Anticoagulation in

Non-Valvular

Atrial Fibrillation Dane Copeland, MD

PIH Neurology

Stroke Program Medical Director - PIH Downey

What is Atrial Fibrillation? - Rapid and irregular beating of the atria of the heart

- May be associated with palpitations, light headedness, or SOB but often no

symptoms at all

- Risk factors include HTN, valvular heart Dz, CHF, CAD, COPD, OSA,

obesity, DM II, thyrotoxicosis, smoking, and ETOH

- Affects 2-3% of the general population and is more prevalent with

advancing age

0.14% <50yo, 4% 60-70yo, 14% >80yo

Classification system

AF category Defining characteristics

First detected only one diagnosed episode

Paroxysmal recurrent episodes that stop on

their own in less than 7 days

Persistent recurrent episodes that last more

than 7 days

Permanent an ongoing long-term episode

Chronic AF & Risk of Stroke

in the 24-Year Follow-Up of

Framingham Study

Group Risk Ratio

_____________________________________________________

1. No AF or RHD 0.90

2. Chronic AF 5.60

3. RHD with chronic AF 17.56

Source: Wolf, PA et al. Neurologic Clinics 1983; 1: 317-383

Why Patients with AF

Have an Increased Risk of Stroke

Mechanism: Explanation:

Abnormal changes in blood flow Stasis in left atrium

Abnormal changes in atrial wall Dilatation, denudation, edema, and

Fibroelastic infiltration

Abnormal blood constituents. Hemostatic and platelet activation

Inflammation IL-6, hs-CRP, RAAS mediated

Growth factor changes Vascular endothelial growth factor & tissue

factor expression

Why Healthcare Providers Are

Worried About Strokes in AF:

• Approximately twice as likely to be fatal than non-AF strokes

• Functional deficits more likely to be severe

• Recurrent stroke is more frequent

Cryptogenic Stroke

Definition: Stroke of unknown origin

Large observational studies have shown that at least

50% of cryptogenic strokes are caused by AF

The rate of detection of AF in patients with cryptogenic stroke increases

with length of monitoring

EMBRACE : 30-day incidence of AF lasting at least 30 sec. found 16.1 %

CRYSTAL-AF : (s/c implantable device x 3yrs)

found 8.6% at 6mo, 12.4% at 12mo, 30% at 36mo

CHADS2 Risk Stratification in

Non-Valvular Atrial Fibrillation

CHF 1

HTN 1

Age>75 1

Diabetes 1

Stroke or TIA 2

CHADS2 Risk Stratification in

Non-Valvular Atrial Fibrillation

CHADS2 Score Risk Level Stroke Rate Recommendation

_____________________________________________________________

0 Low 1.0%/year ASA (77-325mg/d)

1 Low-moderate 1.5%/year Warfarin or ASA

2 Moderate 2.5%/year Warfarin

3 High 5.0%/year Warfarin

4 or + Very High >7%/year Warfarin

CHA2DS2-VASc Risk Stratification in

Non-Valvular Atrial Fibrillation

Range 0-9

Low = 0

Intermediate = 1

High = 2+

CHF 1

HTN 1

Age 75+ 2

Age 65 -74 1

Diabetes 1

Prior Embolism 2

Vascular Disease 1

Female 1

AHA/ASA Guidelines for First Stroke Prevention Atrial Fibrillation (AF)

• Active screening in patients >65yo in primary care settings

by pulse followed by ECG can be useful (Class IIa;

Level of Evidence [LOE] B)

• Adjusted-dose warfarin (target INR 2-3) recommended for

all patients with non-valvular AF deemed high risk & many

at moderate risk for stroke (Class I; LOE A)

• Antiplatelet therapy with ASA recommended for low risk

and some moderate risk patients with AF according to

patient preference, estimated bleeding risk, and access to

anticoagulation monitoring (Class I; LOE A)

AHA/ASA Guidelines for First Stroke Prevention Atrial Fibrillation (AF)

• For high risk patients with AF deemed unsuitable for

anticoagulation, dual antiplatelet therapy with clopidogrel

and ASA offers more protection against stroke than ASA

alone but there is an increased risk of bleeding

(Class I; LOE A)

• Aggressive management of blood pressure coupled with

antithrombotic prophylaxis in elderly patients with AF may

be useful (Class IIa; LOE B)

AHA/ASA Guidelines for Recurrent Stroke Prevention Atrial Fibrillation

• The CHADS2 or CHA2DS2-VASc Risk Stratification Scales (or other

validated scales) are recommended for use in AF patients to judge risk of

stroke or systemic embolism in clinical practice

• If unable to take oral anticoagulation give ASA alone (Class I; LOE A); risk

of bleeding with ASA + clopidogrel is similar to that of warfarin & not

indicated with a hemorrhagic contraindication anticoagulation (Class III,

LOE B)

• For patients with AF at high risk (CHADS2= 5 or 6, mechanical or

rheumatic valve) & who require temporary interruption of oral

anticoagulation, bridging with LMWH s/c is reasonable (Class IIa; LOE C)

The HAS-BLED Score Risk Score to Predict Bleeding in Anticoagulated Patients with

Atrial Fibrillation

High risk (>4%/year) 4+ Moderate risk (2-4%/year) 2-3 Low risk (<2%/year) 0-1

HTN (>160 mmHg SBP) 1

Abnormal renal or hepatic function 1-2

Stroke 1

Bleeding history or anemia 1

Labile INR (time at goal range<60%) 1

Elderly (>75yrs) 1

Drugs (antiplatelet, NSAID) or alcohol 1-2

Rhythm versus Rate Control

AFFIRM Trial

- Showed that achieving NSR does not significantly reduce risk of

stroke.

- Majority of strokes occurred in patients who stopped AC suggesting

treatment of the atrial dysrhythmia does not eliminate the thrombogenic

substrate in AF.

- The rhythm control group was more likely to experience episodes of

undetected AF reinforcing the need for AC after achieving NSR.

Wyse et al. NEJM 20002; 347 (23): 185-233.

PROTECT trial (WATCHMAN device)

- AF patients with high stroke risk & contraindications to long term

anticoagulation (warfarin vs LAA closure)

- Primary endpoint: composite of stroke, embolism, and death (CV or UE)

- initial analysis showed non-inferiority

WM device vs warfarin (3/100 pt. yr. vs 4.9/100 pt. yr. efficacy)

(Holmes et al. Lancet 2009; 374 (9689): 534-42

- 4 yr. follow-up showed WM device had significant reduction in primary

endings c/w warfarin (8.4% vs 13.9%)

(Reddy et al. JAMA 2014; 312(19): 1988-98)

PREVAIL Trial

Inclusion Criteria

NVAF patients

CHADS2 Score >=2 (or 1 with additional RF)

Exclusion Criteria

Requirement for AC other than AF

Contraindication to warfarin or ASA

Previous stroke or TIA within 90 days

PREVAIL Trial

(Safety Data)

- 7 day procedure-related complications = 4.2%

(cardiac perforation, pericardial effusion with tamponade,

ischemic stroke, device embolization and other vascular

complications )

- pericardial effusions requiring surgery = 0.4%

- pericardial effusions requiring pericardiocentesis = 1.5%

- device embolization = 0.7%

Holmes et al. JACC 64(1) 2014: 1-12.

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