Key messages

• Peoplewithatrialfibrillationonaspirin,clopidogrelornoantithromboticmedicationshouldbereviewedtoassesssuitabilityofanticoagulation.

• Warfarinorneworalanticoagulantsmaybesuitableafteraninformeddiscussionwiththepatient.

• Aspirindoesnotsignificantlyreducestrokeinatrialfibrillation.Atolderagesbleedingmayresultinnetharm.

SUMMARY GUIDELINES

ISBN 978-0-902238-96-1

Atrial fibrillation Improving anticoagulation: update

Aim of the guideline

Onlyhalfthepeoplewithatrialfibrillationareonanticoagulantswhichreducestrokesby64%.

Thisguidanceaimstoincreasetheuseofanticoagulantsandreducetheinapproriateuseofantiplateletagents.

What this guidance covers

Theguidanceconcernsantithromboticagentsforthetreatmentofnon-valvularatrialfibrillation.ItisconsistentwithNICEGuidance.

OCTOBER 2014

See 2014 NICE AF guideline 180guidance.nice.org.uk/cg180

2 IMPROVING ANTICOAGULATION

IMPROVING ANTICOAGULATION 3

Contents

p3 Aims and issues

p3 What you can do

p4 Aspirin in AF

p5 Flowchart

p6 APeL and GRASP tools

p7 AF investigation

P8 CHADS2 and CHA2DS2-VASc

p9 Bleeding and HAS-BLED

p10 New oral anticoagulants

p11 Atrial devices

p13 Switching to NOACs

Authors

JRobson,SAntoniou,PMacCallum,RSchilling,PGompertz,IStaveley.

Wearegratefulforadvicefrom:prescribingadvisors(EastLondonConsortium)BBrese,REnti,YHossenbaccus(NHSOuterNorthEastLondon)OChesa,BKrishek.

Haematologists:WMills,ATso,MEvans,LGreen,LBowles,NAkhtarCardiologists:AWragg,GLip.Generalpractitioners:SSen,SSelvaseelan,JJagens,PCockman,SHull,KBoomla,BHart,

CEGstaff:KPrescott,IDostalfortheAPeLtool

CEG Website

ThisguidelineisavailableontheCEGwebsiteblizard.qmul.ac.uk/ceg-resource-library.html

Contact Us

AnyqueriesregardingthisdocumentshouldbeaddressedtoCEGatihse-ceg-admin@qmul.ac.uk58TurnerSt,LondonE12AB

Tel:02078822553

Guidance

Thisdocumentisaguidetodecisionmakingandnotareplacementforclinicaljudgement.WehavebasedthisguidancelargelyontheEuropeanSocietyofCardiology2012atrialfibrillationguideline.

4 IMPROVING ANTICOAGULATION

Aim

Thisguidanceisintendedforuseinpatientswhohavealreadybeendiagnosedandclinicallyevaluatedwithnon-valvularatrialfibrillation.

•ThisguidanceaimstoincreaseanticoagulationinpeoplewithAF.Warfarinisthedrugoffirstchoiceunlesscontraindicated.

•Italsoidentifiestheroleofneworalanticoagulants(NOAC)suchasdabigatran,rivaroxaban,andapixabanandtheiradvantagesanddisadvantages.

•ItaimstoreducetheuseofantiplateletagentsinAFasthereislittleevidencetheyreducestroke.

The issues

•AFcauses20%ofstrokes=12,500pa1.

•Strokeriskis5-6timesgreaterinAFpatientsthaninsinusrhythm1.

•40%ofpatientsareonaspirinalthoughanticoagulantsreducestrokemoreeffectively2.

•Warfarinreducesstrokeriskby64%comparedtoplacebo3.NOACsaresimilarlyeffective.

•Aspirinonlyreducesthisriskby19%(nonsignificant)4.

•Neworalanticoagulantsshouldbeconsideredinpeopleunsuitableforwarfarin5.

References

1.www.medman.nhs.uk/ebt/merec/cardio/atrial/resources/merec_bulletin_vol12_no5.pdf

2. Mathur et al. Ethnicity and stroke risk in AF . Heart. 2013;99:1087-92.

3. NHS Improvement. Commissioning for Stroke Prevention in Primary Care – the role of atrial fibrillation 06/09

4. Mant et al Warfarin versus aspirin for stroke prevention. Lancet 2007;370: 493-503.

5. NICE HTA guidance 2012

6. European Society of Cardiology. Atrial fibrillation 2012

What you can do

Use APL or GRASP tools to review all

patients with AF and their stroke risk

with the CHADS2 or CHA2DS2-VASc and

HAS-BLED scores to consider whether

anticoagulation will reduce stroke without

excessive risk of bleeding.

