Details about the trial design, characteristics of partici- exclusion, major and minor short-term complications,
pants, diagnosis of RAAA, eEVAR and open repair pro- long-term all-cause mortality and long-term complica-
cedures were recorded. Data were collected on the tions, quality of life, and economic analysis. If data were
primary outcome short-term mortality (30-day or missing from publications of the included studies,
in-hospital) and secondary outcomes: aneurysm attempts weremade tocontact studyauthors.
6 BadgerSA,etal.BMJOpen2016;6:e008391.doi:10.1136/bmjopen-2015-008391
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Figure2 Short-termmortality
(30-dayorin-hospital)of
emergencyendovascular
aneurysmrepair(eEVAR)versus
openrepair.
Assessment of riskof bias in included studies Acute Aneurysm Trial (AJAX) and Hinchliffe trials only
Included studies were evaluated for quality, independ- used aortouniiliac devices, while the Immediate
ently by two review authors (SAB and RB), using The Management of the Patient with Rupture: Open Versus
Cochrane Collaboration’stool for assessing riskof bias.36 Endovascular (IMPROVE) used both methods, with a
This tool provides judgements made on the domains of greater proportion being aortobiiliac.38–48 However, due
sequence generation, allocation concealment methods, to a paucity of information, subgroup analysis was not
blinding, incomplete outcome data, selective outcome possibleatthistime.
reporting and other relevant biases. Evaluations of low
risk, unclear risk or high risk were given for each of the
Sensitivityanalysis
six domains for each included study. Any disagreements
Although all the participants in the IMPROVE trial had
betweenreviewauthorswereresolvedthroughdiscussion.
a clinical diagnoses of RAAA, on start of the interven-
tion, it was found that only 536 (87%) of the 613 rando-
Measuresof treatment effect mised participants had, in fact, a ruptured AAA.46 48 Of
Analysis was planned on an intention-to-treat basis, and
the remaining 77 participants, 22 had symptomatic non-
therefore all randomised patients from the included ruptured AAA, or other final diagnoses. Sensitivity ana-
studies were to be included in analysis. The outcomes
lyses were planned to evaluate the effects of this trial on
that are dichotomous in nature were to be compiled
the outcomes.
into meta-analysis and ORs with 95% CIs were to be cal-
culated. For continuous data, meta-analysis would
provide mean differenceswithSDs. RESULTS
A total of 18 new citations were identified in the search.
Assessment of heterogeneity Four were considered not relevant as they were reviews,
A test for heterogeneity examines the null hypothesis and two were added to the excluded studies.49 50 One
that all studies are evaluating the same effect. We study, Endovasculaire ou Chirurgie dans les Anevrysmes
obtained p values comparing the test statistic with a χ2 aorto-iliaques Rompus (ECAR), fits the inclusion criteria,
distribution. A measure (I2) that describes the percent- but is currently ongoing, with no published data at this
age of total variation across studies due to heterogeneity time.51–53 Ten citations, from three studies, were newly
rather than by chance was included. Avalue of 0% indi- included.38–48 Five prospective comparative studies were
cates no observed heterogeneity, and larger values show excluded.29 49 50 54 55 The flow of included and excluded
increasing heterogeneity.37 studiesisillustratedbymeansofaPRISMAdiagram(figure
1).Thesearchstringresultsarepresentedintable1.
Data synthesis The three included studies had a total of 761 partici-
Dataextractedindependentlybytworeviewauthors(SAB pants.38–48 All three studies were RCTs comparing
and RB) was compiled and entered into RevMan by one eEVAR to open surgery repair in patients with a clinical
author (RB). Comparisons of data using meta-analyses diagnosis of RAAA on outcomes that included mortality
were undertaken using fixed-effects models, unless the and complications. AJAX and IMPROVE aimed to evalu-
testforheterogeneityyieldedavalue>50%,inwhichcase ate longer term mortality and complications, but at the
arandom-effectsmodelwasimplemented. time of this review, there was no long-term data pub-
lished from the IMPROVE trial. Also, the IMPROVE trial
Subgroup analysis and investigation of heterogeneity evaluated cost-effectiveness by comparing cost-per-
Weplannedtoperformsubgroupanalysistoevaluatethe patient between the two trial arms. Currently none of
impact of patients treated with aortouniiliac devices and the included studies have evaluated aneurysm exclusion,
those treated with aortobiiliac devices. The Amsterdam minorcomplications or qualityof life.
