atrial fibrillation: a london approachpsnc.org.uk/.../2017/12/city-hackney-lpc-slideset.pdf · 10,...
TRANSCRIPT
13/12/17
1
ATRIALFIBRILLATION:ALondonapproach
• Whyischangenecessary?• Whatwillchangeachieve?• Howwillchangebedelivered?
So:risAntoniou,ConsultantPharmacist,CardiovascularOnbehalfofPanLondonPrimaryCareAFImprovementProgramme12thDec2017
Aims
• Describethekeypriori<esofPanLondonAFprogramme• RelatetheperformanceofCity&HackneytoPanLondonAFprogramme
• Listthekeyperformanceindicatorsset• Describeanddifferen<atethepharmacologicalac<onsof
availableoralan<coagulants• Listtheopportuni<esforyoutoimprovethemanagementofpeoplewithatrialfibrilla<onaspartofDETECT,PROTECTandPERFECTadherencetoimproveoutcomes
13/12/17
2
AtrialFibrilla<on
Abriefintroduc<on
13/12/17
3
TheImpactofAFonStrokeOutcomes
� SurvivalispoorerandstrokerecurrenceratesarehigherfollowingAF-relatedstroke
AF=atrialfibrillation;OR=oddsratio;CI=confidenceinterval1.LinHJ,etal.Stroke1996;27:1760–4;2.DulliDA,etal.Neuroepidemiology2003;22:118–23
AF patients (n=30)
Non-AF patients (n=120)
1-year post stroke recurrence 23% 8%
30-day post stroke mortality 30% 17%
1-year post stroke mortality 63% 34%
Framingham(10-yearfollowupfrom1981)
13/12/17
4
HartRGetal.AnnInternMed.2007;146:857-867
Study Year AFASAK I 1989; 1990 SPAF I 1991 EAFT 1993 ESPS II 1997 LASAF 1997
Daily Alternate day
UK-TIA 300 mg daily 1200 mg daily
1999
JAST 2006
Aspirin trials (n=7)
Antiplatelet agents cf placebo/control Relative Risk Reduction (95% CI)
Favors Antiplatelet Favors Placebo or Control
100% 50% 0 -50% -100%
EfficacyofAspirinComparedWithPlacebo
Randomeffectsmodel;Errorbars=95%CI;*p>0.2forhomogeneity; †RelaFveriskreducFon(RRR)forallstrokes(ischaemicandhaemorrhagic)HartRGetal.AnnInternMed2007;146:857–67.
Warfarinbe]er Placebobe]er
RRR(%)†100 –100 50 0 –50
AFASAK
SPAF
BAATAF
CAFA
SPINAF
EAFT
All trials RRR64%*,ARR2.7%(95%CI:49–74%)
AspirinRRR19%0.7%ARR
EfficacyofWarfarinforStrokeReduc<onComparedWithPlaceboorControlinSixStudies
13/12/17
5
So why the poor prescribing rates of anticoagulation?
13/12/17
6
Physician Concerns About Warfarin for Stroke Prevention in AF
0
20
40
60
80
Risk of Fall History of GI Bleed
History of Non-CNS Bleed
History of CV Hemorrhage
Risk vs benefit of warfarin § 47% benefit greatly outweigh risk § 34% risk slightly outweigh benefit § 19% risk outweigh benefit
Perc
ent
MoneSeetal.JAmGeriatrSoc.1997;45:1060-1065.
Pa:entConcernsAboutAF
0
25
50
75
100
Stroke Death Major Bleeding
Inconvenience Minor Side Effects Cost
Man-Son-Hing et al. Arch Intern Med. 1996;156:1841-1848.
Perce
nt
91%
38%
13% 9% 2% 5%
13/12/17
7
CowanC,etalHeart2013;0:1-7
Older AF patients less likely to get warfarin
Falls–whatistherisk?