Re-discuss reasons for not using anticoagulant

•Peopleonaspirinaretwotothreetimesmorelikelytohaveastrokeaspeopleonwarfarin.

•Warfarin‘contraindications’areoftenoverestimated.

•Riskoffallsarerarelyareasonnottouseanticoagulants.

•Ifadherenceisanissue,willthisbebetterwithaNOACwhichmaybemonitoredlessfrequently?

•IfthereisatruecontraindicationtowarfarinconsideruseofaNOACorreferralifindoubt.

•Ifbloodtestsremaintheobstacleconsiderreferralforaneworalanticoagulant(NOAC).

•Wherethereisdoubt,referforreassessmentbyhaematologist.

If bleeding is a risk should this be reassessed?

•Bleedingriskandseveritywithaspirinisasgreat,ifnotgreater,thanwithwarfarinatolderages.

•UsetheHAS-BLEDscore.Useanticoagulantswithcautionifthescoreis3ormore-discusswithhaematologist;morefrequentreviewmayberequired.

•Ifpreviousbleedingbutnomajorbleedwithin3years,discusstreatmentoptionswithhaematologist.

•Ifbleedingisanissueistherearoleforatrialablation?Seep11.

IMPROVING ANTICOAGULATION 5

AF without other CVDFor people with AF but who do not have IHD, stroke or TIA, aspirin can no longer be recom-mended as there is no evidence that benefits outweigh risks7.

When anticoagulants cannot be used

Aspirin and/or clopidogrel should only be considered where warfarin and NOACs cannot be used due to allergy or contraindications.

PrimaryPrevention

Noantithrombotic

Stroke/TIA ClopidogrelStableangina LowdoseaspirinOldMI LowdoseaspirinNewMI/ACS Dualantiplatelet:aspirin

pluseitherclopidogrel,ticagrelororprasugrelfor1yr

Aspirin in AF AspirinisnoteffectiveinstrokereductioninAF7.

WarfarinorNOACscombinedwithaspirinorclopidogrelisnotadvisableinmostcircumstancesandpatientsonthiscombinationshouldbereviewedwithaviewtostoppingantiplateletagents.Theincreasedriskofbleedingusuallyoutweighsthereductionofstroke8.ApatientwithAFafteruncomplicatedMIorstrokewillusuallybetreatedwithwarfarinaloneSeep.8forpatientswhomaybeonwarfarinandanantiplateletagentafterrecurrent MI,coronarystentsorothercoronarycomplexitywhoshouldbediscussedwiththecardiologist.

Risk of major bleedOverage80yearsbleedingriskwithaspirinisashigh,ifnotgreaterthanwithwarfarin4.

The BAFTA AF Trial4

RCTofwarfarinvs.aspirin75mginatrialfibrillation

•973patientswithAF;meanage=82yrs

•Strokeriskwashalvedinthewarfaringroupincomparisontothoseonaspirin

•50peoplewouldneedtobetreatedfor1yearwithwarfarinratherthanaspirintopreventonestroke(approx10peoplein5yrs)

•Therewasnoincreasedbleedingriskwithwarfarinincomparisonwithaspirin

Thereisnosubstantiveevidencethataspiriniseffectiveinpreventingstrokeinpeoplewithatrialfibrillationandtherisksofmajorbleedingoutweighthepossiblebenefitsatolderages.

Wherepatientshaveco-morbidCVDbuttheyareunable totakewarfarinorneworalanticoagulants,thenaspirinwithorwithoutclopidogreloranotherantiplateletagentiswillreducetheriskofrecurrentCVDevents.Seenextcolumn.

7. www.rcpe.ac.uk/sites/default/files/files/supplement-18.pdf

Age yrs Warfarin Aspirin Rel. Risk

75-79 1.1% 0.8% 1.44

80-84 2.3% 2.4% 0.9685+ 2.9% 3.7 0.77

Whiletheriskofstrokeisreducedwiththecombina-tionofaspirin/clopidogreloveraspirinalone,theriskofmajorbleedingisalsosignificantlyincreased.PPIstoreducegastrointestinalbleedingriskwithantiplateletagentsshouldbeusedwhereappropriate.

Ifanticoagulantscannotbeused,cliniciansrecommendthatforstroke/TIA:clopidogrelisthepreferredchoice*.