Figure3 Myocardialinfarction
ofemergencyendovascular
aneurysmrepair(eEVAR)versus
openrepair.
BadgerSA,etal.BMJOpen2016;6:e008391.doi:10.1136/bmjopen-2015-008391 7
Open Access
Figure4 Strokecomplicationofemergencyendovascularaneurysmrepair(eEVAR)versusopenrepair.
AJAX and IMPROVE were both multicentre studies, Blinding(performance bias and detection bias)
with AJAX taking place in Amsterdam, the Netherlands, Owing to the nature of the intervention, it is not pos-
and IMPROVE in the UK, with one studysite in Canada. sible to blind the surgeons and difficult to blind patients
Hinchliffe et al was a single-centre trial within England. and the research team to the treatment allocation.
All included participants had a clinical diagnosis of However, we determined that a lack of blinding is
RAAA,butintheIMPROVEstudyonly536outofthe613 unlikely to influence the outcomes of interest, and all
(87%) randomised participants actually had RAAA, the three have been listed as low risk for performance and
remaining 77 had symptomatic non-ruptured AAA (22), detection bias. Attempts were made to reduce the riskof
noAAA(10),orasymptomaticAAAoranotherfinaldiag- bias by the study authors: in the AJAX study, an end
nosis (45). For the AJAX study, all randomised partici- point adjudication committee and independent safety
pantswereconsideredsuitableforbotheEVARandopen committee, both blinded to treatment allocation, were
repair,whichintheHinchliffeandIMPROVEstudiessuit- utilised. The Hinchliffe study kept surgeons blinded to
abilityforeEVARwasdeterminedafterrandomisation.In dimensions of the aorta until randomisation was com-
theHinchliffeandAJAXstudies,aortouniiliacgraftswere pleted, and the IMPROVE study utilised a trial core
used in the endovascular trial arm, while the IMPROVE laboratory tocentrally verifyoutcomes.
trialusedboththisand,morepredominately,aortobiiliac
grafts. The data derived from the three studies are out-
Incomplete outcome data (attrition bias) and selective
linedintables2–4withqualityofdatadescribed.
reporting (reporting bias)
Five studies were excluded from this review. Three
All three included studies adequately accounted for all
studies were prospective trials, treating patients present-
ing with RAAA with eEVAR.29 54 55 However, their com- participants, giving thorough explanation of all dropout
rates and reasons. All three studies were at a low risk of
parison to open repair was made through retrospective,
‘historical controls’ or with open repair cohorts. One attrition bias. Both the AJAX and IMPROVE trials are
lacking important outcome data specified in their proto-
study was a prospective comparison between eEVAR and
cols, which include quality of life and costs for both
open repair in patients with RAAA, but the study was
non-randomised.49 A final study was a non-randomised studies, and complications and long-term survival for the
studyof 55 consecutive patients presenting with RAAA.50 IMPROVE study. It is assumed that these outcomes will
be reported in future publications, but until that data
A portion of the participants in the study were collected
are reported, the two studies are at an unclear risk of
retrospectivelyand a portion prospectively.
reporting bias. The Hinchliffe study reported on all out-
comesspecified.
Allocation (selection bias)
Both the AJAX and IMPROVE studies adequately
reported random sequence generation, but the Otherpotential sources of bias
Hinchliffe study did not give a description of how their The AJAX and IMPROVE studies appear to be free of
sequence was produced, and is therefore at unclear risk. other sources of bias, but the Hinchliffe study could be
For allocation concealment, all three studies clearly at riskof bias due to an underpowered study population.
explained adequate concealment methods. In the publication, it was reported that the study
Figure5 Cardiaccomplication(moderateorsevere)ofemergencyendovascularaneurysmrepair(eEVAR)versusopenrepair.
