dr mammen ninan gpwsi in cardiology - home - the … · af affects up to 835,000 people in england...

Dr Mammen NinanGPwSI in Cardiology

AF affects up to 835,000 people in England alone and is expected to rise year after year.

AF is a known risk factor for stroke, the 3 rd highest cause of mortality in the UK and costs the NHS £ 2.8 billion per year

The Sent inel Stroke Nat ional Audit programme (SSNAP) found in August 2013 that only 36% of pat ients admit ted with stroke were on ant icoagulants.

It is est imated that 12500 strokes per year are related to AF and AF increases the risk of stroke by 5 – 6 t imes

It is est imated that 7100 strokes per year can be prevented if everyone with AF was appropriately managed

Manual pulse check Confirmed by ECG

Paroxysmal (Recurrent) Terminates spontaneously within 7 days and usually < 48hrs

Persistent (Recurrent)Lasts > 7 days. Not self terminat ing, requires electrical or pharmacological conversion

Permanent (Established)No further cardioversion attempts

Control of rate and/ or rhythm

Reducing the risk of stroke associated with AF

Incorporat ing the latest evidence and NICE guidance

◦ Do not use Aspirin as monotherapy for stroke prevention◦ Improving patient understanding and involvement i.e shared decision

making◦ Use of CHA2DSVASc score rather than CHAS2 score

1. Beta–blocker or rate–limit ing CCB as init ial monotherapy2. Digox in monotherapy with non- paroxysmal AF only if

individual is sedentary or takes lit t le exercise3. If pat ient st ill symptomatic or poor ventricular rate control

combine 2 out of beta- blocker, dilt iazem, digoxin

4. Do not px amiodarone for long- term rate control

If AF has reversible cause With HF thought to be primarily caused by AF New onset AF Atrial Flutter that might be eligible for ablat ion For whom rhythm control would be more suitable

Consider pharmacological and/ or electrical rhythm control when symptoms cont inue after HR has been controlled or for whom rate control has not been successful

Long- term rhythm control Beta- blocker – 1st line Dronedarone an opt ion for maintaining SR following

successful cardioversion Amiodarone for people with LV impairment or HF Not Flecainide or Propafenone in IHD or structural heart

disease

Refer people promptly at any stage if t reatment fails to control their symptoms and more specialised management is needed ……..4/ 52

Congest ive Heart Failure/ LVD 1 1 0.6- 2.0%

Hypertension 1 2 2.2- 3.7%

Age ≥ 75 years 2 3 3.2- 5.9%

Diabetes mellitus 1 4 4.8- 9.3%

Stroke/ TIA/ TE 2 5 7.2- 15.3%

Vascular disease (previous MI, PAD or aort ic plaque) 1 6 9.7- 19.7%

Age between 65 and 74 years 1 7 11.2- 21.5%

Sc - Sex category - Female 1 8 10.8- 22.4%

HIGH risk = a score of 2 or more (ant ithrombot ic therapy)

Score of 1 recommends ant icoagulant therapy in males..

Consider a risk of bleeding assessment such as the HAS- BLED score before ant icoagulat ion.

Hypertension (Systolic ≥ 160mmHg) 1 Abnormal renal/ liver funct ion 1or2 Stroke in past 1 Bleeding tendency or predisposit ion 1 Labile INRs 1 Elderly (≥ 65yrs) 1 Drugs (aspirin or NSAIDS) or alcohol 1or2

A score of 3 or more indicates increased one year bleed risk on ant icoagulat ion suff icient to just ify caut ion or more regular review.

