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Bond UniversityResearch Repository
Patient preferences for cardiovascular preventive medicationAlbarqouni, Loai; Doust, Jenny; Glasziou, Paul
Published in:Heart
DOI:10.1136/heartjnl-2017-311244
Published: 01/10/2017
Document Version:Peer reviewed version
Link to publication in Bond University research repository.
Recommended citation(APA):Albarqouni, L., Doust, J., & Glasziou, P. (2017). Patient preferences for cardiovascular preventive medication: Asystematic review. Heart, 103(20), 1578-1586. https://doi.org/10.1136/heartjnl-2017-311244
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Download date: 10 Jul 2020
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Patient preferences for cardiovascular preventive medication: a systematic review
Loai Albarqouni1, Jenny Doust1, Paul Glasziou1
1 Centre for Research in Evidence-Based Practice (CREBP), Bond University, QLD 4226, Australia
Loai Albarqouni: MD, MSc, PhD candidate; Jenny Doust: FRACGP, PhD, GP, and Professor of clinical epidemiology; Paul Glasziou: FRACGP, PhD, Director, and Professor of Evidence-Based Medicine
Corresponding author:
Loai Albarqouni, MD, MSc Centre for Research in Evidence-Based Practice (CREBP) Faculty of Health Sciences and Medicine Bond University QLD, Australia 4229 Email: [email protected] Phone: +61(0)457699656
Manuscript word count: 3172 Abstract word count: 244 Number of tables and figures: 1 Table and 5 Figures Number of references: 50 Supplement: 1 Figure and 2 Tables
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Abstract
Objective:Tosystematicallyreviewcurrentevidenceregardingtheminimumacceptablerisk
reductionofacardiovasculareventwhichpatientsfeelwouldjustifydailyintakeofa
preventivemedication.
Methods:WeusedtheWebofSciencetotracktheforwardandbackwardscitationsofasetof
fivekeyarticlesuntil15November2016.Studieswereeligibleiftheyquantitativelyassessed
theminimumacceptablebenefit-inabsolutevalues-ofacardiovasculardiseasepreventive
medicationamongasampleofthegeneralpopulation,andrequiredparticipantstochooseif
theywouldconsidertakingthemedication.
Results:Of253studiesscreened,weincluded22,involvingatotalof17,751participants:6
studiedProlongationofLife(POL),12AbsoluteRiskReduction(ARR),and14studiedNumber
NeededtoTreat(NNT)asmeasuresofriskreductioncommunicatedtothepatients.Instudies
framedusingPOL,39-54%(average48%)ofparticipantswouldconsidertakingamedicationif
itprolongedlife<8months,and56-73%(average64%)≥8months.Instudiesframedusing
ARR,42-72%(average54%)ofparticipantswouldconsidertakingamedicationthatreduces
their5-yearCVriskby<3%,and50-89%(average77%)≥3%.Instudiesframedusing5-year
NNT,31-81%(average60%)ofparticipantswouldconsidertakingamedicationwithaNNTof>
30,and46-87%(average71%)£30.
Conclusions:Manypatientsrequireasubstantialrisk-reductionbeforetheyconsidertakinga
dailymedicationworthwhile,evenwhenthemedicationisdescribedasbeingside-effectfree
andcostless.
Keywords:CardiovascularDiseases,Communication,Decision-making,RiskAssessment,GuidelineAbbreviation:CVDCardiovascularDisease;ARRAbsoluteRiskReduction;NNTNumberNeededtoTreat;POL
ProlongationofLife
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Introduction
Cardiovasculardisease(CVD)istheleadingcauseofprematuredeathandreduceddisability
adjustedlife-yearsworldwide12.Thus,CVDprevention-whichmayrequiretheinitiationof
lifelongmedicationaimingatmodifyingspecificriskfactorsoffutureadverseevents3-has
been,andwillcontinuetobe,apublichealthpriority.
ClinicalPracticeGuidelines(CPGs)weredevelopedtoassistpractitionersandpatientsintheir
decisionsaboutappropriatehealthcareinterventions.However,diseasepreventiveguidelines
faceacrucialchallenge:individualsatriskoftenfeelhealthyandmightperceivemedicationsas
unnecessary,particularlythosehavinguncertainbenefitsand/orunpleasantsideeffects.This
challengecanleadtodisagreementbetweenhowguidelinespanelandpatientsvaluethe
benefitsandharmsofpreventivemedications4.Forinstance,whileguidelinespanelsmay
assumethatthebenefitsofapreventiveinterventionoutweighanypotentialharm,individual
patientsmaynotagreewiththeirtrade-off.Whenthereisuncertaintyinthetrade-off
betweenbenefitsandharmsofpreventiveinterventions5-7,incorporationofpatients’
preferencesisappropriateandimportant8.Accordingly,patientsmaydecidewhethertoaccept
orrejectsuchaninterventionbasedonweighingtheharms,cost,andinconvenienceoftaking
lifelongmedicationagainstthepotentiallong-termbenefits910.