• Markov decision analytic model was used to determine the preferred treatment strategy in patients > 65 yrs/old
• Patients need to fall >295 times per year for risk to outweigh benefit
• Mean number of falls / year of elderly people who fall: 1.8
Man-Son-HingetalArchInternMed.1999;159:677-685
13/12/17
8
From: Risk of Thromboembolism, Recurrent Hemorrhage, and Death After Warfarin Therapy Interruption for Gastrointestinal Tract BleedingArch Intern Med. 2012;172(19):1484-1491. doi:10.1001/archinternmed.2012.4261
Figure. Time-to-outcome analysis according to resuming warfarin therapy status. A, Thrombosis (P = .002, log-rank test); B, recurrent gastrointestinal tract bleeding (GIB) (P = .10, log-rank test); C, death (P < .001, log-rank test); and D, death including only patients who died at least 7 days after the index GIB (P < .001, log-rank test).
Birmingham Atrial Fibrillation Treatment of the Aged
• 2001-2004;260GPsinEnglandandWales• 973pts≥75years(81.5±4.2)• 72%CHADS2≤2• 40%onwarfarin,42%onaspirin• Warfarin(targetINR2–3)oraspirin(75mgper
day)• 10endpoint-fatalordisablingstroke(ischaemic
orhaemo-rrhagic),otherintracranialhaemorrhage,orclinicallysignificantarterialembolism
BAFTA:
RR=0.48(0.28–0.80)p=0.0027
0 1 2 3 4 5 6
Aspirin Warfarin
Years after randomization
Even
t fre
e su
rviv
al
100
75
50
25
0
Mant J, et al. Lancet 2007;370:493-503
24 (1.8%)
48 (3.8%)
Intra-cranial haemorrhage on W vs A: 0.5% vs 0.4% (RR 1.15, 0.29 – 4.77, n.s.)
Extra-cranial haemorrhage: 1.4% vs 1.6% (RR 0.87, 043 – 1.73, n.s.)
INR > 3.0 14% of the time
Stroke: 0.8% vs 1.8% RR = 0.30 (0.13-0.63) p = 0.0004
13/12/17
9
Riskstra<fica<on
Think of a patient……. (1)
� 87yearoldmale� Irregularpulse AFconfirmed
onECG� RelevantPMH
� Hypertension
� Howdoweknowifheisatrisk....?
13/12/17
10
CHADS2 criteria Score
Congestive heart failure 1
Hypertension 1
Age >75 yrs 1
Diabetes mellitus 1
Stroke / transient ischaemic attack
2
1 Gage BF et al. JAMA 2001;285:2864–70. 2 Based on data from Gage BF et al. JAMA 2001;285:2864–70.
0
4
8
12
16
20
0 1 2 3 4 5 6
CHADS2 score
Adjusted stroke risk
NRA
F a
dju
ste
d s
tro
ke ra
te
pe
r 100
pa
tient
ye
ars
, with
out
asp
irin
Score 0-1 low risk - use aspirin Score ≥2 moderate risk – consider warfarin
HowdoIrisk-assessAFpa<entssimply?StrokeriskassessmentwithCHADS2
StrokeriskassessmentwithCHA2DS2-VAScCHA2DS2-VASc criteria Score Congestive heart failure/ left ventricular dysfunction
1
Hypertension 1 Age ≥75 yrs 2 Diabetes mellitus 1 Stroke/transient ischaemic attack/TE 2
Vascular disease (prior myocardial infarction, peripheral artery disease or aortic plaque)
1
Age 65–74 yrs 1 Sex category (i.e. female gender)
1
CHA2DS2-VASc total score
Rate of stroke/other TE (%/year)*
0 0.0
1 1.3
2 2.2
3 3.2
4 4.0
5 6.7
6 9.8
7 9.6
8 6.7
9 15.2
*Theore:calrateswithouttherapy:assumingthatwarfarinprovidesa64%rela:vereduc:onin TErisk(2.7%ARR),basedonHartetal.
1LipGYHetal.Stroke2010;41:2731–2738.2HartRGetal.AnnInternMed2007;146:857–67.
TE=thromboembolism
PeoplewithCHADS2risk0or1canhaveaCHA2DS2-VASc=3
13/12/17
11
For our patient……
87yearoldmanwithhypertension
An<coagulate!