8 BadgerSA,etal.BMJOpen2016;6:e008391.doi:10.1136/bmjopen-2015-008391
Open Access
Figure6 Renalcomplications(moderateorsevere)ofemergencyendovascularaneurysmrepair(eEVAR)versusopenrepair.
required 100 participants to be adequately powered, yet Renal complications (moderate or severe)
theyonly included 32 patients. The AJAX and Hinchliffe studies reported renal compli-
cations, and the random-effects model used to analyse
the association found no clear difference between the
EFFECTS OF INTERVENTIONS
interventions, OR 0.70 (95% CI 0.09 to 5.24; p=0.73;
Mortality (30-dayor in-hospital)
figure6).
All three studies were included in the meta-analysis for
mortality (30-day or in-hospital). The fixed-effects
Severe bowel ischaemia
model found no clear evidence to support a difference
Only a single study evaluated severe bowel ischaemia
in mortality between eEVAR and open repair, OR 0.93
(95% CI 0.69 to 1.25; p=0.63; figure 2). When the (AJAX), which had an OR of 0.39 (95% CI 0.07 to
2.11), but as only one study was included, no overall
IMPROVE study was removed for sensitivity analysis, due
association could be determined (figure7).
to randomisation of patients that did not have RAAA,
the OR moved closer to one and the CI became wider
Spinal cord ischaemia
as the IMPROVE study had a larger study population
Spinal cord ischaemia was also only evaluated in the
than the other two included studies, OR 0.98 (95% CI
AJAX study, which had only one event. With an OR of
0.49 to1.95; p=0.95).
3.16 and a 95% CI of 0.13 to 79.17, very little can cur-
Complications (30-day) rently be concluded regarding this outcome (figure 8).
Myocardial infarction
Reoperation
Only the Hinchliffe study reported myocardial infarc-
tion, but only one event was reported so the CI is very The occurrence of reoperation, specific to the aneurysm
wide, OR 3.62 (95% CI 0.14 to 95.78; figure 3). As only repair, was reported in two studies (AJAX and
one study was included for this outcome, no overall asso- Hinchliffe). The fixed-effects model did not find clear
ciation could be determined, and thewide CI makes any evidence to support a difference between the interven-
conclusion spurious. tions, OR 0.89 (95% CI 0.39 to 2.01; p=0.78), again with
a rather wide CI (figure9).
Stroke
Both the AJAX and Hinchliffe studies reported stroke Amputation
events, but with very few events, and opposing findings, The AJAX trial was the only study to evaluate amputa-
the fixed-effects model, with a non-significant OR has a tion, and with the few events, all in the open repair
very wide CI that is difficult to derive any meaningful intervention group, the OR of 0.14 (95% CI 0.01 to
conclusion from (OR 0.71, 95% CI 0.12 to 4.31; p=0.71; 2.78) had awide CI and no association to be concluded,
figure4). as onlya single study was included (figure10).
Cardiac complications (moderate or severe) Respiratory failure
Cardiac complications were evaluated in the AJAX and Respiratory failure was evaluated in the Hinchliffe study,
Hinchliffe studies. The fixed-effects meta-analysis found alone. With only a single event in the eEVAR arm, the
a non-significant OR, but again with awide CI (OR 1.12, CI was very wide, OR 3.62 (95% CI 0.14 to 95.78) with
95% CI 0.38 to 3.30; p=0.84; figure 5). no overall association (figure 11).
Figure7 Bowelischaemiaofemergencyendovascularaneurysmrepair(eEVAR)versusopenrepair.
BadgerSA,etal.BMJOpen2016;6:e008391.doi:10.1136/bmjopen-2015-008391 9