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Dontuseaspirinforprimarypreventionofcardiovasculardisease|TheBMJ

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Dontuseaspirinforprimarypreventionof
cardiovasculardisease
BMJ2010340doi:http://dx.doi.org/10.1136/bmj.c1805(Published21April2010)Citethisas:BMJ
2010340:c1805
HelenBarnett,associateeditor1,PeterBurrill,specialistpharmaceuticaladviserforpublichealth 2,Ike
Iheanacho,editor1
1

DrugandTherapeuticsBulletin,BMJGroup,LondonWC1H9JR

DerbyshireCountyPrimaryCareTrust,NHSDerbyshireCounty,ChesterfieldS417PF

Correspondenceto:HBarnetthbarnett@bmjgroup.com
Accepted15March2010
Allpatientscurrentlytakingaspirinforprimarypreventionshouldbereviewedindividuallytoreconsiderwhether
suchtreatmentisjustified

Theclinicalproblem
CardiovasculardiseaseaccountedforaroundtwomilliondeathsintheEuropeanUnionin2000.1Dailylow
doseaspirinisestablishedinthesecondarypreventionofcardiovasculardisease.1234Inprimary
prevention,however,useoflowdoseaspirinisunlicensedintheUnitedKingdom,andpublishedevidence
doesnotsupporttheassumptionthatthebenefitsclearlyoutweightheharms.Sotheroutinepracticeof
startingpatientsonsuchtreatmentforprimarypreventionofcardiovasculardiseaseshouldbeabandoned.

Theevidenceforchange
Whetherthebenefitsofaspirininpeoplewithnohistoryofcardiovasculardiseaseoutweightheriskshasbeen
doubted.25Thisispartlybecauselongterm,lowdoseaspirintherapysubstantiallyincreasesthelikelihoodof
gastrointestinalhaemorrhage.6Also,publishedevidencehasneverunequivocallysupportedtheuseofaspirin
inthissetting,andaccumulatingdatahavefurtherunderminedsuchpractice.
Ametaanalysisofsixrandomisedcontrolledtrials(involvingatotalof95000participants)investigatedaspirin
fortheprimarypreventionofcardiovasculardisease.5Aspirinusereducedseriousvasculareventsbyabout
0.07%peryear(0.51%peryearwithaspirinv0.57%peryearwithcontroltreatment,P=0.0001).Thiswasdue
mainlytoanabsolutereductionofabout0.05%inthelikelihoodofnonfatalmyocardialinfarction(0.18%per
yearv0.23%peryearwithcontroltreatment,P<0.0001numberneededtotreatperyeararound2000).
However,aspirinresultedinanabsoluteincreaseinmajorgastrointestinalorotherextracranialbleedingof
about0.03%peryear(0.10%peryearv0.07%peryear,P<0.0001numberneededtoharmperyeararound
3300).Ratesofallcausemortality,deathduetocoronaryheartdisease,andstrokedidnotdiffersignificantly
betweentheaspirinandthecontrolgroups.Theproportionalreductioninseriousvasculareventsdidnot
dependsignificantlyonage,sex,bloodpressure,historyofdiabetes,orpredictedriskofcoronaryheart
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Dontuseaspirinforprimarypreventionofcardiovasculardisease|TheBMJ