Think of a patient….. (2)
� 66yearoldBri<shwoman,newlyregisteredpa<entü AF(2009)onwarfarinü Hypertension
13/12/17
12
Refining risk assessment
So,whattodohere?
An<coagulate!
• AF is a major risk factor for stroke (five-fold increased risk).
• AF is a contributing factor in 1 in 5 strokes. o More severe o Higher mortality o More likely to require long-term nursing care
• Treatment with anticoagulation reduces the risk of AF-related stroke by approximately two-thirds.
BUT
Only 69% of high risk AF patients are anticoagulated (QOF 2013/14).
Only 41% of patients known to have AF presenting with a new stroke are anticoagulated (SSNAP 2014/15).
Atrialfibrilla:onandstrokeNa:onalperspec:ve
13/12/17
13
TopreventAF-relatedstrokeandassociatedmortalitythroughbe]eriden<fica<onandmanagementofpeoplewithatrialfibrilla<on
VisionforLondon
Increasingan<coagula<onofuntreatedhighriskAFpa<ents
Improvingthequalityofan<coagula<on
Increasingthedetec<onofundiagnosedAFinhighriskpa<ents
MeasurableOutcomes
AGREEDAFQUALITYSTANDARDS• Propor<onofpa<entswithaCHA2DS2VAScscore≥2onan<coagula<ontreatment:aim>80%(noexcep<ons)• Propor<onofpa<entswithaCHA2DS2VAScscore≥2onan<-platelettreatment:aim<10%(noexcep<ons)• Propor<onofpa<entstakingwarfarinwithaTTR<65%whohavetheiran<coagula<onqualityreassessedatleast
onceeverysixmonths–aim=100%
• Propor<onofpa<entsover65whohaveapulsecheck(manualorothertechnology)over5years–aim>90%
SYSTEMLEVELIMPACTMEASUREMENT• Numbersofpa<entswhodiedasaconsequenceofastroke
• NumberofAF-relatedstrokeepisodes
13/12/17
14
• Detecto Awarenesscampaignso PulseCheckso Detec<ondevices
• Protecto Increasean<coagula<on(decreaseaspirin)o Ini<atean<coagula<oninprimarycareo (heartrateandrhythmcontrol)
• Perfecto An<coagula<onqualityo Self-monitoringandmanagemento OACsadherence
WhatdoesthismeanforCity&HackneyCCG?
28
366
13/12/17
15
Protect%Ratesofan:coagula:oninhighriskAFpa:ents(CHADSVASc>1)andnumberofuntreatedhighriskpa:entswithinCity&HackneyCCG(QoF2016/17)
Howcanweimprovean<coagula<on?
13/12/17
16
Na<onalIns<tuteofHealthCareExcellence(NICE)ClinicalGuideline180.Atrialfibrilla<on:themanagementofatrialfibrilla<on.June2014;Na<onalIns<tuteofHealthCareExcellence(NICE)ClinicalGuideline180.Atrialfibrilla<on:themanagementofatrialfibrilla<on–methods,evidenceandrecommenda<ons.June2014
Poorcontrol
Lowrisk
Assessbleedingriskstra<fica<onusingHAS-BLED
Discussrisksandbenefitsofan<coagula<on
Iden<fylowriskpa<entsi.e.CHA2DS2-VASc=0(men)or1(women)
CHA2DS2-VASc=1(inmen)Consideroralan<coagulant
CHA2DS2-VASc≥2Offeroralan<coagulant
Discusstheop<onsforan<coagula<onwiththepersonandbasethechoiceontheirclinicalfeaturesandpreferences
VitaminKantagonist(VKA) Non-VKAoralan<coagulant(NOAC)(dabigatran,apixaban,rivaroxaban)
Peoplewhochoosenottohavetreatment
Noan<-thrombo<ctherapy
Lesatrialappendageocclusion
Assessan<coagula<oncontrolNon-VKAoralan<coagulant(NOAC)(dabigatran,apixaban,rivaroxaban)
Annualreviewforallpa<ents
Non-VKAcontraindicatedor
nottolerated
An<coagula<oncontraindicated
Assessstrokeriskstra<fica<onusingCHA2DS2-VASc
2014NICEAFguidelineforstrokepreven<on:firstupdatesince2006
Warfarin § Most commonly used anticoagulant
worldwide § Highly effective oral anticoagulant § But it has its limitations….