Warfarin and NOACs have shown signif icant and consistent stroke risk reduct ion

For most pat ients benefit of OAC therapy outweighs bleeding risk For those with increased risk of bleeding – monitor bleeding risk Do not withold OAC therapy solely because of risk of falls! Do not offer OAC therapy to people < 65 & no risk factors other

than gender Consider for men with CHA2DS2- VASc of 1 Otherwise if CHA2DS2- VASc is ≥2

H/ O Intracranial haemorrhage (CHADS≥ 3 ) Unexplained major ex tra cranial bleed within last 6/ 12 PU within last 3/ 12 Alcohol abuse Advanced impaired cognit ive funct ion/ dementia Drug interact ion

Interacts with cranberry juice and foods with high amounts of Vit K e.g. cabbage, spinach, broccoli, sprouts

H/ O intracranial haemorrhage (not always a C/ I - seek specialist advice) Oesophageal varices (depends on classif icat ion) Previous hypersensit ivity/ adverse react ion (consider cardiology opinion) Advanced malignancy/ terminal illness Pregnancy Signif icant thrombocytopenia (platelet count < 50) Acute clinically signif icant bleed (incl within 72hrs of major surgery with risk

of severe bleeding) Severe renal impairment (eGFR stage 5) Decompensated liver disease (baseline INR .1.5)

Ensuring understanding why oral ant icoagulants are indicated in AF Ensuring pat ient understands that AF increases the risk of stroke

by 5 – 6 t imes compared to non- AF pat ient Ensuring pat ient understands that stroke in AF is severely disabling

or fatal Understanding how to use CHA2DsVASc table and to explain risk Use of Pat ient Decision Aids Involving family and carers in decision making, esp where there

may be co- morbidity esp dementia, falls, frailty, very elderly

Warfarin is the commonest VKA used Recent audit data suggest the majority of CCGs are advising use of

warfarin as f irst line data ( around 73% ) NICE guidance – use of VKA or any of the available NOAC Warfarin init iat ion is via local pathway NOAC init iat ion variable across CCGs, usually secondary care led,

but increasingly from primary care Warfarin init iat ion is usually done as low dose init iat ion, with

init iat ing dose varying between 1 – 3 mg; t ime to reach therapeut ic range of INR is usually between 14 days to 28 days

High dose warfarin init iat ion is no longer advised, where there is need for immediate ant icoagulat ion, LMWH or NOAC can be used

Dabigatran Apixaban Edoxaban * Rivaroxaban

ActionDirect thrombin inhibitor

Activated factor Xa (FXa) inhibitor



Dose150 mg BID

110 mg BID

5 mg BID

2.5 mg BID

60 mg QD

30 mg QD

15 mg QD

20 mg QD

15 mg QD

Phase III clinical trial RE-LY 1ARISTOTLE 2

AVERROES 3ENGAGE-AF 4 ROCKET-AF 5

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www.escardio.org/EHRA

1. Connolly et al, N Engl J Med 2009; 361:1139-51 4. Ruff et al, Am Heart J 2010; 160:635-412. Granger et al, N Engl J Med 2011; 365:981-92 5. Patel et al, N Engl J Med 2011;365:883-913. Connolly et al, N Engl J Med 2011; 364:806-17

* not yet approved by EMA

Fibrinogen Fibrin

Common Pathway

Thrombin

Xa

Prothrombin

Clot

Xa Blocker

ApixabanRivaroxaban

Dabigatran

New Oral Agents

Intracranial HemorrhageAtrial Fibrillation Trials

Study NOAC VKA Outcome

RE-LY Dabigatran0.3%

Warfarin0.7%

RR 0.4095% CI 0.27-0.60

P= <0.001

ARISTOTLE Apixaban0.3%

Warfarin0.8%

HR 0.4295% CI 0.30-0.58

P = <0.001

ROCKET-AF Rivaroxaban0.5%

Warfarin0.7%

HR 0.6795% CI 0.47-0.93

P = 0.02

Dabigatran Apixaban Edoxaban * Rivaroxaban

Bioavailability 3-7% 50% 62%66% (w/o food)

~100% with food

Prodrug yes no no no

Clearance: non-renal/renal of adsorbed dose if normal renal function

20%/80% 73%/27% 50%/50% 65%/35%

Liver metabolism: CYP3A4 noyes (elimination; minor CYP3A4)

minimal (<4% of elimination)

yes (elimination)

Absorption with food no effect no effect 6-22% more +39%

Intake with food? no nono official recommendation

yetmandatory

Absorption with H2B/PPI plasma level -12 to -30% no effect no effect no effect

Asian ethnicity plasma level +25% no effect no effect no effect

GI tolerability dyspepsia 5-10% no problem no problem no problem

Elimination half-life 12-17h 12h 9-11h 5-9h (young)/11-13h (elderly)

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* not approved yet

All NICE approved (Licensed for use in non- valvular AF with ≥1 CHA2DS2VASc)

TTR < 65% (invest igate) No rout ine monitoring No food interact ions Check renal funct ion at least annually C/ I similar to Warfarin Still risk of bleeding - monitor those at high risk Patient alert cards They are on an ant icoagulant!