Despitethegrowingacknowledgementoftheimportanceofpatientandpublicinvolvementin
thedevelopmentofCPGs,currentCPGsfocusprimarilyonthemedicationeffectivenessand
oftenfailtohighlightuncertaintyandreconcilepatientspreferencesandvalueswiththe
guidelinerecommendations11.Inaddition,CPGs’recommendationsareoftenusedasa
measureofthequalityofcareprovidedbycliniciansandorganisations1213.
Forinstance,themostrecentupdateoftheUSandUKCVDriskassessmentandprevention
guidelineshaverecommendedtheuseofstatinsamongpeoplepreviouslyconsideredatlow
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riskofcardiovasculardisease,settingthethresholdtocommencestatinsatariskofaCVD
eventin10yearsof7.5%1415.However,thisthresholdreflectsavaluejudgmentaboutthe
balanceofpotentialharmsandbenefitsoftakingstatins,whichsomepatientsmaynotfindit
justifiablefortakingstatins.
Therefore,thepurposeofthissystematicreviewwastosummarisecurrentevidenceregarding
theminimumacceptableriskreductionofacardiovasculareventwhichpatientsfeelwould
justifytheirtakingdailypreventivemedication.Thisinformationishelpfulbothforpatients,to
activelyparticipateinthedecision-makingprocess16,andguidelinespanelstobeinformedof
thebestevidenceregardingthepatientsvaluesandpreferencesinmakingtrade-offsbetween
desirableandundesirableconsequencesofsuchanintervention17.
Methods
Aprotocolforthissystematicreviewwasdevelopedinadvance(availablefromtheauthorson
request).
InformationSourcesandSearchMethods
Wedeveloped,withthehelpofamedicallibrarianexperiencedinsystematicreviews,asearch
strategyusingamethodofforwardandbackwardscitationanalysis.WeusedWebofScience
databasetotracktheforwardandbackwardscitationsofasetof5keyarticlesuntil15-
November-2016.Theindexarticlesforourcitationanalysiswerearelevantsystematicreview18
andfourotherarticlesidentifiedasimportantinthisarea9101920.Searchingcontinued
backwardandforwarduntilnofurtherrelevantstudiesarefound.Citationanalysiscanevade
thetime-consumingandthecomplexnatureofthestandardsearchstrategies,inareaswhere
indexingisunlikelytoretrieverelevantarticleswithanacceptableaccuracyrate21-23.
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EligibilityCriteria
Allpublishedquantitativeprimarystudieswereeligible,irrespectiveofthestudydesign.We
includedstudiesinvolvingadultparticipantswhomadeadecisionaboutacardiovascular
preventivemedicationwhetherinareal-life(actual)orahypothetical(analogous)scenario.
Studieswereeligibleiftheyassessedtheminimumacceptablebenefit(CVD-risk-reduction)ofa
CVDpreventivemedicationamongasampleofthegeneralpopulation,andprovideda
quantitativeestimateoftheriskreduction(inabsolutevalues)requiredbypatientstomake
dailymedicationworthwhile.Absoluteriskreductionestimatescouldbepresentedinthe
formatofProlongation-of-Life(POL),Absolute-Risk-Reduction(ARR)orNumber-Needed-to-
Treat(NNT).Studiesthatprovidedadescriptiveorqualitativeestimateofriskreductionora
quantitativeestimateofrelative-risk-reduction(withoutbaseline-risk)wereexcluded.
SelectionofStudies
Twoauthorsindependentlyscreenedforeligibilitythetitlesandabstractsofidentifiedarticles.
Weretrievedthefull-textofstudiesthatpotentiallymettheeligibilitycriteria.Fromthefull-
texts,twoauthorsindependentlyassessedstudyeligibility.Whenmorethanonepublicationof
thesamestudyexisted,thepublicationwiththemostcompletedatawasincluded.We
resolvedanydisagreementbydiscussion.Reasonsforexclusionofstudiesweredocumented.
DataExtraction
Twoauthorsindependentlyabstracteddata,usingastandardiseddataextractionform.The
abstracteddataincluded:(1)General:title,authors,country,languageandyearofpublication,
duplicatepublications,sponsoring;(2)Participants:samplesize,baselinecharacteristics,and
studysetting;(3)Scenario:Hypothetical/Real,typeofriskpresentationformat(POL,ARRor
NNT),methodforelicitingpatientspreferences(e.g.discretechoice),medication
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characteristics(sideeffects,cost,burden)andthetargetadverseevent(mortalityor
morbidity).
AssessmentofthemethodologicalqualityandRiskofBias
Includedstudieswereindependentlyassessedbytwoauthorsusingamodifiedversionofthe
riskofbiasinprevalencestudiesassessmenttool24,whichincludesthefollowingitems:
representation,selection,responserate,datacollection.Weassessedtheadequacyofeach
item:'low',‘unclearor‘high’riskofbias.
