Tromboprofilaxis en FA

1
Focus on Thromboprophylaxis
Carlos Jerjes Sanchez, MDHead of Emergency
Department Hospital de Cardiologia No.
34 Monterrey, Nuevo Leon, Mexico
2
Focus on Thromboprophylaxis

• Brief overview
• Inflammation
• Hypercoagulable state
• Thrombogenesis
• Risk stratification
• Current and future therapeutic approaches

3
Unmet Answers in AF
What is the incidence?
Who is at risk for atrial fibrillation?
Is it possible to identify preinflammatory and
prethrombotic state?
Is the thromboembolic risk quantifiable?
How complex is coagulation cascade?
Modified from Boos CJ, et al. J Thromb
Thrombolysis. 200520189-190.
4
Unmet Answers in AF
What is the incidence?
5
Incidence of NV Atrial Fibrillation
Triple or quadruple number of patients 2050
Singh BN. Eur Heart J. 200810H2-H3.
6
Unmet Answers in AF
Who is at risk for atrial fibrillation?
7
NVAtrial Fibrillation and CV Diseases
Associated reduced left ventricular function,
exercise tolerance, quality of life and 2-fold
increase in cardiac mortality
Singh BN. Eur Heart J. 200810H2-H3.
8
Unmet Answers in AF
Is it possible to identify preinflammatory and
prethrombotic state?
9
Unifying the Model of Vascular Disease
Inflammation
Insulin resistance Type II diabetes Dyslipidemia H
ypertension
Cytokines
1. Modified from Dzau VJ. Hypertension.
2001371047-1052.
2. Modified from Moreno PR, et al. J Am Coll
Cardiol. 2004442293-2300.
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Mechanisms Proposed Unifying Model in AF
Inflammation Cytokines IL-6, TNF-a, IL-1B, IFN-y,
TGF-ß, IL-8 IL-6 Acute phase protein Creactive
protein
Complement Cascade
Thrombosis
? NO Coagulation Factor VIII, fibrinogen, D-Dimer,
prothrombin Factor 1.2, thrombin antithrombin
complex Platelets Pselectin B-thromboglobulin, Pl
atelet factor 4
C3 C4 Cohort of 1011 patients 4-year
follow-up Normal components High levels of CRP No
high incidence of AF Am J Cardiol. 200697245
Atrial fibrillation Myocyte calcium
overload Atrial myocyte apoptosis CRP acts as an
opsonin Binds atrial myocytes Local inflammation
and CA
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Mechanisms Proposed Unifying Model in AF
Nutrients, inactivity, smoking, obesity, stress,
MS, age, BMI, hypertension, heart failure
Inflammation
Thrombin
Obesity Systemic inflammation Neurohormonal
activation Increased arterial stiffness
Obstructive sleep apnea Teresa SM. Eur Heart J.
2008292227.
Platelet activation
Fibrin rich - clot
12
Natural History of Atrial Fibrillation
Loss of normal endocardial thromboresistance
Factors Xa - IIa Exhibiting procoagulant prolifer
ative and tissue remodeling potential
Tissue factor Expressed cellular elements
leading to incremental clot growth
Thrombus formation Embolization
13
Unmet Answers in AF
How complex is coagulation cascade?
14
Triad of Virchow 2008
Abnormal vessel wall

• Inflammation, endothelial dysfunction,
  atherosclerosis

Abnormal blood flow

• Hemorheology and turbulence at bifurcations and
• stenotic regions

Abnormal blood constituents

• Platelet function, coagulation, fibrinolysis,
  metabolic, hormonal factors

Genetics
JerjesSanchez C. Eur Heart J. 2005263-4.
15
CHADS2 Risk Criteria and Scoring
SCORING Low risk 0 Intermediate risk 1
2 High risk 3 or more
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Risk Stratification and Antithrombotic Use
Modified from Turpie AG. Eur Heart J.
200829155-165.
17
Risk Stratification, Antithrombotics, and DC-CV
in AF
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Predictors of CNS Bleeding

• Advancing age ( gt 75 years)

• Hypertension (SBP gt 160 mmHg)

• History of cerebrovascular disease

• Intensity of anticoagulation

• Leukoariosis (white matter hyperdensities /
  hyperintensities) CT / MRI

• Microbleeds by gradient T2 MRI

Hart RG, et al. J Thromb Thrombolysis.
20082526-32.
19
Risk of stroke
International Normalized Ratio
Risk of ICH
Odds ratio
The estimated odds ratio subdural hemorrhage
increased fold as INR increased above
INR lt 2.0 results in a higher risk of stroke
20
Metaanalyses RCTs Antithrombotics Therapies AF
Hart RG, et al. J Thromb Thrombolysis.
20082526-32.
21
Relationship Between INR, Death, and CNS Events
Hart RG, et al. J Thromb Thrombolysis.
20082526-32.
22
New Anticoagulants
Hirsch J, et al. Circulation. 2007116552-560.
23
New Anticoagulants
Hirsch J, et al. Circulation. 2007116552-560.
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Oral Anticoagulants
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Subcutaneous and IV Anticoagulants
Hirsch J, et al. Chest. 2008133141S-159S.
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Status of New Anticoagulants
Modified from Hass S. J Thromb Thrombolysis.
20082552-60.
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Will these new anticoagulants replace the
established drugs? How will these new ACGs fit
into the therapeutic armamentarium of the
practicing cardiology?
Hirsch J, et al. Circulation. 2007116552-560.