Clopidogrelafter/strokeTIAisrecommendedasintrials,dipyridamolewasmorelikelytobediscontinuedbecauseofheadacheandclopidogrelwascheaperandatleast,ifnotmoreeffective.

ForACS/STEMIandNSTEMI*dualantiplateletherapy-acombinationofaspirinplusclopidogrelorticagrelororprasugrelshouldbecontinuedforthefirstyear.

*NICEwasunabletorecommendclopidogrelforTIA/STEMIbecauseclopidogrelisnotlicensedforthisuse.TheselocalvariationsareacceptedbyCCGprescribingadvisorsassatisfactoryalternatives.

8. Oldgren J, Wallentin L, Alexander JH. New oral antico-agulants in addition to single or dual antiplatelet therapy after an acute coronary syndrome: a systematic review and meta-analysis. Eur Heart J. 2013;34:1670-80.

6 IMPROVING ANTICOAGULATION

Bleeding risk?

Major bleed or HAS-BLED ≥ 3 ? Do benefits of anticoagulation outweigh risks of bleed?

Consider NOACs if ... warfarin allergy/contraindications unable to adhere to monitoring unable to achieve INR in range patient preference after informed discussion

GFR >50 ml/min

Age <75 yrs Weight >60 kg

Age >75-80 years; weight <50-60kg or GFR 30-50 ml/min or less See BNF. Indications for reduced dose differ.

Dabigatran GFR<30 ml/min Apixaban/rivaroxaban GFR <15 ml/min

Apixaban, dabigatran or rivaroxaban dose based on age, weight & GFR (Note*: use Cockcroft Gault for GFR rather than eGFR)

Dabigatran 150mg BD Apixaban 5mg BD Rivaroxaban 20mg OD

Dabigatran not advised previous MI Reduce dose if additional bleeding risk

Dabigatran 110mg BD <75yrs <50kg Apixaban 2.5mg BD <80 yrs <60kg Rivaroxaban 15mg OD Consult haematologist for advice. If GFR< 50ml/min use Cockcroft Gault to calculate GFR.

NOT suitable

CHA2DS2VASC Score

Score = 0 No antithrombotic or antiplatelet necessary

Warfarin or NOAC after an informed discussion with patient

Men score ≥ 1 Women ≥ 2 or age ≥ 65 yrs

Anticoagulation not suitable: only use aspirin +/-clopidogrel or other antiplatelet agent if previous CVD. See text for detail.

Anticoagulation in atrial fibrillation

IMPROVING ANTICOAGULATION 7

APeL tool

CEGdevisedtheAPeLtool:APeLAtrialfibrillationProgrammeeLondon.ThisworksinasimilarwaytoGRASPasanaidinclinicaldecisionmaking,andcalculatesthemorerecentCHA2DS2-VAScscorewhichpredictstheriskofstrokeinpeoplewithatrialfibrillationandtheHAS-BLEDscoreswhichpredictsriskofbleeding.

CHADS2andCHA2DS2-VAScarenowcalculatedautomaticallywithinEMISandalsobytheAPeLtoolwhichdisplaysbothpreviouslycalculatedandthelatestscoretoshowwherethesearemissingorrequireupdating.Datashowsfurtherrelevantclinicaldetailsincludingdementia,palliativecare,alcoholconsumption,fallsandco-morbiditiesforindividualpatients.

ThescreenshotbelowshowsanexampleoftheAPeLmaindisplayshowingpeopleonaspirinorclopidogrel.

APeLcanbeadaptedforanycomputersystemandisavialablefromtheClinicalEffectivenessGroupQMUL.

GRASP-AF

NationallytherehavebeenmajorattemptstoimproveanticoagulationusingtheGRASP-AFtoolthatextractsdatafromGPrecords.ItisdescribedontheNHSImprovementwebsite.

Nationallythishasimprovedwarfarinanticoagulationbyamodestamount(52%to54%).

GRASP-AFissupportedbyPRIMIS.Downloadfrom:

www.primis.nottingham.ac.uk/AF_CHADS/NHS_Improvement_files/PRIMIS_GRASPAF_Register.htm

Health Analytics

InouterNorthEastLondonHealthAnalyticalsoprovidesimilardisplaysofpatientsatrisk.ForfurtherdetailscontactCliveSutherlandatClive.Sutherland@onel.nhs.uk

QOF 2013

FromApril2012QOFrequiresCHADS2calculationinallpatientswithAF.WerecommendGPsusebothCHADS2andCHA2DS2-VAScscorestofitwithQOF.