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Card can be downloaded in a printer-ready form or in a ppt format that can be configured to the local language from www.NOACforAF.eu

Three levels of alert:

Red – contraindicated/not recommended for use

Orange – adapt NOAC dose

◦ dabigatran: 150 mg to 110 mg BID

◦ rivaroxaban: 20 mg to 15 mg QD

◦ apixaban: 5 mg to 2.5 mg BID

Yellow – consider dose reduction if two concomitant yellow interactions

Where no data available, NOACs not recommended yet

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Dabigatran Apixaban Edoxaban Rivaroxaban

Atorvastatin P-gp/ CYP3A4 +18% no data yet no effect no effect

Digoxin P-gp no effect no data yet no effect no effect

Verapamil P-gp/ wk CYP3A4+12–180%

no data yet+ 53% (slow release)

minor effect

Diltiazem P-gp/ wk CYP3A4 no effect +40% No data minor effect

Quinidine P-gp +50% no data yet +80% +50%

Amiodarone P-gp +12–60% no data yet no effect minor effect

Dronedarone P-gp/CYP3A4 +70–100% no data yet +85% no data yet

Ketoconazole; itraconazole; voriconazole; posaconazole;

P-gp and BCRP/ CYP3A4 +140–150% +100% no data yet up to +160%

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Red – contraindicated; orange – reduce dose; yellow – consider dose reduction if another yellow factor present; hatching – no data available; recommendation made from pharmacokinetic considerations

All NOACs are anticoagulants and hence can cause serious bleeding.

All NOACs have some drug-drug interactions (DDIs).

AF population is a fragile patient population.

Patients should return for ongoing review according to a predetermined schedule.

Follow-up can be undertaken by specialist or GP with experience in the field and/or appropriate secondary care physicians.

Nurse co-ordinated AF clinics may be used. 1

1. Berti et al, Eur Heart J, 2013 (Epub ahead of print)

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Interval Comments

Compliance Each visit

Inspect remaining medication

Stress importance of compliance

Inform about compliance aids

Thrombo-embolism Each visit Cerebral, systemic and pulmonary circulation

Bleeding Each visit“Nuisance” bleeding – prevention possible?

Bleeding with risk or impact on QoL – prevention possible? Need to revise dose?

Side effects Each visit Continuation? Temporary cessation with bridging? Change of anticoagulant drug?

Co-medications Each visitPrescription or over-the counter drugs?

Even temporary use can be risky

Blood sampling

Yearly

6-monthly

3-monthly

on indication

Haemoglobin, renal, liver function

Renal function if CrCl 30-60 ml/min or if on dabigatran and aged >75 years or fragile

If CrCl 15-30 ml/min

If intercurring condition may impact renal or hepatic function.

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Stroke awareness and measures to prevent stroke Rate control Assessment of symptoms for rhythm control Who to contact for advice if needed Psychological support if needed Up- to- date comprehensive information on:◦ Causes, effects and complicat ions of AF◦ Management of rate and rhythm control◦ Anticoagulat ion◦ Support networks

Individual approach - making each contact count

Populat ion approach - employing strategies to improve detect ion of AF and increasing ant icoagulat ion rates in this cohort

Opportunist ically Targeted

Especially in the over 65’s Those with symptoms:-

Breathlessness, palpitat ions, dizziness

Flu clinics NHS Health Check Housebound Care Homes

Hypertensives Diabet ics Exist ing CVD

dr mammen ninan gpwsi in cardiology - home - the … · af affects up to 835,000 people in england...

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