13/12/17
17
Warfarinanditschallengingtherapeu:cwindow
ACC/AHA/ESCguidelines:FusterVetal.CirculaFon2006;114:e257–e354.
1Interna:onalnormalizedra:o(INR)
Odd
sra:
o
2
15
8
10
5
01
3 4 5 6 7
Intracranialbleed
Therapeu:crange
20Requiresdoseadjustmentandregularmonitoring
Ischaemicstroke
Why<meintherapeu<crange(TTR)ma]ers
0 500 1000 1500
Survivaltostroke(days)
0.6
0.7
0.8
0.9
1.0
Cumula:
vesu
rvival 71–100%
Warfaringroup
61–70%51–60%41–50%31–40%<30%Nonwarfarin
MorganCLetal.ThrombosisResearch2009;124:37–41.
13/12/17
18
NICE Guideline for AF (June 2014)
• ReviewTTRateachvisit(exclude1st6weeksandmustbeoveraperiodof≥6/12):– Reassessifoverthepast6months
• x2INRs>5orx1INR>8orx2INRs<1.5• TTR<65%
• Trytocorrectandtakeintoaccountreasonsforpoorcontrol:– Cogni<vefunc<on– Adherence– Illness– Interac<ngdrugRx– LifestyleincdietandEtOH
• Ifcannotbeimprovedconsiderotherstrategies
Featuresofnoveloralan<coagulants
*Ofabsorbedsubstance;#OfgivensubstanceBCRP=breastcancerresistanceprotein;CYP=cytochromeP450;P-gp=P-glycoprotein1.Erikssonetal.ClinPharmacokinet2009;48:1–22;2.Xarelto[packageinsert].Titusville,NJ:JanssenPharmaceu<cals,Inc.;2011;3.ELIQUISSummaryofProductCharacteris<cs.BristolMyersSquibb/PfizerEEIG,UK;4.Ruffetal.HotTopicsinCardiology2009;18:1–32;5.Matsushimaetal.ClinPharmacolDrugDev2013;2:358–366;6.Matsushimaetal.AmAssocPharmSci2011;abstract;7.Ogataetal.JClinPharmacol2010;50:743–753;8.EdoxabanSummaryofProductCharacteris<cs(SmPC)2015;9.Gonzalez-Quesada&Giugliano.AmJCardiovascDrugs2014;14:111–127
Dabigatran1 Rivaroxaban1,2 Apixaban1,3 Edoxaban4-9
Target IIa(thrombin) Xa Xa Xa
HourstoCmax 1.25–3 2–4 3–4 1–2
CYPmetabolism None 32% ~25% <10%
Bioavailability 6% 80% 60% 62%
Transporters P-gp P-gp/BCRP P-gp/BCRP P-gp
Proteinbinding 35% 93% 87% 50%
Half-life 14–17h 7–11h 8–15h 10–14h
Renalelimina<on 80%* 33%# 27%# 50%*
Administra<on BD OD BD OD
13/12/17
19
PhaseIIIAFtrials:Baselinecharacteris<cs
1.Connollyetal.NEnglJMed2009;361:1139–1151;2.Pateletal.NEnglJMed2011;365:883–891;3.Grangeretal.NEnglJMed2011;365:981–992;4.Giuglianoetal.NEnglJMed2013;369:2093–2104
RE-LY1 ROCKET-AF2 ARISTOTLE3 ENGAGEAF4
Drug Dabigatran Rivaroxaban Apixaban Edoxaban
Enrolled 18,113 14,264 18,201 21,105
Age (yrs) 72 ± 9 73 [65-78] 70 [63-76] 72 [64-77]