disease.
Othersystematicreviewsandarecentlypublishedrandomisedtrialsupportthesefindings.78910Inasex
specificmetaanalysisofthesixprimarypreventiontrialsincludedintheAntithromboticTrialistsCollaboration
metaanalysis,5aspirintreatmentforameanof6.4yearsresultedinanaverageabsolutebenefitofaround3
cardiovasculareventspreventedper1000womenand4cardiovasculareventspreventedper1000men.7
Thiswasoffsetbyanadditional2.5majorbleedingeventsper1000womenand3majorbleedingeventsper
1000men.Areviewthatassessedfiverandomisedcontrolledtrialsofantiplateletagentsforprimaryor
secondarypreventioninpeoplewithhypertensionfoundthataspirindidnotreducethelikelihoodofstrokeor
allcardiovasculareventscomparedwithplaceboinpatientswithraisedbloodpressureandnoprior
cardiovasculardisease.Overall,themagnitudeofbenefitwithaspirinwassimilartothemagnitudeofharm.8A
thirdreviewassessedsixrandomisedcontrolledtrialsofaspirinthatincludedpeoplewithdiabetesandnopre
existingcardiovasculardiseaseitfoundnoreductioninthelikelihoodofmajorcardiovasculareventsorall
causemortalitywithaspirinasprimarypreventioninpeoplewithdiabetes.9
TheAspirinforAsymptomaticAtherosclerosistrial10randomised3350peopleaged5075withoutclinically
evidentcardiovasculardisease,butwithananklebrachialindexof0.95orlessdetectedonscreening(arisk
factorforcardiovascularevents),toreceiveentericcoatedaspirin100mgdailyorplacebo.Atameanfollow
upof8.2years,aspirinwasnomoreeffectivethanplaceboatreducingtheprimaryendpointoffatalornon
fatalcoronaryevent,stroke,orrevascularisation.
Withaspirinforprimaryprevention,theoverallabsolutereductionindisablingorfatalcardiovascularevents
seemssmallandatleastpartiallyoffsetbyanincreaseinseriousintracranialandextracranialbleeds.11
Currentlyavailabletrialsdonotseemtojustifygeneralguidelinesadvocatingtheroutineuseofaspirinfor
primarypreventioninapparentlyhealthypeople,andthisconclusionholdsregardlessofsuchindividuals
gender,bloodpressure,orpredictedriskofcardiovasculardisease,orofwhethertheyhaveahistoryof
diabetes.11

Barrierstochange
Severalguidelinespublishedbetween2005and2008recommendedaspirinfortheprimarypreventionof
cardiovasculardiseaseinvariousgroupsofpatients,includingcertainpatientswithtype2diabetes,3412
thosewithacardiovasculardiseaseriskof20%ormoreover10years,34andthosewitha10yearriskof
cardiovasculardiseasemortalityover10%.1TheScottishIntercollegiateGuidelinesNetworksrecently
publishedguidelineonmanagementofdiabetesstatesthatlowdoseaspirinisnotrecommendedforprimary
preventionofvasculardiseaseinpatientswithdiabetes.13However,theBritishHypertensionSocietyhas
recentlyreaffirmeditsguidancepromotingaspirinforprimaryprevention.14Theseguidelines,coupledwiththe
acceptancethatlowdoseaspirinisusefulforsecondaryprevention,mayhaveledtowidespreadprescribingof
aspirinforprimaryprevention,aswellasoverthecounterpurchasesofthedrugforselfmedication.Itisalso
worthnotingthatriskfactorsthatpredictvasculareventsalsopredicthaemorrhagicevents,5sopatientswho
willbenefitfromaspirincanbeidentifiedonthebasisofriskscoresonlyiftheyhavealreadyhadavascular
event.

Howshouldwechangeourpractice?
Lowdoseaspirinshouldnotberoutinelyusedforprimarypreventionofcardiovasculardisease.Current
evidencehasnotidentifiedaworthwhilenetbenefitfromsuchtreatment,eveninspecificsubgroupssuchas
patientswithraisedbloodpressureordiabetes.Furthermore,suchtreatmentisassociatedwithapotentialrisk
ofseriousbleeds.Allthosecurrentlytakingaspirinforprimarypreventionshouldbereviewedindividually,and
thedecisiontostoporcontinuetreatmentshouldbemadewiththesepatientsafterfullyinformingthemofthe
availableevidence.
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Searchmethods
WesearchedMedlineandtheCochraneLibrarytoidentifypublishedrandomisedcontrolledtrialsand
systematicreviewsthatassessedthesafetyandeffectivenessoforalaspirinfortheprimarypreventionof
cardiovasculardisease.Wealsoconsultedwidelyamongspecialistsandgeneralists,aswellasdrug
companies,toidentifyrelevantpublishedevidence.

