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7/30/2019 Pleno Pakar Blok EMS,Pc1

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Pleno Pakar Blok EMS,Pc1

Dr.Datten Bangun MSc,SpFK

Dept.Farmakologi & TherapeutikFak.Kedoktran USU

Medan


2/31

Atrial fibrillation (AF) Atrial fibrillation (AF) is the most common sustained

cardiac arrhythmia AF adversely affects cardiac haemodynamics because

of loss of atrial contraction and the rapidity andirregularity of the ventricular rate

Atrial fibrillation (AF) AF is associated with a 6-foldincrease in risk of stroke this risk can be substantiallyreduced with antithrombotic treatment

decisions regarding antithrombotic treatmentshould not be based on the temporal pattern of thearrhythmia, but on the presence or absence of riskfactors for thromboembolism in patients with AF


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Stroke prevention in patients with AF

Embolism from atrial fibrillation (AF) associated left atrial thrombi accounts forapproximately 10% of all ischemic strokes inthe United States, and

AF is associated with a 4- to 5-fold increase inthe risk of ischemic stroke, independent of cardiac valve disease


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The choice of therapy for primarystroke prevention in patients with AF

Depends on several factors, including:-estimated stroke risk,

-risk of bleeding with anticoagulation therapy-and patient preference


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Why Restore Sinus Rhythm?

Reduce symptoms Decrease stroke risk Preserve ventricular function Reduce mortality


6/31

Mechanisms of Atrial Fibrillation:Multiwavelet Reentry, Rapid Rotors

and Focal Triggers


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Risk stratification

Two widely used systems are:1. the CHADS 2 scoring system and

2. theAmerican College of Cardiology/AHA/European Society of Cardiology (ACC/AHA/ESC) 2006 guidelinerecommendations for stroke riskstratification in AF patients


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Antiarrhythmic Drugs for

Treatment of Atrial Fibrillation Class I Drugs

IA (avoid in patients with CAD, LVH, CM) Disopyramide for vagally mediated AF

IC (avoid in pts with CAD, LVH, CM) Flecainide 100-225mg bid Propafenone 150-225 mg tid or bid

Class III Drugs Sotalol 80-160 mg bid (may not be tolerated in CHF) Dofetilide 0.125-0.625 mg bid (may be used in CHF,

but must watch QTc, K+, creatinine) Amiodarone 100-200 mg daily (drug of choice in pts

with CHF)


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Who requires anticoagulation ?

Annals of Internal Medicine, 2003:139;1009-1017


10/31

CHADS2 Risk Score Congestive Heart Failure = 1 Hypertension = 1 Age > 75 years = 1 Diabetes = 1 Stroke = 2

=Anticoagulation with full dose warfarin (INR 2-3) isrecommended in any patient with CHADS2 score 2 ,= with ASA 81-325 mg or warfarin if CHADS2 score is 1,

= no anticoagulation if CHADS2 score is 0


11/31

Indications of Anticoagulant Therapy

Treatment and Prevention of Deep VenousThrombosis

Pulmonary Emboli

Prevention of stroke in patients with atrialfibrillation, artificial heart valves, cardiac thrombus. Ischaemic heart disease During procedures such as cardiac catheterisation

and apheresis.


12/31

Anticoagulant Use

Anticoagulant drugs help prevent the developmentof harmful clots in the blood vessels by lessening theblood's ability to cluster together

The function of these drugs is often misunderstoodbecause they are sometimes referred to as bloodthinners; they do not in fact thin the blood

These drugs will not dissolve clots that already haveformed, but it will stop an existing clot frombecoming worse and prevent future clots


13/31

Anticoagulant Drugs Heparin and warfarin are the two traditional

anticoagulants Anticoagulants are used for acute coronary

syndromes, deep-vein thrombosis (DVT),pulmonary embolism (PE), and heart surgery

Thrombus - A blood clot that forms abnormallywithin the blood vessels

Embolus - When a blood clot becomes dislodged

from the vessel wall and travels through thebloodstream It is also given to certain people at risk for

forming blood clots, such as those with artificial

heart valves or who have atrial fibrillation (AF)


14/31

History of Warfarin

1930s: cows hemorrhaging after eating spoiled sweetclover silage

1939: bishydroxycoumarin (dicoumarol) identified

1948: potent form as rodenticide Called Warfarin (Wisconsin Alumni Research

Foundation)Anticoagulant in humans? No, too toxic!? 1951: Army inductees failed attempt at suicide with

high dose of warfarin rodenticide Clinical use for over 60 years

Vitamin K antagonists


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Warfarin

Adjusted-dose warfarin (target INR 2-3)anticoagulation is highly effective forpreventing stroke in patients with AF, andalso reduces stroke severity and poststrokemortality


