PREVENTION OF STROKE IN ATRIAL FIBRILLATION

WHEN , WHAT AND HOW TO DO IT…

AF Workshop 2014

THE FACTS….ABOUT ATRIAL FIBRILLATION (AF)

Commonest arrhythmias in clinical practice

AF affects 1–2% of the population

The prevalence of AF increases with age

The lifetime risk of developing AF is 25% in those who have

reached the age of 40

THE BAD…..OF AF

Death - death rates are doubled by AF vs

in sinus rhythm.

- mostly due to thromboembolic

stroke

Stroke - 5x risk stroke in non valvular AF

- 17x risk stroke in valvular or

rheumatic heart disease

- No 1 cause in embolic stroke

TYPES OF AF

Valvular atrial fibrillation :

-prosthetic valve

-haemodynamically

significant valvular disease

Non valvular atrial

fibrillation

Paroxysmal

Persistent

Permanent

PAROXYSMAL AF

AF occurs and terminates by itself

Usually resolves spontaneously within 48 hrs

up to 7 days

PERSISTENT AF

AF episode either :

-lasts longer than 7 days

or

-requires termination by cardioversion - DRUGS

- DC SHOCK

PERMANENT AF

AF that decided to be permanent because

- cannot be terminated in what means of treatment,

- low success or unlikely to achieve sinus rhythm,

- failed cardioversion

- decided not to try cardioversion

- when the presence of the arrhythmia is accepted by

the patient (and physician).

Usually long standing

Most have significant structural heart disease.

PRINCIPLES OF AF MANAGEMENT

(1) Rate control.

(2) Prevention of thromboembolism.

(3) Optimal management of etiology

concomitant disease & complications.

(4) Symptom relief.

(5) Correction of rhythm disturbance.

PREVENTION OF THROMBOEMBOLISM

The only treatment that reduce mortality in AF

is prevention of thromboembolic stroke

Antithrombotic drugs ( oral anticoagulant (OAC)

& antiplatelet) are the only drugs that reduce

mortality and stroke in AF

Trials - oral anticoagulant - is the best drug

(reduce stroke by 50-80% ) compare to

antiplatelet

PREVENTION OF THROMBOEMBOLISM

Main problems nowadays

- not anticoagulated or given antiplatelet

- subtherapeutic INR when on warfarin

- irregular INR monitoring

- unsure which patient will benefit from

anticoagulation

- unaware of newer anticoagulant

DO ALL PATIENTS WITH AF NEED ANTICOAGULANT?

VALVULAR AF NON VALVULAR AF

NEED ANTICOAGULANT

WARFARIN

Depends on - risk factors of stroke

2 main scoring regime for selection of patient

for anticoagulant or antiplatelet or none

- CHADS2 SCORE

- CHA2DS2-VASC SCORE

-NONE

-ANTIPLATELET

-ORAL ANTICOAGULANT

CHADS2 SCORE ANTITHROMBOTIC THERAPY

0 → ASPIRIN or none

1 → ORAL ANTICOAGULANT or aspirin

≥ 2 → ORAL ANTICOAGULANT

* Heart failure or LVEF ≤ 40%

*

CHA2DS2-VASc SCORE

CHA2DS2-VASc score antithrombotic therapy

0 → none or aspirin

1 → oral anticoagulant or aspirin

≥ 2 → oral anticoagulant

Vascular disease : MI, PVD, Aortic plaque * LVEF ≤ 40%

*

WHICH SCORING SYSTEM ?????

CHADSVASc – provides a more accurate estimation of risk

AF

(even paroxysmal)

VALVULAR VS NON VALVULAR

( at least echocardiography )

VALVULAR NON VALVULAR

ONLY :

- ORAL ANTICOAGULANT

CHADS2 OR CHA2DS2-VASc SCORE

ANY ONE OF THESE :