APeL Tool example: those on aspirin in a practice patient and GP details removed in this

TheEMISandAPELCHADSscoresmaydifferbecausethetabledisplaysthelastscoreenteredinthepatientsrecordintheEMIScolumnandthenewlycalculatedscoreintheAPELcolumn.

8 IMPROVING ANTICOAGULATION

AF causes and investigation

Valvular heart disease Lung cancer

IHD, heart failure Obesity

Cardiomyopathy Alcohol

Thyroid disease Sleep apnoea

Diabetes Family history: AFor premature CVD

Renal disease Hypertension

ThediagnosisofAFshouldalwaysincludea12leadECGandasearchforconditionsthatpredisposetoAF.

FBC,U&E/GFR,proteinuria,ALT,thyroidfunctiontests,fastingglucose/HbA1c,CXR,12leadECG.

AnechocardiogramtoshowcardiacabnormalitiesoratrialthrombusisadvisedinallnewcasesofAF.

NotetheneedforCockcroftGaultGFRratherthaneGFRinpeopleover80yearsorthosewithpoorrenalfunction.(seedetailslater).

Decision to treat

Thedecisiontoanticoagulateshouldconsider

•Riskofstroke;CHA2DS2-VAScscore.

•Riskofbleeding;HAS-BLEDscore.

•Inabilitytomanagemedicines/monitoring.eg.mentalimpairment,alcoholism,etc.

•Theriskoffalls–bleedingriskisgenerallylessthantheriskofastrokeandfallsarerarelyareasonfornotusinganticoagulants.

•Co-morbidities:Riskincreaseswithco-morbidconditions-seeCHADSscores.

Referral

Considerreferralforfurtherassessmentorobtainconsultantadvice,

• wherethereisdoubtabouttheratioofbenefitstorisksofanticoagulation.

• inthoseunder65yearsorthosewithcomplexco-morbidityordruginteraction.

• Patientsunsuitableforwarfarinshouldbeconsideredforneworalanticoagulants.

• Consideratrialablationwherebleedingprecludesanticoagulant.

Paroxysmal AF and atrial flutter

Strokeandthrombo-embolicriskinparoxysmalAFandatrialflutterissimilartopersistentAFandantithrombotictherapyisrecommendedforthesepatients.Reversiontosinusrhythmmaybeintermittentandisnotareasontostoptherapy.

Warfarin plus aspirin/clopidogrelAddingeitheraspirinand/orclopidogreltowarfarinorNOACs,usuallyincreasesbleedingrisktoamuchgreaterextentthananyreductioninCVDandtheadditionofanantiplateletagenttowarfarinorNOACsisnotgenerallyrecommended.

However,somepatientsatveryhighriskwhohaveeitherhadanMIwhilstonwarfarinorafterstentingorothercomplexcardiacinterventionsmayrequirebothwarfarinandantiplateletagentsforadefinedperiod;usuallyayear.

Peopleonbothantiplateletagentsandwarfarinshouldbereviewedandconsiderationgiventostoppingantiplateletagentsunlessthereisaclearindicationfortheiruseagreedwithcardiologistsorotherspecialities.

IMPROVING ANTICOAGULATION 9

CHA2DS2-VASc and CHADS2 scores

TheCHA2DS2-VAScscoreisamoreaccurateindicatorofriskthantheearlierCHADS2score9.

Patients at low risk:Patientsaged<65years(bothwomenandmen)withloneAFandnoothermajorriskfactors:No antithrombotic therapy is usually the preferred option.

One or more risk factors:anticoagulation with warfarin is the preferred first option in men and in women aged ≥ 65 years or women score ≥ 2

Neworalanticoagulantsareanoptionifwarfarinisunabletobeused.

AspirinorclopidogrelareonlyrecommendedifthepatientisathighCVDriskandanticoagulantscannotbeused.

CHADS2 Risk Factor CHA2DS2-VASc

1

Congestive heart failure/LV dysfunction

1

1 Hypertension 1

1 Age ≥75 y 2

1 Diabetes mellitus

1

2 Stroke/TIA/embolism

2

IHD, peripheral artery disease

1

Age 65–74 y 1Female* 1

*Female = 0 if under 65 yrs no other risks

Calculating CHA2DS2-VASc

ForpatientswithAF,tocalculatethescoresimplysumeachpoint.Forexample,a67-year-oldwomanwithdiabetesandhypertensionhasascoreof:Age=1,Female=1,Diabetes=1,Hypertension=1TotalScore=4.EMIScalculatesthisautomaticallyNB. Women under 65 no risks = 0, F ≥ 65 yrs = 2

Risk of stroke and CHA2DS2-VASc 9,10

CHA2DS2-VASc re

Stroke 1 yr

/100

Stroke 5 yrs

/100 0 0.9 4.5 1 2.2 5.5 2 2.2 12.0 3 6.3 17.0 4 7.8 21.0 5 8.4 19.0

Review of AF

ThereviewofpatientswithAFnotonanticoagulantsshouldincludethebenefits,risks,andcontinuingneedforantithrombotictherapy.

