PRESENTATION TITLE Case Studies

1) SH is a 67 year old male. He has a history of type 2 diabetes, controlled hypertension and peripheral artery disease. He takes naproxen 500mg bd for arthritis and admits to drinking 4-5 cans per night. He develops AF and a rate control strategy is adopted with bisoprolol and digoxin.

a) What is his stroke risk and bleeding risk? b) Should he be offered thromboprophylaxis? c) Which agent would you recommend?

d) If using warfarin, how would you define poor anticoagulant control?

e) He says he does not want warfarin as his mum is on it and it is too much trouble. What would you do?

f) If you were to start a NOAC, what discussion points would you want to raise with the patient?

g) If initial treatment was with warfarin: after 3 months he develops significant hair loss. What would you do?

2) AG is a 49 year old female who presents with AF. She has no history of hypertension, diabetes, stroke or TIA, IHD, PAD and her echo shows good LV function.

a) What is her annual stroke risk b) Should she be offered

thromboprophylaxis?

3) DT is a 85 year old female with a previous history of heart failure and diabetes. Her eGFR is around 28ml/min. She develops AF.

a) Would you initiate thromboprophylaxis? b) If so, which agent would you start?

4) CD is a 47 year old women with a history of recurrent PE. She is currently managed with long term dalteparin 15000 units daily as part of a shared care protocol.

a) Would you consider a NOAC for the management of this patient?

b) If so, which agent would be appropriate and at what dose?

c) Who should make the change?

AF and Stroke • AF increases risk of stroke. Risk increases

further with age • 1.5% increase in 50-59 year olds • 23.5% increase in 80-89 year olds

• AF causes more severe strokes • 30 day mortality 25% vs 14% • At 12 months 30% vs 10.9% severely dependant

• ALL patients with a history of AF should be risk

assessed for stroke and appropriate antithrombotic therapy initiated

CHADS2 Score • 1 point each for congestive heart failure,

hypertension, age>75 and diabetes. 2 points for previous stroke or TIA

• Score ranges from 0-6. Stroke risk increases as score increases (distribution –NHS Improvement)

– 0 = 1.9% (15%) 3 = 5.9% (15%) 6 = 18.2% (1%) – 1 = 2.8% (26%) 4 = 8.5% (9%) – 2 = 4.0% (30%) 5 = 12.5% (3%)

CHA2DS2Vasc • Refined version of scoring system proposed

– 1 point each for • Heart failure • Hypertension • Diabetes • Vascular disease • Female

– 2 points for previous stroke or TIA – 1 point for age 65-74, 2 points if 75 or over

• Better prediction of low risk

HAS-BLED • Uncontrolled Hypertension 1 • Abnormal renal and liver function 1 or 2 • Stroke 1 • Bleeding 1 • Labile INR 1 • Elderly (>65 years) 1 • Drugs or alcohol 1 or 2 0-2=low bleeding risk (< 2%) >3=high bleeding risk (3.7-12.5%)

Warfarin for Stroke Prevention

Lip G et al. BMJ 2002;325: 1022-1025

Issues with warfarin • Warfarin is a good drug if INR maintained in range • TTR used to determine level of control • Variable time in therapeutic range

– SPAF studies vary between 42%-71% – Sub therapeutic INR increases the risk of stroke – Excessive INR increases bleeding risk

• Unpredictable effect • Drug interactions • Monitoring requirements • Patient selection and education

Older patients are less likely to get warfarin

Younger

Older

Gallagher AM et al. J Thromb & Haem 2008;6:1500-1506

Why don’t elderly patients get warfarin?

• Fear of bleeding risk • Falls • Anaemia • Previous bleeds • Concomitant antiplatelet therapy • Too many other drugs

Antiplatelet therapy

• Aspirin reduces stroke risk by 22% • Warfarin is more effective than aspirin alone

(BAFTA study 1.8% yearly risk vs 3.8%) • Warfarin is more effective than aspirin plus

clopidogrel (ACTIVE W trial 1.4%/year vs 2.4%/year)

• Aspirin and clopidogrel is more effective than aspirin alone but results in more bleeding (ACTIVE A 2.4%/year vs 3.3%/year)

Dabigatran Direct thrombin inhibitor • RE-LY study - open label, CHADS2 >1 • 110mg bd as good as warfarin with fewer major

bleeds • 150mg bd reduced end points of stroke and

systemic embolism and ischaemic stroke but not mortality compared with warfarin with similar major bleeds

• Dabigatran had a higher incidence of dyspepsia and GI bleeding compared to warfarin

