Spyt, T; Abu-Omar, Y; Fynn, S; Thorpe, B; Stoneman, V

163 Pages·2017·18.07 MB·English

HEALTH TECHNOLOGY ASSESSMENT
VOLUME 22 ISSUE 19 APRIL 2018
ISSN 1366-5278
Amaze: a double-blind, multicentre randomised
controlled trial to investigate the clinical effectiveness
and cost-effectiveness of adding an ablation
device-based maze procedure as an adjunct to
routine cardiac surgery for patients with pre-existing
atrial fibrillation
Linda Sharples, Colin Everett, Jeshika Singh, Christine Mills, Tom Spyt,
Yasir Abu-Omar, Simon Fynn, Benjamin Thorpe, Victoria Stoneman,
Hester Goddard, Julia Fox-Rushby and Samer Nashef
DOI 10.3310/hta22190

Amaze: a double-blind, multicentre
randomised controlled trial to
investigate the clinical effectiveness and
cost-effectiveness of adding an ablation
device-based maze procedure as an adjunct
to routine cardiac surgery for patients
with pre-existing atrial fibrillation
Linda Sharples,1* Colin Everett,2 Jeshika Singh,3
Christine Mills,4 Tom Spyt,5 Yasir Abu-Omar,6
Simon Fynn,6 Benjamin Thorpe,2 Victoria Stoneman,4
Hester Goddard,4 Julia Fox-Rushby7 and Samer Nashef6
1Department of Medical Statistics, London School of Hygiene & Tropical
Medicine, London, UK
2Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, UK
3Health Economics Research Group (HERG), Brunel University London, London, UK
4Papworth Trials Unit Collaboration, Papworth Hospital, Cambridge, UK
5Department of Cardiac Surgery, Glenfield Hospital, Leicester, UK
6Department of Cardiology and Department of Cardiothoracic Surgery, Papworth
Hospital, Cambridge, UK
7Department of Population Science, King’s College London, London, UK
*Corresponding author
Declared competing interests of authors: SamerNashef receivedpersonal expenses from AtriCure, Inc.
(Amsterdam, the Netherlands) for contributing to educational courses for surgeonsinterested in learning
the mazeprocedure, independently of this study. AtriCure, Inc.is one of several manufacturers of atrial
fibrillation ablation devices, the technology of which was used in atrial fibrillation surgery in this study.
Published April 2018
DOI: 10.3310/hta22190

This reportshould be referenced as follows:
SharplesL, Everett C, Singh J, MillsC, SpytT, Abu-Omar Y,et al.Amaze:adouble-blind,
multicentrerandomisedcontrolledtrialtoinvestigatetheclinicaleffectivenessand
cost-effectivenessofaddinganablationdevice-basedmazeprocedureasanadjuncttoroutine
cardiacsurgeryforpatientswithpre-existingatrialfibrillation.HealthTechnolAssess2018;22(19).
HealthTechnology Assessment isindexed and abstracted in IndexMedicus/MEDLINE, Excerpta
Medica/EMBASE, ScienceCitation Index Expanded (SciSearch®) andCurrent Contents®/
Clinical Medicine.

