management of stroke anticoagulation

MANAGEMENT OF STROKE ANTICOAGULATION

Latifa Oukerraj, Jamila Zarzur

Cardiologie B, CHU Ibn Sina Rabat

Printemps de cardiologie Marrakech

8éme Edition

DISCLOSURE STATEMENT OF FINANCIAL INTEREST

I, Oukerraj. Latifa, DO NOT have a financial interest/arrangement or affiliation with one or more organizations that could be perceived as a real or apparent conflict of interest in the context of the subject of this presentation.

CASE 1 MR B.AHMED

A 67 years old right handed presented with Acute onset of left sided weakness and

inabilityto speak No history of: - chest pain, palpitation, dyspnoea - loss of conciousness, vomiting - Diabetes, smoke, stroke, TIA Past history Hypertension since 10 years, not on

regular treatement

ON EXAMINATION

BP – 170/100

Pulse 120/ min, Irregullar, all peripheral pulsation including carotide well felt

GCS-11/15

No cardiac murmur

INVESTIGATIONS

Hb, Platelets, GBP within normal limits Kidney and liver function tests- Normal ECG :

HR = 120 c/min

Atrial fibrillation (AF)

Initial CT brain:

an ischemic stroke affecting the cortex and subcortex of the right frontal and parietal lobes ( small size)

INVESTIGATIONS

Transthoracic 2D Echocardiography:

- spontaneous echo contrast in the left atrium and a clot in the left atrial appendage

- hypertrophy and diastolic dysfunction of the left ventricle. No valvular abnormality was detected.

Imaging studies of the carotid arteries and aortic arch were unremarkable

In addition to high blood pressure and AF, which of the following characteristics increases this patient’s risk of a recurrent ischemic stroke?

A - Age under 75

B - Small size of infarct

C - Presence of sludge and clot in the left atrial appendage

D - Initial stroke

EPEDIMIOLOGY

Cardioembolism accounts for 20% of ischemic strokes

The more common high risk cardioembolic conditions:

MS, mechanical prosthetic valve, recent MI, AF, and dilated myocardiopathy,

The infarct is typically larger ,the outcome is poorer: in-hospital mortality rate of cardioembolic infarction was 27.3%

Cardioembolic stroke carries increased risk of hemorrhagic transformation up to 71% of cardioembolic strokes

Early recurrent embolisms: 1-10% ===> 22% ( x 2 Mortality )

Cerebral Embolism Task Force Arch Neurol. 1986;43:71–84

Mac Dougall NJ et al. Expert Rev Neurother 2009;7:1103-15

CHADS2 -> CHA2DS2VASC

CHADS2 Risk Score

CHF 1

Hypertension 1

Age > 75 1

Diabetes 1

Stroke or TIA 2

CHA2DS2-VASc Risk

Score

CHF or LVEF < 40%

1

Hypertension 1

Age > 75 2

Diabetes 1

Stroke/TIA/ Thromboembolism

2

Vascular Disease

1

Age 65 - 74 1

Female 1From ESC AF Guidelines

http://www.escardio.org/guidelines-surveys/esc-guidelines/GuidelinesDocuments/guidelines-afib-FT.pdf

B. Ahmed B.

Ahmed B. Ahmed

ESTIMATING RISK OF STROKE

B. Ahmed

HAS-BLED BLEEDING RISK SCORE

MR B.AHMED’S RISK FOR HEMORRHAGIC STROKE

B.AhmedB.Ahmed

Given the patient’s risks of recurrent clot formation and intracranial bleeding, would you begin an anticoagulant therapy?

A- Yes

B- No

ANTICOAGULATION REDUCING STROKE RISK

Mr B. Ahmed’s risk for stroke is about 6% /year

Anticoagulation could reduce this risk by at least 2/3 compared with no anticoagulation : < 2% / year

Reducing his absolute risk of stroke by at least 4% each year

ANTICOAGULATION AND BLEEDING RISK

Mr B. Ahmed’s risk of major bleeding of 3 is about 3% to 4% per year reduced to 2%/year ( by reducing his blood pressure)

Anticoagulation may x 2 this risk

Absolute risk increase of 2% / year

Chest. 2010;138:1093-1100

3/4 of all cardioembolic strokes are fatal or disabling

the benefit of anticoagulation in Mr B. Ahmed in preventing 4 strokes per year, of which 3 are fatal or disabling, per 100 patients treated, exceed the risks of anticoagulation in causing 2 major bleeds per year per 100 patients treated, many of which are not fatal or disabling.