Keypoints
Noevidenceexistsofworthwhilebenefit,andevidenceofaneffectonmortalityislacking,withaspirin
prophylaxisforprimarypreventionofcardiovasculardisease,eveninpeoplewithriskfactorssuchasraised
bloodpressureordiabetesmellitus
Aspirinisassociatedwithariskofseriousbleeds
AspirinisnotlicensedforprimarypreventionintheUnitedKingdom.Donotroutinelystartlowdoseaspirinfor
theprimarypreventionofcardiovasculardiseasereviewpatientscurrentlyreceivingtreatmentindividually,and
involvetheminthedecisionaboutwhethertostoptreatment

Notes
Citethisas:BMJ2010340:c1805

Footnotes
ChangePageaimstoalertclinicianstotheimmediateneedforachangeinpracticetomakeitconsistent
withcurrentevidence.Wewelcomesuggestionsforfuturearticles(changepage@bmj.com).
Contributors:PBsuggestedthereviewtopic.PBconductedtheinitialliteraturereview,whichwas
repeatedforverificationbyHB.HBandPBpreparedthefirstdraftofthepaper,whichwasrevisedbyII
andPB.IIisguarantor.
Competinginterests:Nonedeclared.
Provenanceandpeerreview:Commissionedexternallypeerreviewed.

References
1.FourthJointTaskforceoftheEuropeanSocietyofCardiologyandothersocietiesoncardiovasculardiseaseprevention
inclinicalpractice(constitutedbyrepresentativesofninesocietiesandbyinvitedexperts).Europeanguidelineson
cardiovasculardiseasepreventioninclinicalpractice:fulltext.EurJCardioPrevRehab200714:S1113.
2.AntithromboticTrialistsCollaboration.Collaborativemetaanalysisofrandomisedtrialsofantiplatelettherapyfor
preventionofdeath,myocardialinfarction,andstrokeinhighriskpatients.BMJ2002324:7186.
3.ScottishIntercollegiateGuidelinesNetwork.Riskestimationandthepreventionofcardiovasculardisease:anational
clinicalguideline.2007.www.sign.ac.uk/pdf/sign97.pdf
4.BritishCardiacSociety,BritishHypertensionSociety,DiabetesUK,HEARTUK,PrimaryCareCardiovascularSociety,
StrokeAssociation.JBS2:JointBritishSocietiesguidelinesonpreventionofcardiovasculardiseaseinclinical
practice.Heart 200591:v152.
5.AntithromboticTrialistsCollaboration.Aspirinintheprimaryandsecondarypreventionofvasculardisease:
collaborativemetaanalysisofindividualparticipantdatafromrandomisedtrials.Lancet 2009373:184960.
6.DerryS,LokeYK.Riskofgastrointestinalhaemorrhagewithlongtermuseofaspirin:metaanalyis.
BMJ2000321:11837.
7.BergerJS,RoncaglioniMC,AvanziniF,PangrazziI,TognoniG,BrownDL.Aspirinfortheprimarypreventionof
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Dontuseaspirinforprimarypreventionofcardiovasculardisease|TheBMJ

cardiovasculareventsinwomenandmen:asexspecificmetaanalysisofrandomizedcontrolledtrials.
JAMA2006295:30613.
8.LipGYH,FelmedenDC.Antiplateletagentsandanticoagulantsforhypertension.CochraneDatabaseofSystematic
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cardiovasculareventsinpeoplewithdiabetes:metaanalysisofrandomisedcontrolledtrials.BMJ2009339:b4531.
10.AspirinforAsymptomaticAtherosclerosisTrialists.Aspirinforpreventionofcardiovasculareventsinageneral
populationscreenedforalowanklebrachialindex:arandomizedcontrolledtrial.JAMA2010303:8418.
11.Aspirinforprimarypreventionofcardiovasculardisease?DrugTherBull 200947:1225.
12.NationalCollaboratingCentreforChronicConditions.Type2diabetes:nationalclinicalguidelineformanagementin
primaryandsecondarycare(update).2008.www.nice.org.uk/nicemedia/pdf/CG66FullGuideline0509.pdf
13.ScottishIntercollegiateGuidelinesNetwork.Managementofdiabetes:anationalclinicalguideline.March2010.
http://www.sign.ac.uk/pdf/sign116.pdf
14.SeverPS,BHSworkingparty.Aspirinandprimaryprevention:BHSreaffirmsitsguidance.BMJ 2010340:c1183.

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