Aspirin and antiplatelet agents.docx

Aspirin and antiplatelet agents.docx

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Aspirinandantiplateletagents

Aspirinandantiplateletagents

Aspirinhasbeeninandoutoftheheadlinesfordecadesandremainsahugelypopulardrug110yearsafteritwasfirstpatented.Whileitsuseinthetreatmentofpainandfeverhasdiminished,duetotheavailabilityofnon-steroidalanti-inflammatorydrugs（NSAIDs）withbettersafetyprofiles,aspirinremainsthedrugofchoiceforpreventionofcardiovasculardisease（CVD）.Thepharmacologicalbasisforthedualanti-inflammatoryandantiplateletactivityofaspirinwasestablishedin1971byJohnVane,andmorerecentresearchhasidentifiedseveralothermechanismsofaction.

DespitethewidespreaduseofaspirinforthepreventionofCVD,theUKMedicinesandHealthcareProductsRegulatoryAgencyhashighlightedthataspirinisnotlicensedforthepreventionofheartattacksandstrokesinpeoplewithoutahistoryofvasculardisease（primaryprevention）,[1]astheriskofhavingamajorbleedwithaspirinmayoutweighanyvascularbenefit.[2]AspirinisonlylicensedintheUKforthepreventionofthromboticcerebrovascularandcardiovasculardiseaseinpeoplewhoalreadyhavevasculardisease（secondaryprevention）.[1]

Mostrecently,researchhasfocusedonapossibleroleforaspirininthepreventionofcancer.InFebruary2010,theJournalofClinicalOncologypublishedaprospectiveobservationalstudyshowingthataspirinmayreducetheriskofdeathfrombreastcancer.[3]Andarecentmeta-analysisofcancer-relateddeathsinrandomisedcontrolledtrialsofaspirinforpreventionofvasculardiseasefounda21%reductionintheoddsofdeathfromcancerinpeopletakingaspirinforalmostsixyears（OR0.79,95%CI0.68to0.92;p=0.003）.[4]However,theever-presentriskofseriousbleedingmeansthattherisk-benefitratioremainsuncertain.[5]

Thisspecialcollectiononaspirinandotherantiplateletagentsbringstogetherover20CochraneReviewsaddressingtheuseofsuchagentsinthepreventionandtreatmentofCVD.ThecollectionalsoincludesCochraneReviewsonthepreventionofcancer,andthetreatmentofinfertilityandrecurrentmiscarriage,dementiaandrenaldisease.TheCochraneReviewsinthiscollectionhavebeenpreparedbyabroadrangeofCochraneReviewGroupsandtheirauthors,includingtheColorectalCancerGroup,theDementiaandCognitiveImprovementGroup,theMenstrualDisordersandSubfertilityGroup,thePregnancyandChildbirthGroup,thePeripheralVascularDiseasesGroup,theRenalGroup,theStrokeGroup,theHeartGroupandtheHaematologicalMalignanciesGroup.

Cancerprevention

Nonsteroidalanti-inflammatorydrugs（NSAID）andaspirinforpreventingcolorectaladenomasandcarcinomas

ThereisevidencefromexperimentalanimalstudiesandfromprospectiveandretrospectiveobservationalstudiesthatNSAIDsmayreducethedevelopmentofsporadiccolorectaladenomasandcancerandmayinducetheregressionofadenomasinfamilialadenomatouspolyposis.ThisreviewevaluatestheeffectofNSAIDsforthepreventionorregressionofcolorectaladenomasandcancer.

Dementia

Aspirinforvasculardementia

Aspiriniswidelyprescribedforpatientswithadiagnosisofvasculardementia;inonestudy,completedbygeriatriciansandpsychiatristsintheUK,80%ofpatientswithclinicaldiagnosesofvasculardementiawereprescribedaspirin.However,anumberofqueriesremainunanswered.Isthereconvincingevidencethataspirinbenefitspatientswithvasculardementia?

Doesaspirinaffectcognition,behaviourorimproveprognosis?

Inaddition,doestheriskofcerebralorgastrichaemorrhageoutweighanybenefit?

Thisreviewassessestheevidenceofeffectivenessoftheuseofaspirinforvasculardementia.

Fertilityandpregnancy

Low-doseaspirinforinvitrofertilisation

Low-doseaspirinissometimesusedtoimproveoutcomesinwomenundergoinginvitrofertilisation,despiteinconsistentevidenceofefficacyandthepotentialriskofsignificantside-effects.Themostappropriatetimetocommenceaspirintherapyandthelengthoftreatmentrequiredarealsostilltobedetermined.Thisreviewaimstodeterminetheeffectivenessoflow-doseaspirinforimprovingtheoutcomeofinvitrofertilisationandintracytoplasmicsperminjectiontreatmentcycles.

Preventionofrecurrentmiscarriageforwomenwithantiphospholipidantibodyorlupusanticoagulant

Severaltreatmentshavebeenproposedtoimprovepregnancyoutcomeinrecurrentpregnancylossassociatedwithantiphospholipidantibody.Smallstudieshavenotresolveduncertaintyaboutbenefitsandrisks.Thisreviewexaminestheoutcomesofalltreatmentsgiventomaintainpregnancyinwomenwithpriormiscarriageandantiphospholipidantibody.