- NONE

- ANTIPLATELET

- ORAL ANTICOAGULANT

NON VALVULAR AF

STRATIFY BLEEDING RISK

≥ 3points : HIGH RISK

DIRECT THROMBIN INHIBITOR direct factor Xa inhibitor

DABIGATRAN RIVORAXABAN

APIXABAN

NOVEL ANTICOAGULANTS -NOACs

WARFARIN VS NOACs

RE- LY : DABIGATRAN VS WARFARIN

NET CLINICAL BENEFIT AND COMPONENTS

CharacteristicDabigatran110 mg BID

Dabigatran150 mg BID

WarfarinP value

D 110 mg vs. W

P valueD 150 mg

vs. W

Patients (n) 6015 6076 6022 – –

Net clinical benefit 7.34 7.11 7.91 0.09 0.02

SSE 1.54 1.11 1.71<0.001 (NI)

0.30 (Sup)

<0.001 (NI)

<0.001 (Sup)

Death 3.75 3.64 4.13 0.13 0.051

Major bleeding 2.87 3.32 3.57 0.003 0.32

Pulmonary embolism 0.12 0.15 0.10 0.71 0.30

Myocardial infarction 0.82 0.81 0.64 0.09 0.12

Data represent %/yr; *Net clinical benefit was predefined as the composite of stroke/systemic embolism (SSE),

myocardial infarction, death or major bleeding; BID = twice daily; D = dabigatran; NI = non-inferior; Sup = superior; W =

warfarin

Connolly SJ et al. N Engl J Med 2010;363:1875–6Disclaimer: Dabigatran etexilate is now approved for clinical use in stroke prevention in atrial fibrillation in certain countries.

Please check local prescribing information for further details Dec 2011

CONCLUSIONS

Dabigatran has been shown to concurrently reduce both thrombotic and

haemorrhagic events

Both doses of dabigatran provide different and complementary advantages

over warfarin

150 mg BID has superior efficacy with similar bleeding

110 mg BID has significantly less bleedings with similar efficacy

Similar net clinical benefit was seen between the two dabigatran doses

The advantages of dabigatran compared with warfarin regarding the main

efficacy and safety outcomes were irrespective of the quality of INR control

with warfarin, and were consistent with the overall RE-LY study results

BID = twice daily; INR = international normalized ratio

Connolly SJ et al. N Engl J Med 2009;361:1139–51;

Connolly SJ et al. N Engl J Med 2010;363:1875–6;

Wallentin L et al. Lancet 2010;376:975–83Disclaimer: Dabigatran etexilate is now approved for clinical use in stroke prevention in atrial fibrillation in certain countries.

Please check local prescribing information for further details Dec 2011

ROCKET-AF: RIVAROXABAN VS WARFARIN

Event rates per 100 patient-years; ITT = intention to treat

Patel MR et al. N Engl J Med 2011;365:883–91Disclaimer: Rivaroxaban is only approved for clinical use in stroke prevention in atrial fibrillation in the USA.

Please check local prescribing information for further details

HR 0.88 (95% CI: 0.75–1.03)

P<0.001 (non-inferiority)

2.1 2.4Event rate

Rivaroxaban Warfarin

Primary efficacy outcome

100

0

Days since randomization

Cu

mu

lati

ve e

ven

t ra

te (

%)

Warfarin

60

40

20

0120 240 360 480 600 720 840

80

Rivaroxaban

7081 6879 6683 6470 5264 4105 2951 1785

7090 6871 6656 6440 5225 4087 2944 1783

Rivaroxaban

Warfarin

No. at risk

90

50

30

10

70

6

0

2

0120 240 360 480 600 720 840

4

5

1

3

Dec 2011

ARISTOTLE: APIXABAN VS WARFARIN

CI = confidence interval; HR = hazard ratio; RRR = relative risk reduction

Granger CB et al. N Engl J Med 2011;365:981–92Disclaimer: Apixaban is not approved for clinical use in stroke prevention in atrial fibrillation.

This information is provided for medical education purposes only

Apixaban 212 patients, 1.27% per year

Warfarin 265 patients, 1.60% per year

HR 0.79 (95% CI 0.66–0.95)

P (superiority)=0.011

No. at risk

Apixaban 9120 8726 8440 6051 3464 1754

Warfarin 9081 8620 8301 5972 3405 1768

P (non-inferiority)<0.001

21% RRR

4

3

2

1

0

Pe

rce

nt

wit

h e

ven

t

0 6 12 18 24 30

Months

Warfarin

Apixaban

Oct 2011

HOW TO START DABIGATRAN

?

