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 12% 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
Characteristic
Dabigatran
110 mg BID
Dabigatran
150 mg BID
Warfarin
P value
D 110 mg
vs. W
P value
D 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;363:18756
Disclaimer: 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;361:113951;
Connolly SJ et al. N Engl J Med 2010;363:18756;
Wallentin L et al. Lancet 2010;376:97583
Disclaimer: 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;365:88391
Disclaimer: 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: 0.751.03)
P<0.001 (non-inferiority)
2.1 2.4 Event rate
Rivaroxaban Warfarin
Primary efficacy outcome
100
0
Days since randomization
C
u
m
u
l
a
t
i
v
e

e
v
e
n
t

r
a
t
e

(
%
)
Warfarin
60
40
20
0
120 240 360 480 600 720 840
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
0
120 240 360 480 600 720 840
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;365:98192
Disclaimer: 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 0.660.95)
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
P
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t

w
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e
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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 OD AVOID*
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 Aspirin

FOR MECHANICAL
PROSTHETIC VALVE

MANDATORY
WARFARIN