16/31

EnhancesAntithrombin Activity


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EnhancesAntithrombin Activity

Warfarin

Vi i K i


18/31

Problems with Warfarin

Food and drug interactions

Genetic variation in metabolism

narrow therapeutic window

slow onset of action

overlap with parenteral drugs

dosage adjustments &

freq. monitor with INR


Vi i K i


19/31

Effect on Coagulation Vitamin K dependent clotting factors: Factors II, VII, IX, and X

XIIXIIa

XIa XI

IXa IX

VIIIa

VIIaTF

X XaVa

II (prothrombin) IIa (thrombin)

Fibrinogen FibrinStabilized

Fibrin

XIII XIIIa

Extrinsic pathway

Intrinsic pathway

Common pathway


Vit i K t i t


20/31

Warfarin Adminstered orally, intravenously, or rectally Bioavailabily nearly complete; absorption dampered

by food Peak concentration 2 - 8 hr Binds to albumin 99% of time Can cross placental barrier Racemic mixture: S form by CYP2C9; R by CYP1A2,

minor pathway CYP2C19, and minor pathway CYP3A4 half-life: 25 - 60 hr; Excreted in urine and stool

Food-drug & drug-drug interactions: extensive!!

Toxicities: bleeding, fetal bone abnormalities



21/31

( )Patients PT in Seconds

Mean Normal PT in SecondsINR =

ISI

INR = International Normalised RatioISI = International Sensitivity Index

INR Equation

Target INR

DVT, PE, Atrial Fibrillation: 2-3

Artificial Cardiac Valve: 3-3.5


22/31

INR: International Normalised Ratio

A mathematical correction (of the PT ratio) fordifferences in the sensitivity of thromboplastinreagents

INR is the PT ratio one would have obtained if thereference thromboplastin had been used

Allows for comparison of results between labs andstandardises reporting of the prothrombin time


23/31

Some findings

The Atrial fibrillation Clopidogrel Trial withIrbesartan for prevention of Vascular Events(ACTIVE A and ACTIVE W) has shown that:1.adjusted-dose warfarin is superior toclopidogrel plus aspirin, and

2. clopidogrel plus aspirin is superior to aspirin

alone in preventing stroke in patients with AF


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Hazardous effect of warfarin

However, the risk of major bleedingcomplications, such as ICH, is higher withwarfarin therapy than with the antiplateletagents. Regular monitoring of patients onwarfarin is required, especially during the first3 months of treatment, when the risk of

bleeding is greatest.


25/31

Adjusted-dose warfarin Adjusted-dose warfarin anticoagulation is

recommended for all patients with nonvalvular AF athigh risk or moderate risk of stroke.

Aspirin is recommended for low- and moderate-risk

patients with AF. For high-risk patients in whom anticoagulation is

unsuitable, a combination of clopidogrel and aspirinmay provide more protection against stroke thanaspirin alone.

In addition to antithrombotic prophylaxis, managingblood pressure aggressively in elderly patients with AFmay be useful.


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Warfarin:Major Adverse Effect Haemorrhage

Factors that may influence bleeding risk: Intensity of anticoagulation Concomitant clinical disorders Concomitant use of other medications Quality of management


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Warfarin

Effective Reversible Inexpensive

Slow onset of action Regular monitoring Food interraction Medication interraction Difficult titration-regular dose adjustments


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Secondary Prevention of Stroke

Secondary prevention can be summarized by themnemonic A, B, C, D, E, as follows:

A - Antiaggregants (aspirin, clopidogrel, extended-release dipyridamole, ticlopidine) andanticoagulants (warfarin)

B - Blood pressure lowering medicationsC - Cessation of cigarette smoking, cholesterol-

lowering medications, carotid revascularizationD - DietE - Exercise


29/31

Sekian,

Terima kasih


30/31

Classification Systems

There are 2 systems which use aetiology astheir basis:

-Stroke Data Bank (Gross, 1986)

-TOAST (Adams, 1993)

The main difficulty with this system isperforming the necessary technicalexaminations on all patients


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TOAST Classification

There are 5 diagnostic sub-types of ischaemicstroke:

1.Large artery atherosclerosis

2.Cardioembolism

3.Small vessel occlusion (lacunar)

4.Other determined aetiology5.Undetermined aetiology

Multiple possible aetiologies (No.6)

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