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DOI:10.3310/hta22190 HEALTHTECHNOLOGYASSESSMENT2018 VOL.22 NO.19
Abstract
Amaze: a double-blind, multicentre randomised controlled
trial to investigate the clinical effectiveness and
cost-effectiveness of adding an ablation device-based maze
procedure as an adjunct to routine cardiac surgery for
patients with pre-existing atrial fibrillation
Linda Sharples,1* Colin Everett,2 Jeshika Singh,3 Christine Mills,4
Tom Spyt,5 Yasir Abu-Omar,6 Simon Fynn,6 Benjamin Thorpe,2
Victoria Stoneman,4 Hester Goddard,4 Julia Fox-Rushby7
and Samer Nashef6
1Department of Medical Statistics, London School ofHygiene &Tropical Medicine, London,UK
2Leeds Institute ofClinical Trials Research, University ofLeeds, Leeds, UK
3HealthEconomicsResearchGroup(HERG),BrunelUniversityLondon,London,UK
4Papworth Trials Unit Collaboration, Papworth Hospital, Cambridge, UK
5Department of Cardiac Surgery,Glenfield Hospital, Leicester, UK
6Department of Cardiology andDepartment of Cardiothoracic Surgery, Papworth Hospital,
Cambridge, UK
7Department of Population Science, King’s College London, London, UK
*Corresponding author [email protected]
Background: Atrial fibrillation (AF) can betreated using amaze procedureduring planned cardiac surgery,
but theeffect onclinical patient outcomes, and the cost-effectiveness compared withsurgery alone, are
uncertain.
Objectives: To determine whether or not themaze procedure issafe, improves clinical and patient
outcomes and iscost-effective for theNHS in patients with AF.
Design: Multicentre, Phase III, pragmatic, double-blind, parallel-arm randomised controlled trial. Patients
were randomised on a1:1 basis usingrandom permuted blocks, stratified for surgeon and planned
procedure.
Setting: Eleven acute NHS specialist cardiac surgical centres.
Participants: Patients aged ≥18 years, scheduledfor elective or in-house urgent cardiac surgery, witha
documented history (>3 months) of AF.
Interventions: Routine cardiac surgery withor without an adjunct mazeprocedure administered by anAF
ablation device.
Main outcome measures:The primary outcomes were return to sinus rhythm (SR) at 12 months and
quality-adjusted life-years (QALYs) over2 years after randomisation. Secondary outcomes included return
to SR at 2years, overall and stroke-free survival, drug use, quality of life (QoL), cost-effectiveness and
safety.
©Queen’sPrinterandControllerofHMSO2018.ThisworkwasproducedbySharplesetal.underthetermsofacommissioningcontractissuedbytheSecretaryofStatefor
HealthandSocialCare.Thisissuemaybefreelyreproducedforthepurposesofprivateresearchandstudyandextracts(orindeed,thefullreport)maybeincludedinprofessional vii
journalsprovidedthatsuitableacknowledgementismadeandthereproductionisnotassociatedwithanyformofadvertising.Applicationsforcommercialreproductionshould
beaddressedto:NIHRJournalsLibrary,NationalInstituteforHealthResearch,Evaluation,TrialsandStudiesCoordinatingCentre,AlphaHouse,UniversityofSouthamptonScience
Park,SouthamptonSO167NS,UK.
ABSTRACT
Results: Between25February2009and6March2014,352patientswererandomisedtothecontrol
(n=176)orexperimental(n=176)arms.Theoddsratio(OR)forreturntoSRat12monthswas2.06
[95%confidenceinterval(CI)1.20to3.54;p=0.0091].Themeandifference(95%CI)inQALYsat2years
betweenthetwotrialarms(maze/control)was–0.025(95%CI0.129to0.078;p=0.6319).TheORfor
SRat2yearswas3.24(95%CI1.76to5.96).Thenumberofpatientsrequiringanticoagulantdruguse
wassignificantlylowerinthemazearmfrom6monthsaftertheprocedure.Therewerenosignificant
differencesbetweenthetwoarmsinoperativeoroverallsurvival,stroke-freesurvival,needforcardioversion
orpermanentpacemakerimplants,NewYorkHeartAssociationFunctionalClassification(forheartfailure),
EuroQol-5Dimensions,three-levelversionscoreandShortFormquestionnaire-36itemsscoreatanytime
point.Sixtypercentofpatientsineachtrialarmhadaseriousadverseevent(p=1.000);mosteventswere
mild,but71patients(42.5%)inthemazearmand84patients(45.5%)inthecontrolarmhadmoderately
severeevents;31patients(18.6%)inthemazearmand38patients(20.5%)inthecontrolarmhadsevere
events.Themeanadditionalcostofthemazeprocedurewas£3533(95%CI£1321to£5746);themean
differenceinQALYswas–0.022(95%CI–0.1231to0.0791).Themazeprocedurewasnotcost-effective
at£30,000perQALYover2yearsinanyanalysis.Inasmallsubstudy,theactiveleftatrialejectionfraction
wassmallerthanthatofthecontrolpatients(meandifferenceof–8.03,95%CI–12.43to–3.62),but
withinthepredefinedclinicallyequivalentrange.
Limitations: Low recruitment, early release of trial summaries andintermittent resource-use collection may
have introduced bias and imprecise estimates.
Conclusions: Ablation can be practised safely in routine NHS cardiac surgical settings and increases return
to SRrates, but notsurvival or QoL upto 2years after surgery. Lower anticoagulant drug useand recovery
of leftatrial function support anticoagulant drug withdrawal provided that goodatrial function is
confirmed.
Further work: Continued follow-up and long-term clinical effectiveness and cost-effectiveness analysis.
Comparison of ablation methods.
Trial registration: Current Controlled Trials ISRCTN82731440.
Funding: This project was funded bythe NIHR Health Technology Assessment programme and willbe
published in full in HealthTechnology Assessment; Vol. 22,No. 19.See theNIHR Journals Library website
for further project information.
viii
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