Dose 150mg bd is the usual dose Reduce to 110mg bd if: • over 80 • On verapamil • If bleeding risk high Contraindicated if CrCl <30ml/min Monitoring • Renal function before starting in all and at least

annually if over 75 Reversal • No specific reversal agent yet

Interactions • Contraindicated with ketoconazole,

itraconazole, ciclosporin and tacrolimus

NICE recommendations • Consider as treatment option in licensed

patients • Decision to use made after full and

informed discussion with patient • Decision to switch from warfarin based on

INR control

Rivaroxaban Direct Factor Xa inhibitor • ROCKET AF study – double blind, Sham control,

CHADS2 >3 or stroke/TIA • Rivaroxaban 20mg od • Non-inferior to warfarin (only superior in on-

treatment analysis for stroke and systemic emboli)

• No reduction in ischaemic stroke • No reduction in mortality • Similar overall bleeding risk (less ICH and fatal

bleeding) NEJM 2011; 365: 883-891

Dose 20mg od is normal dose Reduce dose to 15mg od if CrCl 15-49ml/min Reversal No specific reversal agent yet Interactions • Contraindicated with azole antifungals (except

fluconazole) and HIV protease inhibitors • Caution with rifampicin, phenytoin,

phenobarbitone and carbamazepine

NICE Recommendations • Consider as treatment option in licensed

patients • Decision to use made after full and

informed discussion with patient • Decision to switch from warfarin based on

INR control

Apixaban • ARISTOTLE – double blind sham control, CHADS2 >1 • Apixaban 5mg bd • Superior to warfarin for stroke and systemic emboli,

reduction in all cause mortality and reduction in major bleeding

• No reduction in ischaemic stroke NEJM 2011; 365: 981-992

• AVERROES – compared apixaban and aspirin in patients unsuitable for warfarin

• Apixaban reduced stroke and systemic emboli with no increase in major bleeding or ICH

NEJM 2011; 364: 806-817

Interpretation of NICE • What is a treatment option?

– Should be available for a patient who meets the clinical criteria in the guidance

– NHS must provide funding when a clinician concludes and the patient agrees that the recommended technology is the most appropriate to use

– ALL NICE approved TAs should be included in local formularies

– Once on formularies there should be no further barriers to their use or prescription

Local Implementation CMCN AF Task Group

– Staggered implementation of NICE 1st priority • Identify AF patients with CHADSVasc >1 not on

any thromboprophylaxis and start anticoagulant 2nd priority • Identify AF patients with CHADSVasc >1 on

aspirin and switch to oral anticoagulant if no C/I

• Patients who are well controlled on warfarin (TTR >67%), little or no benefit from changing to a NOAC

• NOACS are not suitable alternatives in patients at high risk of bleeding or with poor compliance

Consider NOAC if: – Warfarin control is poor (2 or more unexplained INR

values >5.0 or <1.7 in a 12 month period) – Significant problems with monitoring or taking warfarin – Patient clearly expresses a desire not to take warfarin

following an informed discussion

Pan Mersey APC (formerly NMMMC) • 1st priority is to identify AF patients on

aspirin or no thromboprophylaxis with a CHADS score >1 and initiate anticoagulants if no C/I

• Warfarin remains 1st line for SPAF and a trial of at least 6 months should be given to establish the degree of INR control

• Dabigatran, rivaroxaban and apixaban approved as green drug in certain patients

• Currently under review

• Green status means can be initiated by GP or hospital prescriber if: – Warfarin control is poor (TTR<67% or 2 or

more unexplained INR values >5.0 or < 1.7 in a 12 month period

or – Warfarin is unsuitable due to contraindication

or intolerance

Cost Implications • For patients with CHADS2 > 1 Patient Population Overall Annual Cost (£) (Excess Cost) Liverpool Sefton ALL Eligible AF 5M (1.78M) 2.9M (1M) All new AF 350K (317K) 203K (183K) TTR< 50% 840K (472K) 484K (273K) TTR < 65% 1.9M (1M) 1.1M (613K)

Warfarin C/I 939K 541K

Practicalities of Implementing Guidance

• How will asymptomatic/undiagnosed AF patients be identified?

• Who will review known AF patients on aspirin or no thromboprophylaxis?

• For patients on Warfarin, who monitors INR control? • Who is responsible for reviewing level of control? • Once poor control has been identified, who switches from

warfarin to NOAC? • Who informs the anticoagulant service that the patient is

no longer taking warfarin? • When switching allow INR to fall to around 2.0

New QOF Indicators for AF 2012/13

• AF5 - % of patients with AF in whom stroke risk assessed using CHADS2 in preceding 15 months

• AF6 - % of patients with a CHADS2 score of 1 treated with anticoagulant or antiplatelet therapy

• AF7 - % of patients with CHADS2 score > 1 currently treated with anticoagulant therapy