DataSynthesis
Foreachincludedstudy,weextractedorcalculatedtheaverage5-yearARRorNNTorPOL
requiredbytheparticipantstocommenceaCVDpreventivemedication.Wereportedthe
ranges(andsample-size-weightedaverages)of5-yearARRorNNTorPOLacrossincluded
studies.Ameta-analysiswasnotpossibleduetotheheterogeneityinstudies’methodsand
outcomes.
Results
Wescreened341studies(afterremovalofduplicates),ofwhich238wereclassedasineligible
basedontitlesorabstracts.Oftheremaining103full-texts,22studieswithatotalof17751
participantswereincluded(Figure1).
Studypublicationdatesrangedfrom1995to2014;studysample-sizerangedfrom58to2978,
withanaverageof807participants.Threestudieswereinternet-based(1US,1Norway,and1
USandNorway),whiletheremainingstudieswereconductedinsevencountries:6UK,5
Denmark,2Norway,2NewZealand,2US,and2Canada.The22includedstudiescontributed
63estimatesofminimumacceptableriskreduction:14studiescontributed28estimatesinthe
formofnumber-needed-to-treat(NNT);12studiescontributed22estimatesintheformof
absolute-risk-reduction(ARR)and6studiescontributed13estimatesintheformof
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prolongation-of-life(POL).Participantsweresampledfromthegeneralpopulationin13studies
(59%)andfromprimary-caresettingsin9studies(41%).Moststudieselicitedparticipants’
preferencesusingsingle-choicequestions(n=16;70%).Othermethodsweremultiple-choice
questions(n=4),iterativeprocess(n=1)ortrade-offmethod(n=1).Themostfrequentmethod
ofdatacollectionwasin-personinterviews(n=12;eithertelephoneorface-to-face);the
remainingstudiesusedsurveystocollectdatafromtheparticipants(eithermailedorinternet-
basedsurvey).CharacteristicsofincludedstudiesareshowninTable1.
Theresultsofthequalityassessment(Figure2)showedthathalfofthestudiestruly
representedthegeneralpopulation(n=11).Fewstudies(n=3)hadaresponserate≥75%,but
randomselectionorcensushadbeenundertakeninmoststudies(n=17).Datahadbeen
collectedusingthesamemethodsfromallparticipantsinmostincludedstudies(n=17).
ProlongationofLife(POL)
InstudieswhichpresentedtheCVbenefitsframedasPOL,39-73%oftheparticipants(average
54%)wouldconsidertakingcardio-preventivemedication.Thisdecreasedto39-54%(average
48%)whenweonlyconsideredpreventivemedicationsthatprolongedtheirlifebylessthan8
months,andincreasedto56-73%(average64%)whentheanalysiswasrestrictedtostudies
presentedPOLequaltoormorethan8(Figure3andeTable1intheSupplement).
Absoluteriskreduction(5-year)
InstudieswhichpresentedtheCVbenefitsintermofARR,42-89%oftheparticipants(average
60%)wouldconsidertakingtheCVDpreventivemedication.Thisdecreasedto42-72%
(average54%)whenweonlyconsiderstudieswheremedicationreducedthe5-yearabsolute
CVriskbylessthan3%,whilethispercentageincreasedto50-89%(average77%)whenwe
considerstudiespresentedARRequaltoormorethan3%(Figure4andeTable2inthe
Supplement).
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NumberNeededtoTreat(5-year)
InstudieswhichpresentedtheCVbenefitsintermofNNT,31-87%oftheparticipants(average
64%)wouldconsidertakingcardio-preventivemedications.Thisdecreasedto31-81%(average
60%)whenweonlyconsideredstudiespresentedamedicationneededtobetakenbymore
than30personstopreventoneeventwhilethispercentageincreasedto46-87%(average
71%)whenanalysisrestrictedtostudiespresentedNNTequaltoorlessthan30(Figure5and
eTable2intheSupplement).
FactorsaffectingthedecisiontocommenceaCVDpreventivetherapy
Somestudiesexploredotherfactorsthatwouldaffectthedecisiontotakeamedication.These
factorshelptoexplainsomeoftheheterogeneityobservedbetweenstudies.
Probabilisticvs.deterministic‘fixed’presentationofrisk
OnestudyfoundthatparticipantsweremorelikelytoagreetoaCVDpreventivetherapywhen
thebenefitswerepresentedasacertain,short,postponementofaheartattack(182/456;
40%)comparedtoanequalaveragebutuncertain‘probabilistic’longpostponementofthe
outcome(153/452;34%)19.ThiscognitivebiashasbeenalsoshownbyFinegoldetal25.
Participantspresentedwithacertain1-yearlifegainweremorelikelytoacceptamedication
thanwhenpresentedwitha10%chanceof10-yearlifegain(56%vs45%)25.However,if
participantswerepresentedwithtwogainsthatwerenotprobabilisticallyequivalent,they
preferredthetherapythatprovidesthelargergainwhetherpresentedasacertainoruncertain
benefit25.