MONITOR

- 3-6monthly with RFT

- 3 monthly in elderly ,renal

impairment & high risk of

bleeding

- No need regular APTT or INR

HOW TO START RIVAROXABAN

CHADS2 OR CHA2DS2-VASc SCORE ≥ 1

Creatinine Clearance-CrCl

< 30 ml/min 30 - 49 ml/min ≥ 50 ml/min

Rivaroxaban 15mg OD Rivaroxaban 20mg ODAVOID*

WARFARIN

Ensure : -no active bleeding/coagulopathy/thrombocytopaenia

-no significant liver disease

-avoid certain drugs

*Some recommend in non valvular AF : avoid only if CrCl < 15ml/min & use 15mg OD

if CrCl 15-49ml/min

For VTE prophylaxis & Rx : avoid only if CrCl < 30 ml/min

MONITOR

- 3-6monthly with RFT

- 3 monthly in elderly ,renal

impairment & high risk of bleeding

- No need regular APTT or INR

HOW TO START, MONITOR WARFARIN

A. Educate patient :

1. Indication and action of Warfarin

2. INR (International Normalized Ratio) monitoring, dose adjustments and duration of therapy

3. Possible side effects of Warfarin, including signs and symptoms of bleeding

4. Drug interactions

5. Dietary implications on Warfarin

6. Special considerations on Warfarin: illness, interruption in therapy, or as indicated

7. Importance of compliance with lab work, telephone calls, and appointments

HOW TO START, MONITOR WARFARIN

B. Firstly do …A.Bleeding risk must be assessed

prior to initiation of Warfarin therapy.

B.Baseline Hgb is assessed and

followed annually. A low Hgb will be

repeated in 6 months.

C.Initiation of Warfarin at a dose of 4-

5 mg daily is recommended, with

smaller doses indicated for the

elderly or debilitated patient.

D.Loading doses are not

recommended.

≥ 3points: HIGH RISK

≥ 3points: HIGH RISK

HOW TO START, MONITOR WARFARIN

1. Baseline INR is recommended

prior to initiating warfarin

therapy to assess sensitivity.

2. An INR within the last 48 hrs is

acceptable as a current baseline

INR

3. Check initial INRs 3-4 days after

start of therapy.

a. For a new patient, INR checks be

done weekly for 2-3 weeks ,then

b. INR check every 2 weeks are

usually required for the next 2-3

weeks, then monthly

c. INR check at 4-8 weeks intervals

if stable. The most is 12 weeks.

• Target INR (mostly) : 2.0-3.0

• Mechanical valve : depends on

type usually either –

2.0-3.0 or 2.5-3.5

ADJUSTING THE WARFARIN DOSE & TROUBLE SHOOTING…

NEED TO SWITCH TO DABIGATRAN/RIVAROXABAN

IF ON WARFARIN:

• if INR <2.0 – start immediately

Dabigatran/Rivaroxaban

• If INR 2.0-3.0 – stop for 2d then

start Dabigatran/Rivaroxaban

• If INR > 3.0 – stop for 2d, repeat

INR ,once INR < 2.0 start

Dabigatran/Rivaroxaban

IF ON LMWH /Fondaparinux

• Start

Dabigatran/Rivaroxaban 0-

2hrs of next schedule dose

IF ON IV HEPARIN

• Start

Dabigatran/Rivaroxaban

when infusion stops

IF PATIENT CANNOT TAKE ANTICOAGULANT

NON VALVULAR AF WITH CHADS2 OR CHA2DS2-VASc SCORE ≥ 1

VALVULAR AF ( EXCLUDE MECHANICAL PROSTHETIC VALVE )

ANTICOAGULANT IS STILL THE BEST

IF UNABLE TO TAKE OR REFUSE ANTICOAGULANT

The next best is Aspirin + Clopidogrel

If Clopidorel not available AspirinFOR MECHANICAL

PROSTHETIC VALVE

MANDATORY

WARFARIN