Aspirinoranticoagulantsfortreatingrecurrentmiscarriageinwomenwithoutantiphospholipidsyndrome

Sincehypercoagulabilitymightresultinrecurrentmiscarriage,anticoagulantagentscouldpotentiallyincreasethelive-birthrateinsubsequentpregnanciesinwomenwitheitherinheritedthrombophiliaorunexplainedrecurrentmiscarriage.Inthisreview,theefficacyandsafetyofanticoagulantagents,suchasaspirinandheparin,areevaluatedinwomenwithahistoryofatleasttwomiscarriageswithoutapparentcausesotherthaninheritedthrombophilia.

Antiplateletagentsforpreventingpre-eclampsiaanditscomplications

Pre-eclampsiaisassociatedwithdeficientintravascularproductionofprostacyclin,avasodilator,andexcessiveproductionofthromboxane,avasoconstrictorandstimulantofplateletaggregation.Theseobservationsledtothehypothesisthatantiplateletagents,low-doseaspirininparticular,mightpreventordelaydevelopmentofpre-eclampsia.Thisreviewaimstoassesstheeffectivenessandsafetyofantiplateletagentsforwomenatriskofdevelopingpre-eclampsia.

Renaldisease

Medicaladjuvanttreatmenttoincreasepatencyofarteriovenousfistulaeandgrafts

End-stagerenaldisease（ESRD）patientsoftenrequiretheformationofanarteriovenous（A-V）fistulaoranA-Vinterpositionprostheticshuntforhaemodialysis.ThisreviewassessestheeffectsofadjuvantdrugtreatmentonthepatencyoffistulaeandgraftsinpatientswithESRDwhoareundergoinghaemodialysisbyassessingthenumberofthromboticepisodes.

InterventionsforpreventingandtreatingkidneydiseaseinHenoch-SchönleinPurpura（HSP）

Henoch-Schönleinpurpura（HSP）isaprimarysmall-vesselvasculitis.GlomerulonephritisisoneofthemajorcomplicationsofHSP.Thisreviewevaluatesthebenefitsandharmsofvariousagents（usedsingularlyorincombination）usedforthepreventionortreatmentofkidneydiseaseinpatientswithHSP.

Interventionsforhaemolyticuraemicsyndromeandthromboticthrombocytopenicpurpura

Haemolyticuraemicsyndrome（HUS）andthromboticthrombocytopenicpurpura（TTP）arerelatedconditionswithsimilarclinicalfeaturesofvariableseverity.SurvivalofpatientswithHUSandTTPhasimprovedgreatlyoverthepasttwodecadeswithimprovedsupportivecareforpatientswithHUSandbytheuseofplasmaexchangewithfreshfrozenplasmaforpatientswithTTP.Separatepathogenesisofthesetwodisordershasbecomemoreevident,butmanagementoverlaps.ThisreviewevaluatesthebenefitsandharmsofdifferentinterventionsforHUSandTTPseparately,inpatientsofallages.

StrokeandCVDprevention

Primarypreventioninhigh-riskgroups

Antiplatelettherapyforpreventingstrokeinpatientswithnon-valvularatrialfibrillationandnoprevioushistoryofstrokeortransientischemicattacks

Non-valvularatrialfibrillation（AF）carriesanincreasedriskofstrokemediatedbyembolismofstasis-precipitatedthrombioriginatingintheleftatrialappendage.Thevalueofantiplatelettherapyforprimarystrokepreventioninpatientswithnon-valvularAFmeritsconsiderationbecauseofthesuspectedcardioembolicmechanismofmoststrokesinAFpatients.Thisreviewassessestheefficacyandsafetyoflong-termantiplatelettherapyforprimarypreventionofstrokeinpatientswithchronicnon-valvularAF.

Oralanticoagulantsversusantiplatelettherapyforpreventingstrokeinpatientswithnon-valvularatrialfibrillationandnohistoryofstrokeortransientischemicattacks

Non-valvularatrialfibrillation（AF）carriesanincreasedriskofstroke.Primarystrokepreventioninpatientswithnon-valvularAFpotentiallymeritsconsiderationbecauseofthesuspectedcardio-embolicmechanismofmoststrokesinAFpatients.Theaimofthisreviewistocharacterisetherelativeeffectoflong-termoralanticoagulanttreatmentcomparedwithantiplatelettherapyonmajorvasculareventsinpatientswithnon-valvularAFandnohistoryofstrokeortransientischaemicattack.

Antiplateletagentsandanticoagulantsforhypertension

Althoughelevatedsystemicbloodpressureresultsinhighintravascularpressure,themaincomplications（coronaryheartdisease,ischaemicstrokes,peripheralvasculardisease）arerelatedtothrombosisratherthanhaemorrhage.Somecomplicationsrelatedtoelevatedbloodpressure,heartfailureandatrialfibrillation,arethemselvesassociatedwithstrokeandthromboembolism.Useofantithrombotictherapymaybeparticularlyusefulinpreventingthrombosis-relatedcomplicationsofelevatedbloodpressure.Thisreviewevaluatestheroleofantiplatelettherapyandanticoagulationinpatientswithhighbloodpressure.

Antiplateletagentsversuscontroloranticoagulationforheartfailureinsinusrhythm

Morbidityandmortalityinpatientswithsymptomaticchronicheartfailurearehigh,andtheconditionpredisposestostrokeandthromboembolism,whichinturncontributetohighmortalityinheartfailure.Thisreviewdeterminestheeffectofantiplateletagentswhencomparedwithplacebooranticoagulanttherapyonde