PositiveversusNegativeframing
Carlingetal26foundthatparticipantsweremorelikelytoagreeforaCVDmedicationwhenthe
riskreductionwasframednegatively(66%)thanpositively(56%)orcomparedtoinformed
informationthatincludedpositiveandnegativeformattogether(40%and46%respectively).
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Similarly,Goodyear-Smith27foundthatparticipantsweremorelikelytoagreetotakingaCVD
medicationwhenthebenefitswereframednegatively(89%)thanpositively(80%).
Riskpresentationformat
Stovringetal28foundthattheproportionofrespondentswillingtotakeamedicationto
preventCVDwashigherwhenthebenefitwaspresentedaseitherARR(expressedinnatural
frequencies)orNNTcomparedtoPOL.Notably,POLwasfoundtohavetheleastconcordance
withfinaldecisionsthatwerebasedoncomprehensiveinformation(ARR,NNT,RRRand
pictorialpresentation).However,anotherstudyfoundmorepatientsconsideredtaking
medicationwhentheresultswerepresentedasARR(85%)thanNNT(67%)27.Carlingetal29
compareddifferentpresentationsofriskreduction,andfoundthatparticipantsweremore
likelytoconsideramedicationwhenthebenefitpresentedasrelativeriskreduction,but
naturalfrequencieswerescoredthehighestinpreference,understandingandsatisfactionwith
thepresentedinformation,andconfidenceinthedecision.
Addingadverseeffects
Friedetal30askedcommunity-livingolderpersonstheirwillingnesstoagreetoCVDpreventive
medicationswithvaryingdegreeofbenefitsandharms(bothtypeandseverity),andfound
thataboutahalfoftherespondentswhoinitiallyagreedtoamedicationwithaveragebenefit
withnoadverseeffectswereunwillingoruncertainabouttakingthesamemedicationifitwas
associatedwithevenmildfatigueandnausea,andonly3%ofthemwouldagreetoa
medicationthathadadverseeffectsthatcouldaffecttheiractivitiesofdailyliving.
PrevioushistoryorhighriskforCVD
ThepresenceofknownriskfactorsorahistoryofCVDmightalsoaffectthedecisiontotake
themedication.Forinstance,MisselbrookandArmstrong31foundthatpatientswithknown
highbloodpressureweremorelikelytoagreetoaCVDpreventivemedicationthan
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participantswithnormalbloodpressure,whichhasbeenalsofoundbyMcAlisteretal32.
SimilarfindingswerealsoshownbyTrewbyetal33comparingparticipantswithahistoryofCVD
andtakingmedicationstopatientseitherwithoutCVDhistorybuttakingapreventive
medicationorwithoutCVDhistoryandtakingnomedication.Similarly,Dahletalfoundthat
previoushistoryofmyocardialinfarction(OR:2.595%CI1.3-5.0),andelevatedcholesterollevel
(OR:1.995%CI1.8-2.6)significantlyincreasedtheoddsofconsentingtomedication34.Friedet
alfoundthatparticipantswhoratedtheirhealthaspoor/fairweremorelikelytoconsider
takingamedicationthanthoseratedtheirhealthasexcellent/verygood30.However,twoother
studiesfoundnoassociationbetweenself-reportedhealth,CVDhistoryandtheoddsof
consideringtakingmedication1935.
Participantbaselinecharacteristics
Malegenderwasfoundtobesignificantlyassociatedwithconsideringtakingamedicationin
Dahletal34,Halvorsenetal(2005)36,andHudsonetal3,but,notinHalvorsenetal(2007)19,
Nexoeetal37,andKristiansenetal35.Olderageandhighereducationlevelwassignificantly
associatedwithconsideringtakingamedicationinHalvorsenetal(2007)19,andKristiansenet
al35,but,notinNexoeetal37,Halvorsenetal(2005)36,andDahletal34.
PerspectiveofPatientsvs.Clinicians
McAlisteretal32comparedtheminimumgaininARRtoconsidertakingCVDmedication
betweenhypertensivepatients(withnoovertCVD)andfamilyphysicians,andfoundthat
patientsdemandgreaterbenefitsbeforeagreeingtoaCVDpreventivemedicationcompared
tophysicians.Similarly,Steel38foundthatthegaininARRtoagreetoanantihypertensive
medicationwasloweramongconsultantphysiciansthangeneralpractitioners,andhighest
amongthegeneralpublic.
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Discussion
Resultsofthe22studiesinthissystematicreviewsuggestthatanimplicitassumptionin
cardiovascularpreventionguidelines-thatparticipantsaccepttheamountbalancebetween
benefitsandharms-maynotbeconcordwithpatientpreferences.Eveninthestudieswhere
peoplewerepresentedwithanidealisedtabletwithnosideeffects,morethanone-third
statedtheywouldnotconsidertakingamedicationthatcouldpreventtheir5-yearabsolute
riskofacardiovasculareventbyanARRof5%ormore.ThisgainisrarelyachievedbyCVD
medication(e.g.statinreducetherelativeriskofaCVDeventbyabout5-yearCVabsoluterisk
byabout30%3940.Moreover,considerablevariationswereobservedinthepatients’
preferencesoftheminimumacceptableriskreductionofcardio-preventivemedication.