•Assessstrokeriskandbleedingriskbeforestartinganticoagulation.

•DespiteanticoagulationofmoreelderlypatientswithAF,ratesofintracerebralhaemorrhageareconsiderablylowerthaninthepast,typically1to5/1000pa.IntracranialbleedingincreaseswithINRvalues3.5–4.0ormore.ThereisnoincreaseinriskwithINRvalues2.0-3.0comparedwithlowerINRlevels.

•Aspirinhasasimilarmajorbleedingrisktowarfarininelderlypeople.

•Concernaboutfallsmaybeoverestimated,asapatientmayneedtofall300timesperyearfortheriskofintracranialhaemorrhagetooutweighthebenefitoforalanticoagulantsinstrokeprevention6.

9. Lip GYH. J of Thrombosis and Haemostasis 2011; 9 (Suppl.1):344-351

10. Larsen et al. Added predictive ability of CHA2DS2-VASc risk score for stroke and death in patients with atrial fibrillation. Circulation 2012;5.Doi:10.11.61

10 IMPROVING ANTICOAGULATION

Bleeding and HAS-BLED

Anewbleedingriskscore,HAS-BLED(hypertension,abnormalrenal/liverfunction,stroke,bleedinghistory,labileINR,elderly(>65),drugs/alcoholconcomitantly),hasbeenvalidated.

Ascoreof≥3indicates‘highrisk’,andregularreviewadvisedwhetheronanticoagulantoraspirin.

Risk Factor Score

H Hypertension(≥160mmHg)

1

A Abnormalrenalandliverfunction1pointeach

1 or 2

S Stroke(haemorrhagicorischaemic)

1

B Bleeding 1 L LabileINRs 1 E Elderlyage≥65years 1 D Drugsoralcohol

1pointeach1 or 2

Max 9 pts

•Hypertension’isdefinedassystolicbloodpressure160mmHgormore.

•‘Abnormalkidneyfunction’=renaldialysis,renaltransplantationorserumcreatinine≥200mmol/L.

•‘Abnormalliverfunction’=chronichepaticdisease(e.g.cirrhosis)orbiochemicalevidence(e.g.bilirubin2xupperlimitofnormal,inassociationwithAST/ALT3xupperlimitnormal)

•‘Bleeding’referstopreviousbleedinghistoryand/orpredispositiontobleeding,e.g.bleedingdiathesis,anaemia,

•‘LabileINRs’referstounstable/highINRsorpoortimeintherapeuticrange(e.g.<60%)

•Drugs/alcoholusereferstoconcomitantuseofdrugs,suchasantiplateletagents,non-steroidalanti-inflammatorydrugs,oralcoholexcess,etc.

Perioperative anticoagulation

Localpoliciesshouldbefollowed.PatientswithAFwhoareanticoagulatedrequiretemporaryinterruptionoftreatmentbeforemostbutnotalltypesofsurgery.ManysurgeonsrequireanINR≤1.5beforeundertakingsurgery.Ifwarfarinisused,(half-lifeof36–42hrs),treatmentshouldbeinterrupted3-5daysbeforesurgerytoallowtheINRtofallappropriately.Warfarinshouldberesumedatthe‘usual’maintenancedose(withoutaloadingdose)ontheeveningof(orthemorningafter)surgerydependingonbleedingrisk.Subcutaneouslowmolecularweightheparinisoftenusedasabridgingtherapyinpeopleundergoingoperativecareorawaitingoralanticoagulation.

ForpatientsonNOAC’swhorequiresurgery,experienceislimitedatpresentandspecialistadviceshouldbesoughtinadvance

Community anticoagulant monitoring

ProgrammesforpracticebasednearpatienttestingforINRhavebeensuccessfullyestablishedinmanyCCGs,coveringupto60%ofthosewithAFrequiringwarfarinmonitoring.TheseclinicsarelargelyGPpracticebasedinsomeCCGs,andamixtureofpharmacyandGPbasedinothers.Intrialstheseprogrammeswereassociatedwithsimilarlevelsoftimeintherapeuticrangeandhadhigherlevelsofpatientsatisfaction,betteraccessibilityandsubstantiallylowerpatientcoststhancentrallyrunhospitalbasedschemes.