Female 36% 40% 35% 38%
CHADS2 score ≥3 32% 87% 30% 52%
VKA naive 50% 38% 43% 41%
Paroxysmal AF 33% 18% 15% 25%
Prior stroke/TIA 20% 55%** 19% 18% / 12%
Diabetes 23% 40% 25% 36%
Prior CHF 32% 62% 35% 56%
Hypertension 79% 91% 87% 90%
**includes prior systemic embolism !!!Directcomparisonsimpossibleduetoselec:onbiasanddifferencesindesign!!!
Rela<verisk(95%CI) NOACevents WarfarineventsStudyRela<verisk(95%CI)
RE-LY(dabigatran)* 0.66(0.53–0.82)P=0.0001 134/6,076 199/6,022
ROCKETAF(rivaroxaban)† 0.88(0.75–1.03)P=0.12 269/7,081 306/7,090
ARISTOTLE(apixaban)‡ 0.80(0.67–0.95)P=0.012 212/9,120 265/9,081
ENGAGEAF-TIMI48(edoxaban)§ 0.88(0.75–1.02)P=0.10 296/7,035 337/7,036
Combined# 0.81(0.73–0.91)P<0.0001 911/29,312 1107/29,229
Compara<veefficacyofNOACsandwarfarin:Strokeorsystemicembolicevents
Datafromtheintent-to-treatpopula<on*Dabigatran150mgtwice-daily;†rivaroxaban20mgonce-daily;‡apixaban5mgtwice-daily;§Edoxaban60mgonce-dailyregimen(includespa<ent-specificdosereduc<ontoedoxaban30mgonce-daily)CI=confidenceinterval;NOAC=non-vitaminKantagonistan<coagulantRuffCTetal.Lancet2014;383:955–962
0.5 1.0 1.5
FavoursNOAC Favourswarfarin
13/12/17
20
Secondaryefficacyoutcomes:PooledNOACsversuspooledwarfarin
Treatmentarmsanalysed:Dabigatran150mgtwice-daily;rivaroxaban20mgonce-daily;apixaban5mgtwice-daily;edoxaban60mgonce-dailyregimen(includespa<ent-specificdosereduc<ontoedoxaban30mgonce-daily)CI=confidenceinterval;NOAC=non-vitaminKantagonistan<coagulantRuffCTetal.Lancet2014;383:955–962
Rela<verisk(95%CI) NOACevents WarfarineventsOutcomeRela<verisk(95%CI)
Ischaemicstroke 0.92(0.83–1.02)P=0.10 665/29,292 724/29,221
Haemorrhagicstroke
0.49(0.38–0.64)P<0.0001 130/29,292 263/29,221
Myocardialinfarc<on
0.97(0.78–1.20)P=0.77 413/29,292 432/29,221
All-causemortality 0.90(0.85–0.95)P=0.0003 2,022/29,292 2245/29,221
0.5 1.0 1.5
FavoursNOAC Favourswarfarin
Rela<verisk(95%CI)NOACevents WarfarineventsOutcome
Rela<verisk(95%CI)
Intracranialhaemorrhage
0.48(0.39–0.59)P<0.0001 204/29,287 425/29,211
Gastrointes<nalbleeding
1.25(1.01–1.55)P=0.043 751/29,287 591/29,211
Secondarysafetyoutcomes:PooledNOACsversuspooledwarfarin
Treatmentarmsanalysed:Dabigatran150mgtwice-daily;rivaroxaban20mgonce-daily;apixaban5mgtwice-daily;edoxaban60mgonce-dailyregimen(includespa<ent-specificdosereduc<ontoedoxaban30mgonce-daily)CI=confidenceinterval;NOAC=non-vitaminKantagonistan<coagulantRuffCTetal.Lancet2014;383:955–962
0.0 1.0 2.01.50.5
FavoursNOAC Favourswarfarin
13/12/17
21
<15ml/min
Notrecommended
Pa<enthasriskfactorforstroke
Es<mateCrCl
15–49ml/min*
15mgod
≥50ml/min
20mgod
Rivaroxaban