Severalfactorsmayexplainthewidevariationinpatients’preferencesbothwithinandacross
includedstudies,suchaswhetherpatientsarealreadytakingapreventivemedication,andthe
waythattheriskreductionhasbeencommunicatedtotheparticipants(e.g.riskpresentation
formatandframingeffect).Arecentsystematicreviewofriskcommunicationfoundthatthe
variousriskpresentationformatsmighthavedifferenteffectsonthedecisiontoconsider
takingmedication41.However,itisimportanttodistinguishbetweenthepersuasivenessofthe
riskpresentationformatsandtheclarityandunderstandabilityoftheformat18.Methodsused
toelicitpreferences(e.g.single-choiceoptions,trade-off)aswellasthoseusedtocollectdata
(face-to-faceinterviews,mailedquestionnaire)mayalsocontributetovariationobserved.
Lastly,thecharacteristicsofthemedicationpresentedtoparticipantsmayalsohaveaffected
theirdecisions.Anidealmedication(freeofchargeandnosideeffects)ismorelikelytobe
acceptedcomparedtoareal-lifemedicationwithcostsandpotentialsideeffects.
Thus,whenpatients’preferencesvarywidely,preventiveguidelinesshouldbewaryofsettinga
singleriskthresholdfortheinitiationofapreventivetreatment,basedontheeffectivenessof
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themedication.Anythresholdpointorrangeshouldbebasedonthebalanceofbenefitsand
downsides,whichshouldbeinformedbypatients’valueandpreferences.
StrengthandLimitation
Theheterogeneityofmethodsusedtoassessthepreferences,includingtrade-offmethod,
iterativeprocess,andsinglechoicequestionsisbothastrengthandlimitationofourstudy.The
inclusioncriteriameantthatawidevarietyofestimatescouldbeincludedinthereview,but
owingtothisheterogeneityofthemethodsandoutcomes,wecouldnotcalculatequantitative
summaryestimatesoftheminimumacceptableriskreduction,whichiscommoninsystematic
reviewsinthisfield174243.Moreover,mostoftheincludedstudieshavenotbeendesigned
primarilytoassessourresearchquestion,buttoexamineotherissuessuchasresponseto
framing.Inaddition,thereviewonlyconsidersthosefactorsreportedintheincludedstudies.
Anotherpotentiallimitationistheriskofmissingrelevantarticlesbecauseoftheuseofcitation
analysisasasearchstrategy.However,studiesinotherareassuggesttheaccuracyrateofthis
methodisacceptable(e.g.usingcitationanalysis,JanssensandGwinn retrievedabout94%
[75-100%]ofallincludedarticlesretrievedusingtraditionalmethodin10meta-analyses23).
Thus,wethinkthatouroverallresultsandconclusionareunlikelytobeaffected.
Implicationforclinicalpractice
Patients’preferencesshouldbeconsideredinbothguidelinedevelopmentandclinicalcare.
Patientsrepresentativesandmemberofthepublicshouldbeactivelyinvolvedinguideline
developmentpanels44.Futureguidelinesmustconsidermorethantheevidenceofmedication
effectivenessinestablishingtreatmentthresholds:Systematicreviewsofpatients’valuesand
preferencesshouldalsobeconductedtoinformguidelinerecommendations.Giventhe
heterogeneityinindividualpreferences,guidelinesshouldincludestrategiestohelpclinicians
incorporatepatients’preferencesandvaluestomakeinformeddecisions.Thiscanbeachieved
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bypromotingchoice,providingadequateinformationaboutthebenefitandrisksof
medication,andthelevelofuncertaintyintheevidence,andhighlightingthatguideline
recommendationssupport,butdonotsubstituteforclinicaljudgmentandindividualised
decision-making.Visualaids(e.g.iconarraysorriskpictograph)tocommunicateriskreduction
mightbeusedsinceevidenceshowsthatsuchaidsimprovepatients’understandingand
satisfaction41.Thisalsoimpliesthatthe‘doordonot’styleofrecommendationsshould
generallybediscouraged,andthatpreference-sensitiverecommendationsshouldnotbeused
asindicatorsofqualityofcare(qualitymeasures).
Cliniciansoftenfailtoaccuratelyidentifypatientpreferences–aproblemtermedsilent
misdiagnosis45,andhenceguidelinesshouldincludetoolsthatpromoteshareddecisionmaking
whereinterventionschoicescanbetailorednotonlytopatients’clinicalcharacteristicsbutalso
totheirvaluesandpreferences.Thismeansthatguidelinerecommendationsshouldbeusedas
astartingpointfortheindividualpatient-cliniciandecision-makingprocess.Inaddition,patient
versionsofguidelines,aswellasdecisionaidstools,shouldbedevelopedanddisseminated
alongwiththeguidelines.