Given the patient’s risks of recurrent clot formation and intracranial bleeding, when would you begin anticoagulant therapy?

A - ImmediatelyB - In 1 weekC - In 2 weeksD - In 1 month

M . Paciaroni Stroke 2007

Results

RECURRENT ISCHEMIC STROKE CEREBRAL SYMPTOMATIC BLEEDING

3% VS 4.9% OR 0.68

(0.44-1.06) P=0.09

2.5% VS 0.7% OR 2.89 (1.19-

7.01)

P=0.02

M . Paciaroni Stroke 2007

RECOMMANDATIONS

Anticoagulation in Acute Stroke

Guidelines for the Early Management of Patients With Acute Ischemic Stroke Stroke 2013;44

Since Mr B.Ahmed has a moderate risk of hemorrhagic

transformation of the fresh brain infarct in the first 2

weeks -- particularly, in the first 5 days or so -- it is probably advisable to practice according to the

guidelines in this case

WHAT IF?

RECOMMANDATIONS!!!

Anticoagultion in Acute Stroke

ESO AHA/ASA

TIA OR Minor Stroke

Immediately < 2 weeks

Large Brain Infarct Size OR no controled Hypertension

> 4 weeks « Further delays »

Blood tests indicate that the patient has normal kidney and liver function. Given that anticoagulant therapy is to begin in 2 weeks, what anticoagulant regimen would you select?

A- Begin heparin in 2 weeks, then transition to warfarin

B- Begin heparin in 2 weeks, then transition to a novel anticoagulant

C- Begin warfarin after 2 weeks D- Begin a novel agent after 2 weeks

WARFARIN THERAPY

Inconvénients Avantages

Fenêtre thérapeutique étroite

Nécessité de surveillance par INR

Pas d’influence de la fonction rénale

Variation individuelle Antidote

Interactions : aliments Cout

Interactions : médicaments

Nécessité « bridging »

Guidelines for prevention of stroke in patients with ischemic stroke or transient ischemic attack: Circulation 2008; 113, 409–449

NOVEL ORAL ANTICOAGULANTS

NOACS IN STROKE PREVENTION

NON VALVULAR Afib associated to 1 or more

• History of stroke or TAI or systemic embolism

• FEVG≤40%

• NYHA ≥ 2/4

• Age ≥ 75 years

• Age ≥ 65 years associated to : diabetis, coronary

diseases or Hypertension

Labile INRs with Warfarin

NOACS IN STROKE PREVENTION

Xarelto* (Rivaroxaban) 15 et 20 mg daily (CrCl 15-50 mL/min)

Pradaxa* (Dabigatran) 75 et 150 mg twice daily (CrCl 15-30 mL/min)

Eliquis* (Apixaban) 2.5 et 5 mg twice daily (age ≥ 80 years, weight ≤ 60 kg, or

serum creatinine ≥ 1.5 mg/dL)

Blood tests indicate that the patient has normal kidney and liver function. Given that anticoagulant therapy is to begin in 2 weeks, what anticoagulant regimen would you select?

A- Begin heparin in 2 weeks, then transition to warfarin

B- Begin heparin in 2 weeks, then transition to a novel anticoagulant

C- Begin warfarin after 2 weeks D- Begin a novel agent after 2 weeks

TAKE HOME MESSAGE

2 immediate concerns after an ischemic stroke caused by cardiogenic cerebral embolism: Risk of ischemic stroke recurrence and Risk for hemorrhagic stroke due to hemorrhagic transformation of the fresh brain infarct or subsequent spontaneous

The clinical predictors are used in the CHADS2 and CHA2DS2-VASc stroke prediction indices;

Predictors of intracranial bleeding: large infarct size, increasing age, hypertension, stroke attributable to cardiogenic embolism, low platelet count; and high blood glucose;

Although the timing of initiation of anticoagulation therapy after acute stroke is controversial, it is current practice in most patients to delay therapy until 2 weeks after a stroke because the risk of intracranial bleeding is greatest during the first 2 weeks; and

Anticoagulant therapy may be initiated with heparin and then transitioned to warfarin or one of the novel agents or started directly with an oral agent

Thank you