Thereareasmallnumberofpatientswhoeitherself-testtheirownINRsusingapurchasedpoint-of-caredeviceanddoseadjustwithadvicefromtheirlocalanticoagulantserviceorself-manage,ie.doboththeirownINRtestingandwarfarindoseadjustment.Thesepatientsshouldbelinkedtoalocalanticoagulantserviceforcontinuingclinicalreviewandforexternalqualitycontrolpurposes.

IMPROVING ANTICOAGULATION 11

New oral anticoagulants: apixaban, dabigatran and rivaroxaban

Incomparativetrialsthesenewdrugswereatleastaseffectiveaswarfarininreducingstroke.Theoverallriskofmajorbleedingdidnotdiffersignificantlybetweenwarfarin,dabigatranandrivaroxabanbutoverallbleedingwasreducedwithapixaban.NOACsreducedintracerebralhaemorrhageincomparisontowarfarin.

IntrialsNOACshavefewerdruginteractionsbutthereareneverthelesssomeimportantdruginteractionsandexperienceinwideruseislimited.NOACshavetheadvantagethattheydonotrequirebloodtestsformonitoring.However,fewervisitsmaymeanlessadherence–evenintrialsabout20%ofpatientsdiscontinuedeitherNOACorwarfarin.

NOAC indications

NICEguidanceconsidersthechoiceofwarfarinorNOACforanticoagulatiuonshouldbemadeafteraninformeddiscussionwiththepatintaboutrisksandbenefitsinrelationtothepatientsclinicalfeatures,patientpreferencesorfactorsthatmayinfluencetheirabilitytomonitortreatmentorsustainconcordancewithtreatment.

NOACsareappropriateforpatientswhoareunable:

•totakewarfarinduetocontraindications.

•toadheretothemonitoringrequirementsassociatedwithwarfarintherapy.

•toachieveanINRinthetargettherapeuticrangedespiteadherencetotreatment.TTR<65%.

(It is doubtful whether NOAC have advantages in people who are not adherent to treatment).

11.ConnollySJ,EzekowitzMD,YusufS,etal.Dabigatranversuswarfarininpatientswithatrialfibrillation.NEJM2009;361:1139-51.

12.PatelMR,MahaffeyKW,GargJ,etal.Rivaroxabanversuswarfarininnonvalvularatrialfibrillation.NEJM2011;365:883-91

NOAC evidence

TrialswithdabigatranandrivaroxabanselectedpeopleinAFathighriskofastroke(typicallyCHADS≥2).

WithallthreeNOACstherewerefewerintracranialhaemorrhages.

Forstrokereduction,rivaroxabananddabigatran110mgwereshowntobenon-inferiortowarfarin.Dabigatran150mgBDandapixaban5mgBDbothshowedasignificantreductionintheprimaryoutcome;strokeandsystemicembolism.

IntheRELY11trialwithdabigatran,therewasnodifferenceintherateofmajorbleedingwiththe150mgBDdose,whereasthe110mgBDdoseshowedsuperiorityoverwarfarinformajorbleeding.Bothdosesdemonstratedahigherincidenceofmajorgastrointestinalbleedingthanwarfarin.

Warfarinwasmoreeffectivethandabigatraninreducingmyocardialinfarctionanddabigatranisnotadvisedinpeoplewithischaemicheartdisease.RivaroxabanandapixabanshowednosignificantdifferenceinMIreduction.

IntheROCKET12trialwithrivaroxabantherewasnosignificantdifferenceinmajorbleeding,fewerfatalbleedsbutmoremajorgastrointestinalbleeding.

IntheARISTOTLE13trial,apixabanwasassociatedwithfewermajorbleeds,butmoregastrointestinalbleedsthanwarfarin.

Dyspepsia:wasmorecommonwithdabigatran150mgthanwarfarinbutwasnotlistedasanadverseeventwithrivaroxabanorapixaban.Drugswerediscontinuedin~20%ofpatientsat2yrs–similartothosestoppingwarfarin.PPIsmaybenecessaryfordyspepsia.

Totalmortalitywasreducedwithapixaban;3.52%peryearcomparedto3.94%peryearinthewarfaringroup(95%CI0.80–0.99,P=0.047).Non-significantreductionintotalmortalitywasfoundwithdabigatran150mgandrivaroxaban20mg.