Implicationforfutureresearch
Thissystematicreviewhighlightstheneedforstandardisingthekeymeasuresofpatient
preferencesthatmightbeusedtoinformguidelines.Futureresearchcouldgainfromusing
well-establishedmethodsforpreferenceelicitationusedinotherdisciplines(e.g.health
economics)todevelopavalid,reliable,andsensitivemeasureofpatientpreferencesina
medicaldecision-makingcontext.Moreover,asystematicreviewofqualitativestudies
regardingthefactorsaffectstheindividualdecisionofCVpreventivemedicationisalso
warranted.
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Conclusion
Evenforaside-effectfree,costlessmedication,manypatientsrequireasubstantialrisk-
reductiontoconsidertakingapreventivemedication.However,therangeofanswersisvery
widewithsomeacceptinganygain,andothernotwillingtoconsidermedicationwithanygain.
Guidelinesandclinicalconsultationsneedtoaccountforboththeseaverageandindividual
valuesinsettingriskthresholds.
ContributorsLA,JD,PGdesignedthestudy.LA,JD,PGscreenedthearticles.LA,JD,PGextracteddata.LAdraftedtheoriginalmanuscriptandallauthorsrevisedthepaper.LAistheguarantorofthestudy.
AcknowledgmentWewouldliketothankMsSarahThorningforherhelpwiththeliteraturesearch.
CompetinginterestsAllauthorshavecompletedtheICMJEuniformdisclosureformatwww.icmje.org/coi_disclosure.pdfanddeclare:DrGlaszioureportsgrantsfromNationalHeartFoundationpriortotheconductofthisstudy.Nosupportfromanyorganisationforthesubmittedwork;nootherrelationshipsoractivitiesthatcouldappeartohaveinfluencedthesubmittedwork.
FundingNospecificfundingforthisresearch
EthicalapprovalNotrequired.
DatasharingDataextractedfromtheincludedstudiesareavailableonrequestfromthecorresponding
author.
TheCorrespondingAuthorhastherighttograntonbehalfofallauthorsanddoesgrantonbehalfofall
authors,anexclusivelicence(ornonexclusiveforgovernmentemployees)onaworldwidebasistothe
BMJPublishingGroupLtdanditsLicenseestopermitthisarticle(ifaccepted)tobepublishedinHEART
editionsandanyotherBMJPGLproductstoexploitallsubsidiaryrights
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24.HoyD,BrooksP,WoolfA,etal.Assessingriskofbiasinprevalencestudies:modificationofanexistingtoolandevidenceofinterrateragreement.JClinEpidemiol2012;65(9):934-9.
25.FinegoldJA,Shun-ShinMJ,ColeGD,etal.Distributionoflifespangainfromprimarypreventionintervention.OpenHeart2016;3(1):e000343.
26.CarlingCL,KristoffersenDT,OxmanAD,etal.Theeffectofhowoutcomesareframedondecisionsaboutwhethertotakeantihypertensivemedication:arandomizedtrial.PLoSOne2010;5(3):e9469.
27.Goodyear-SmithF,ArrollB,ChanL,etal.Patientspreferpicturestonumberstoexpresscardiovascularbenefitfromtreatment.AnnFamMed2008;6:213-17.
28.StovringH,Gyrd-HansenD,KristiansenIS,etal.Communicatingeffectivenessofinterventionforchronicdiseases:whatsingleformatcanreplacecomprehensiveinformation?BMCMedInformDecisMak2008;8:25.
29.CarlingCLL,KristoffersenDT,MontoriVM,etal.TheEffectofAlternativeSummaryStatisticsforCommunicatingRiskReductiononDecisionsaboutTakingStatins:ARandomizedTrial.PLoSMed2009;6.
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36.HalvorsenPA,KristiansenIS.Decisionsondrugtherapiesbynumbersneededtotreat-Arandomizedtrial.ArchInternMed2005;165:1140-46.
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42.HoffmannTC,DelMarC.Patients'expectationsofthebenefitsandharmsoftreatments,screening,andtests:asystematicreview.JAMAInternMed2015;175(2):274-86.
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Figures
Figure1:Summaryofflowofinformationthroughthesystematicreviewprocess(PRISMAFlowDiagram)
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Figure2:Riskofbiasassessment:authors’judgmentsabouteachriskofbiasitem:(A)foreachincludedstudy(Riskofbiasgraph);and(B)presentedaspercentagesacrossallincludedstudies(riskofbiassummary).Representation:wasthesamplingframeatrueorcloserepresentativeofthetargetpopulation/generalpopulation;Selection:
wassomeformofrandomselectionused oracensusundertaken;Non-response:wasthelikelihoodofnon-responsebiasminimal(lowrisk:≥75%,highrisk:<75%);Datacollection:weredatacollecteddirectlyfromparticipantsandifthesamemode
ofdatacollectionusedforallparticipants.
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Figure3:Minimumacceptableriskreductionincardiovascularevents(expressedasProlongationof
Life)requiredbythepatientstojustifytakingdailypreventivemedication.Bubblegraphshowingthepercentageofparticipantsofincludedstudiesthatcouldaccepttakingamedicationagainstthe
potentialprolongationinlife(inmonthsinlogarithmicscale)forsuchamedication;thebubblearearepresentsthesample
size.