2.5mgbid 2.5mgbid 5mgbid
Apixaban
Pa<enthasriskfactorforstroke
Es<mateCrCl
<15ml/min 15–29ml/min ≥30ml/min
Checkage Checkweight Checkserumcrea<nine
≥80years ≤60kg ≥133µmol/l
If≥2features if≤1features
Notrecommended
EdoxabanPa<enthasriskfactorforstroke
Es<mateCrCl
<15ml/min 15–50ml/min >50ml/min
Notrecommended 30mgod
30mgod 30mgod
60mgod
≤60kg PotentP-gpinhibitors
1.RivaroxabanSmPC;2.ApixabanSmPC;3.DabigatranSmPC;4.EdoxabanSmPC
Pa<enthasriskfactorforstroke
Es<mateCrCl
<30ml/min 30–50ml/min >50ml/min
Age>80years
Age<75years
Age75–80years
Age>80years
Contraindicated
Lowthromboembolicriskandhighbleedingrisk
110mgbid
110mgbid
150mgbid
150mgbid
110mgbid
150mgbid
110mgbid
Dabigatran
Age≥75yearsorhighriskofbleeding
ABCDruleDoseAdjustmentsinNVAF
Maximisingadherence
13/12/17
22
NewMedicineService(NMS)
Improveadherence10%
13/12/17
23
pharmacist confidence and experience with vitamin K antagonists
HamediN,….AntoniouS.IntJClinPharm2017
PharmacistconfidenceandexperiencewithNon-vitaminKantagonistOralAn<coagulants(NOACs)
HamediN,….AntoniouS.IntJClinPharm2017
13/12/17
24
ResourcesaccessedwhenundertakingNMS
Resource Numberofpharmacists
Na:onalBri:shFormulary(BNF) 66%(87/131)
Internet 35%(44/131)
SummaryofProductCharacteris:cs(SPC)and/orPa:entInforma:onLeaflet(PIL)18%(23/131)
An:coagulantresources 10%(13/131)
NewMedicineServiceandorMedicineUseReviewresources 7%(9/131)
Ar:cles 7%(9/131)
Na:onalPharmacyAssocia:onNMSresources 4%(5/131)
StandardOpera:ngProcedureorguidelineonNMS 2%(3/131)
Other 8%(10/131)
HamediN,….AntoniouS.IntJClinPharm2017
13/12/17
25
Atrialfibrilla:oninEngland
• 1.4millionpeopleinEnglandarees<matedtohaveAF
(prevalence2.4%)
• Almost900,000recordedAFcases(prevalence1.6%)
• Overathirdareundiagnosed888,926
1,363,321
474,395
0
200,000
400,000
600,000
800,000
1,000,000
1,200,000
1,400,000
QOF2013/14 NCVIN UndiagnosedAF
Detect-LondonAFprevalence
0.00
0.20
0.40
0.60
0.80
1.00
1.20
1.40
1.60
1.80
AFprevalence(%)QOF2013/14
Londonaverage=0.92%
England=1.57%
13/12/17
26
0.0
0.5
1.0
1.5
2.0
2.5
3.0
ExpectedPrevalence
QOFPrevalence2013/14
AFexpectedvsQOFprevalence2013/14 England2.4vs1.6%
London1.7vs0.9%City&H1.2vs0.6%
NCVIN–AFprevalence,yhpho.org.uk
Detect–Londonshorrall
Whatabouttheroleforpharmacy?
13/12/17
27
J
J
DETECT
:Findingm
oreAF
-De
vices
Non12-LeadECG
Smartphoneapplica<on
BloodPressuremonitors
ALIVECOR(Kardia™MobileandKardiaApp)
13/12/17
28
ATRIALFIBRILLATION:ALondonapproach
• Whyischangenecessary?• Whatwillchangeachieve?• Howwillchangebedelivered?
So:risAntoniou,ConsultantPharmacist,CardiovascularOnbehalfofPanLondonPrimaryCareAFImprovementProgramme12thDec2017