13.Apixabanversuswarfarininpatientswithatrialfibrillation.GrangerCB,AlexanderJH,McMurrayJJ,etal.NEJM2011;365:981-92.

12 IMPROVING ANTICOAGULATION

NOAC evidence contd.

167peoplewouldneedtobetreatedwithapixabanand86withdabigatranratherthanwarfarinfor2yearstoavertonestroke.

Thecostofayear’streatmentwithanyofthethreenewagentsissimilarat£730-£780peryear.Thecostofwarfarinplusmonitoringis~£400.

Comparedtonotreatment,NOACarecost-effectivebutinpeopleonwarfarinwithgoodINRcontroltheyarenotcosteffectiveatcurrentprices14.However,inpeoplewithpoorINRcontroldespiteadherence,whoareathighriskofstroke(CHADS2≥3)NOACarelikelytobecost-effective.

Meta-analysisofallmajorNOACtrialsincomparisonwithwarfarinconfirmssignificantreductionsinstroke,intracranialhaemorrhage,andmortality,butincreasedgastrointestinalbleeding15.

Reversing anticoagulation

ThemajorconcernwithNOACsistheinabilitytorapidlyreverseamajorbleed.Theeffectsofwarfarincanberapidlyandeasilyreversed.However,thisisnotthecasewithNOACswhichhaveahalf-lifeof13-17hrsinolderpatients.

Thisisofconcerntohaematologistswhoregularlymanagebleedsinanticoagulatedpatientsandexperienceinacutesituationsislimited.Warfarinisthecommonestreasonforhospitaladmissionforadversedrugevents–almostentirelybleeding.

Thatbloodmonitoringisnotneededisanadvantage.However,inrealworldsettingstheabsenceofconstantremindersmayresultinlesssatisfactoryadherenceunlessregularreviewsareundertaken.Inwellcontrolledindividuals,monitoringwarfarin3monthlyisasgoodasmorefrequenttestingwhichfurtherreducestheadvantageofNOACinthisgroup.

14. MHRA guidance, dabigatran October 2011.15. Ruff CT, Giugliano RP, Braunwald E. Compar ison of the efficacy and safety of new oral anticoagulants with warfarin in patients with atrial fibrillation:a meta-analysis of randomised trials.Lancet 2014;383:955-62.

Renal function

SomeuncertaintyremainsoverdosageofNOACsinrenaldisease,thefrailelderlyorwithdrugssuchasamiodarone.PeoplewithpoorrenalfunctionshouldbeassessedusingtheCockcroft-Gaultestimateofrenalfunction.TheeGFRtendstogivehighervalues(atlowlevelsoffunction)andthusmayunderestimatetheextentofimpairedrenalfunction.IfeGFRisusedthenpatientswithpoorrenalfunctionmayreceiveaninapproriatelyhighdose.NOACsarenotrecommendedinpatientswithsevererenalorliverdiseaseandusewithamiodarone,azolessuchasketoconazole,quinidine,verapamilandrifampicinshouldbeavoided.

CumbriaNHShaveanexcellentwebsiteonNOACswww.cumbria.nhs.uk/ProfessionalZone/MedicinesManagement/Guidelines/Prescribing-Guidance-for-NOACs.pdf

MHRAguidanceadvisesassessmentofrenalfunctioninallpatientsstartingNOACswhenpoorrenalfunctionissuspectedandatleastannuallyinpatientsolderthan75orthosewithrenalimpairment.

TheCockcroftGaultcalculatorisavailableonthewebathttp://www.nuh.nhs.uk/nch/antibiotics/Renal%20impairment/clcrcalc.asp

New atrial devices

InembolusassociatedwithAF,theoriginin90%istheleftatrialappendage.Newdevicestoclosetheappendageareimplantedpercutaneouslyundergeneralanaesthetic.Inlargerandomisedtrialstheyhavebeenshowntoprovidesimilarefficacytowarfarinforstrokeprevention16.Theproceduredoeshaveanoperativeriskandthetechnologyhasonlybeenproveninonestudy.ThesedevicesarethereforerecommendedforpatientsathighriskofstrokeandwhoareunabletotakewarfarinorNOACs,specificallybecauseofhighriskofbleeding.

16. Holmes DR, et al. Lancet. 2009 374:534-42

IMPROVING ANTICOAGULATION 13

Warfarin start or switchCCGsandprescribingadvisorshavedetailedguidanceonstartingorswitchingtowarfarinandavarietyofwaysofmonitoringINRandclinicallyreviewingthepatient.