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Figure4:Minimumacceptableriskreductionincardiovascularevents(expressedasARR)requiredby
thepatientstojustifytakingdailypreventivemedicationBubblegraphshowingthepercentageofparticipantsofincludedstudiesthatcouldaccepttakingamedicationagainstthe5-
yearabsoluteriskreductionincardiovasculareventsthatcanbegainedbysuchamedication;thebubblearearepresentsthe
samplesize.
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Figure5:Minimumacceptableriskreductionincardiovascularevents(expressedasNNT)requiredby
thepatientstojustifytakingdailypreventivemedication.Bubblegraphshowingthepercentageofparticipantsofincludedstudiesthatcouldaccepttakingamedicationagainstthe
numberofindividualneededtobetreatedfor5yearstopreventonecardiovascularevent;thebubblearearepresentsthe
samplesize.
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Tables
Table1.Characteristicsofincludedstudies
Study Participants: Sample Size
(response rate%); Age; Women (%); data collection
Participants Characteristics Settings
Scenario: risk; medication; adverse event; side effects;
cost Outcomes
Carling, 2008, Internet-based46
770 participants; 62% between 40-59 years; 58% women; internet-based survey (in English)
Community (18+; internet-users); 90% educated to more than 12 years; 84% from USA; 23% GP or health professionals;
Hypothetical; single choice experiment; high cholesterol level; daily statin-like; 10-year CV risk of angina or heart attack; side effects of statins; 50US$ per month
To decide whether to take the medication or not based on a single value of risk reduction (ARR, NNT)
Carling, 2009, Internet-based29
2978 participants; 54% between 40-59 years; 59% women; internet-based survey (in English and Norwegian)
Community (18+; internet-users); 91% educated to more than 12 years; 42% from USA
Hypothetical; single choice experiment; high cholesterol level; daily statin-like; 10-year CV risk of angina or heart attack; side effects of statins; 50US$ per month
To decide whether to take the medication or not based on a single value of risk reduction (ARR or NNT)
Carling, 2010, Internet-based26
1528 participants; 49% between 40-59 years; 53% women; internet-based survey (in Norwegian)
Community (18+; internet-users); 59% educated to university-level
Hypothetical; single choice experiment; 40-yr old, non-smoker, active and has a healthy diet; high blood pressure level; daily; 10-year CV risk of stroke or heart attack; dizziness, impotence nausea, muscle cramps and others; co-payment
To decide whether to take the medication or not based on a single value of risk reduction, framed both positively and negatively (ARR)
Dahl, 2007, Denmark34
1367 participants (50%); mean age 60; 52% women; in-person interview
Community (40+); 32% had elementary education only; 5% history of heart attack and 18% hypercholesterolemia
Hypothetical; single choice experiment; high cholesterol level; daily; heart attack; few and harmless side effects; 60€ per year
To decide whether to take the medication or not based on a single value of risk reduction (POL)
Fontana, 2014, UK10
360 participants; mean age 38 years; 50% women; face-to-face interview
Community; 22% on regular medications; 1% history of previous CVD
Hypothetical; trade-off; high cholesterol level; daily statin-like; CVD and death; no side effects; negligible
Medical aversion (gain in lifespan required by participants to commence lifelong therapy); result was extracted from Figure1
Fried, 2011, US30
356 participants; mean age 76; 75% women; in-person interview
Community (senior centres); mean years of education was 13; 69% had more than 3 chronic conditions; 92% took 1 or more medication, with a mean of 4
Hypothetical; single choice experiment; multiple scenarios; primary CVD prevention; daily; 5-year MI risk; no side effects; covered by insurance
To decide whether to take the medication or not based on a single value of risk reduction (ARR) + pictograph
Goodyear-Smith, 2008, New Zealand27
100 participants (53%); mean 66 years; 60% women; telephone interview
Outpatients (4 family practices); patients eligible if they had heart disease and on statin;
Hypothetical; single choice experiment; angina or heart attack; daily statin-like; 5-year heart attack risk; few side effects;
To decide whether to take the medication or not based on a single value of risk reduction (ARR or NNT); negative framing
Halvorsen, 2005, Norway36
1201 participants (60%); 43% between 25-44 year; 48% women; face-to-face (or telephone) interview
Community; 28% educated more than 12 years; 11% history of hypertension, 8% hypercholesterolemia
Hypothetical; multiple choice experiment; multiple scenarios; angina or heart attack; daily statin-like; heart
To decide whether to take the medication or not based on a single value of risk reduction (3-year NNT)
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attack or stroke; no serious side effects; cost comparable to common cardio-preventive medication
Halvorsen, 2007, Norway19
1397 participants (81%); mean 58 years; 34% women; mailed questionnaire
Community; 23% educated more than 12 years; 21% previous CVD history
Hypothetical; single choice experiment; daily statin-like; heart attack; neither common nor dangerous side effects; refunded
To decide whether to take the medication or not based on a single value of risk reduction (5-year NNT, POL)
Hudson, 2012, New Zealand3
354 participants (36%); mean 60 years; 44% women; mailed questionnaire
Outpatients (3GPs, all registered 50-70 years); 31% educated to high school only; 13% previous CVD history
Hypothetical; single choice experiment; daily; death; no major side effects; 3$ per 3 months
To choose, from six different estimates (10-year NNT), the number of lives should be saved to justify lifelong medication
Hux, 1995, Canada9
100 participants; 53% older than 55 years; 47% women; questionnaire
Outpatients (35-65 years); 55% take cardiovascular medications; 70% history of heart disease; 62% attended cardiology clinic
Hypothetical; multiple choice experiment; daily statin-like; heart attack; negligible side effects; insured
To decide whether to take the medication or not based on a single value of risk reduction (5-year ARR, NNT, POL)
Kristiansen, 2002, Denmark35
675 participants (60%); mean age 44 years; 51% women; face-to-face interview
Community; 21% educated to elementary-level only; 3.3% previous CVD history
Hypothetical; single choice experiment; daily; heart attack; few and mild side effects; co-payment 55$ per year
To decide whether to take the medication or not based on a single value of risk reduction (3-year NNT)
Leaman, 2001, UK47
216 participants (41%); 40.5% between 50-69 years; 55% women; mailed questionnaire
Outpatients (single GP); the mean age at which respondents finished education was 16.7 years; 13% on antihypertensive medication; 2% previous MI
Hypothetical; iterative process; anti-hypertensive daily; heart attack; some side effects; some payment
To choose, from 6 different estimates (5-year NNT), the number of lives should be saved to justify lifelong medication; negative framing
Marshall, 2006, UK48
203 participants; median age 65; 13% women; face-to-face interview
Outpatients (13 Practices, No CVD history); mean years of education 15.5; 34.5% on long-term oral medications; 50% had less than 7.5% 5-year coronary risk
Hypothetical; multiple choice experiment; daily; heart disease; rare side effects;
To decide whether to take the medication or not based on a single value of risk reduction (5-year ARR); each one decide 6 times
McAlister, 2000, Canada32
74 participants (51%); mean age 49; 53% women; face-to-face interview
Outpatients (5 GPs and 4 internists, mild hypertension; no overt CVD); 69% educated to more than 12 years; 65% on antihypertensive
Hypothetical; multiple choice experiment; multiple scenarios; antihypertensive daily; death, MI, stroke;
Iterative process to achieve the smallest benefit (ARR) that justify lifelong medication (MCID)
Misselbrook, 2001, UK31
309 participants (102 hypertensive, 207 normotensive) (89%); aged 35-65 years; mailed questionnaire
Outpatients (single practice); patients excluded if illiterate, CVD, diabetes, disability, or mental illness
Hypothetical; single choice experiment; anti-hypertensive-like daily; stroke;
To decide whether to take the medication or not based on a single value of risk reduction (ARR, NNT)
Nexoe, 2005, Denmark37
2326 participants (50%); mean age 47 years; 56% women; face-to-face interview
Community; 26% educated to elementary-level
Hypothetical; single choice experiment; multiple scenarios; daily; death or heart attack; out of pocket payment
To decide whether to take the medication or not based on a single value of risk reduction (NNT)
Nicholson, 1999, UK49
384 participants (53%); mailed questionnaire
Outpatients (1 GP) Hypothetical; single choice experiment; statin-like daily; MI
To choose, from 4 different estimates (5-year NNT), the number of lives should be
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saved to justify lifelong medication
Sorensen, 2008, Denmark 50
1519 participants (49%); mean age 59; 53.9% women; face-to-face interview
Community; 6% previous heart attack; 17% hypercholesterolemia
Hypothetical; single choice experiment; daily; death or heart attack; mild and harmless side effects; 45€ per year
To decide whether to take the medication or not based on a single value of risk reduction (3-year RRR with baseline risk)
Steel, 2000, UK38
58 participants (58%); 45% 41-65 years old; 58% women
Community (39 practices) Single choice experiment; anti-hypertensive medication
To choose, from a five different estimates (5-year NNT), the number of lives should be saved to justify lifelong medication
Stovring, 2008, Denmark28
1169 participants (37%); aged 40-59; 57% women; face-to-face interview
Community; median years of education 13 years; 37% CVD history
Hypothetical; single choice experiment; multiple scenarios; statin-like daily; fatal heart disease; out of pocket
To decide whether to take the medication or not based on a single value of risk reduction (10-year ARR, NNT, POL)
Trewby, 2002, US33
307 participants (97%); mean age 61 years; 42% women; face-to-face (or telephone) interview
Both (3 groups: 1discharged from CCU; 2no MI history but on medication, 3neither history nor medication)
Hypothetical; single choice experiment; statin-like daily; heart attack; safe
Iterative process to achieve the minimum threshold (POL) that justify lifelong medication; extracted from Figure3