AsNOACsarerecentintroductionswehavesummarisedbelowthestepsfortheirinitiationandmonitoring

Starting NOAC or switching from antiplatelet or warfarin to NOAC Whenstartingorswitchingdiscussreasonsforthenewdrugwiththepatientandtherisksandbenefits.

•CheckALT&renalfunction•NOACdosebasedonage,weightandrenalfunction•Reviewmedicationsforpotentialinteractions•Wherepatienthasheartvalve,stentorothercardiacprocedureseekcardiologistadviceGivepatientprescriptionsopharmacistcanarrangesupply.

If switching from aspirin/clopidogrel, discontinue for 24 hours, then start the NOAC.

If switching from warfarin discontinue for 2 days, then start NOAC.

•ContactanticoagulantclinicandgetthemreadytocheckINRpriortochangeand2daysafterstoppingwarfarin.•ForapixabananddabigatrancommenceNOACifINR<2;forrivaroxabancommenceifINR<3•Give the patient an alert card and patient informa- tion leaflet for the NOAC. •Ensurepatient/carerssendremainingwarfarintopharmacy.•Ensurerecallfornextandannualreviewisontheclinicalsystem.CCGsmaydifferinwaysofmonitor-ingandsupportforadherencetoNOACs.

Patient advice on new anticoagulant

• Indication and duration of treatment

• Changed circumstanceWhattodoifnewdiagnosis,majorsurgery,immobilityorbleedingrisk.

• Compliance.Askpatienttobringmedicationtocheckremainingdoses.Emphasiseneedtoavoidmissingdosesasshorterhalf-lifethanwarfarin.Dosettebox;Smartphonereminderaids.

• Missed doses - see below

• Bleeding. Thisisthecommonestadverseeffectofanticoagulants.‘Nuisance’bleedingpreventivemeasurespossible?(cf.haemorrhoidectomy).

• Doesbleedingimpactonqualityoflife–?revisedose.Considerbleedingversusstrokerisk(CHA2DS2-VASc).CheckHb.

• When to seek medical attention.SymptomsTIA,stroke,pulmonaryembolism.Bleeding.

• Other side effects.Nauseaandgastrointestinalsideeffectsarerelativelycommon.RelationtoNOAC/warfarin–alternativeanticoagulant?

• Interacting medications? OTCmedicationorNSAID?

• Dental treatment or surgery arrangements.

Annually checkHb,renalfunctionandALT.6 monthlyifCrCl<60ml/min,age75yrs+ormultipleco-morbidityand3 monthly ifCrCl<30ml/min.

Alert cardMakesurepatientstillhasandcarriesalertcard.

Missed doses Dabigatranandapixabanaretakentwiceaday.Ifmissed,takeitassoonasrememberedbutomitdoseiflessthan6hourstothenextdose.Donottakeadoubledosetomakeupformisseddoses.

Rivaroxabanisoncedaily.Ifmissedtakeitassoonasremembered.Donottakemorethanonetabletinasingledaytomakeupforamisseddose.Carryononcedailyasusualthefollowingday.

CCGs currently recommend initiating anticoagulation in specialist clinics

14 IMPROVING ANTICOAGULATION

Alert cards

PatientalertcardsfortheindividualNOACsareavail-abletoorderinthefollowingway:

Rivaroxaban(Xarelto®)(Bayerplc)ContacttheMedicinesInformationDepartmentTel:01895523740

Dabigatran(Pradaxa®)BoehringerIngelheimLtd)Orderdirectlyfromwebsite:http://www.pradaxa.co.uk/hcp/spaf/education-al-pack-uk.php

Apixaban(Eliquis®)(Bristol-MyersSquibb-Pfizer)ContacttheMedicinesInformationDepartmentTel:01895523740

NHS Medicines management guidance

Moredetailedguidnceonwafarinandnewanti-coagulantsisavaialablefromtheNHSmedicinesmanagementwebsitesinthelocalareas.

NorthCentralhttp://ncl-jfc.org.uk/noac-prescrib-ing-guides.html

SimilarguidanceisavailablefromtheNELondonMedicineManagamentsGroup.

blizard.qmul.ac.uk/ceg-resource-library.html

Centre for Primary Care and Public HealthBarts and The London School of Medicine and DentistryYvonne Carter Building58 Turner StreetLondon E1 2ABTel: 020 7882 2553 Fax: 020 7882 2522email: ihse-ceg-admin@qmul.ac.ukwebsite: blizard.qmul.ac.uk/ceg-resource-library.html