Prof. dr sc. Mirza Dilic, FESC, FACC

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Nova antitrombotska terapija
Prof. dr sc. Mirza Dilic,
FESC, FACC
Klinicki Centar Sarajevo
šef Centra za srce
direktor Internih Klinika i
Odjeljenja
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Dva tipa tromboze

• Venski tromboembolizam
• (dominantno preko trombina)
• Aterotromboza
• (dominantno preko trombocita)

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VTE - venski tromboembolizam

• DVT (duboka venska tromboza)
• PE (plucna embolija)
• Profilaksa
• Tretman

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VTE - venski tromboembolizam

• DVT (duboka venska tromboza)
• PE (plucni tromboembolizam)
• AT (atrijalni trombi)

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Centralno mjesto trombina i trombocita
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Thrombin antitrombin III
Antitrombin III
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Antiagregantni faktor
Antiagregantni faktor
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Standardna terapija

• Warfarin, acenokumarol.......
• Heparin
• LMW Heparin
• Aspirin
• Dipiridamol
• Tiklopidin
• Klopidogrel

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Anti vitamin K - AVK per oralni antikoagulansi

• PO
• Inhibira protrombinski kompleks
• Warfarin, marivarin, acenokumarol
• Potreban monitoring PT i INR
• INR izmedju 2,0 i 3,0
• Komplikacija krvarenje
• Antidot

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Propisivanje VKA u AF
No anticoagulation
VKAs
64
67
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N11,409 ATRIA cohort3(managed care
system,California, USA)
N5,333 EuroHeart survey2
N23,657 Medicare cohort, USA1
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Novel antithrombotics
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FDA approval EMA approval
Appropriate balansing between clinical benefit
and risk of bleeding.
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FDA approval

• Safety
• Similar rates of bleeding and adverse events
• Less CVI and fatal GI bleeding

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Direct inhibitor Xa - Rivaroxaban

• Rivaroxaban vs. warfarin
• VTE, AF, ACS
• Ortopedska hirurgija
• Redukcija trombotskih komplikacija
• Kontrolisano krvarenje

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Direct inhibitor Xa - Rivaroxaban

• Rivaroxaban vs. warfarin
• VTE, AF, ACS
• Ortopedska hirurgija
• Redukcija trombotskih komplikacija
• Kontrolisano krvarenje
• RECORD Trial (VTE HR, KR) 1x10
• MAGELLAN Trial (VT) 1x10
• ROCKET Trial (AF)1x15, 1x20
• EINSTEIN Trial (VTE) 2x15
• ATLAS ACS TIMI 2 (ACS) 2 x 2,5, 2 x 5

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Direct inhibitor Xa - Apixaban

• Apixaban vs warfarin
• ACS, VTE, AF,
• Ortopedska hirurgija
• Redukcija VTE komplikacija
• Kontrolisano krvarenje
• ADVANCE Trial (HR) 2x2,5
• AVVEROES (AF) 2x5
• ARISTOTLE (AF) 2x5
• APPRAISE 2 (ACS) 2x5

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Apixaban
European Medicines Agency advisory committee has
"recommended approval" of anti-clotting drug
apixaban for use in patients with "atrial
fibrillation if it's not caused by a heart valve
problem." If the EMA take the panel's advice
and apixaban is approved, it would be eligible
for "sales in all 27 European Union member
states, as well as Iceland and Norway."
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Direct thrombin inhibitor Dabigatran

• Dabigatran
• VTE, AF, ACS
• Ortopedska hirurgija
• Redukcija trombotskih komplikacija
• Kontrolisano krvarenje
• RE-LY Trial
• RE-COVER Trial

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FDA approval

• Dabigatran 150 mg. twice daily
• Dabigatran 75 mg. daily

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Novel antiplatelets

• Prasugrel
• Ticagrelor
• Cangrelor (I.V)

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Prasugrel

• ADP inhibitor
• 5-9 x jaci effect od clopidogrela
• 60 mg. loading dose 10 mg dn.
• Efficacy bleeding risk

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Ticagrelor

• ADP direktni inhibitor - subtip P2Y12
• Reverzibilan inhibitor
• Ne aktivira se preko jetre
• 180 mg loading dose 2 x 90 mg doza maintance
• Efficacy bleeding risk

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ACCP Guidelines
2012
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CHEST 2012 9 ed. Executive Summary

• Antithrombotic Therapy and Prevention of
  Thrombosis, 9th ed American College of Chest
  Physicians Evidence-Based Clinical Practice
  Guidelines
• Guyatt GH, MD, FCCP,  Aki EA, MD, PhD, MPH,
  Crowther M, MD, Gutterman DD, MD, FCCP, Schuemann
  HJ, MD, PhD, FCCP, and for the American College
  of Chest Physicians Antithrombotic Therapy and
  Prevention of Thrombosis Panel

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Antithrombotic Therapy for Atrial Fibrillation
Nonrheumatic Atrial Fibrillation
(AF)

• For patients with AF, including those with
  paroxysmal AF, who are at low risk of stroke (eg,
  CHADS2 congestive heart failure, hypertension,
  age 75 years, diabetes mellitus, prior stroke
  or transient ischemic attack score 0), we
  suggest no therapy rather than antithrombotic
  therapy (Grade 2B).
• For patients who do choose antithrombotic
  therapy, we suggest aspirin (75 mg to 325 mg once
  daily) rather than oral anticoagulation (Grade
  2B) or combination therapy with aspirin and
  clopidogrel (Grade 2B).

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AF and intermediate risk of stroke

• For patients with AF, including those with
  paroxysmal AF, who are at intermediate risk of
  stroke (eg, CHADS2 score 1), we recommend oral
  anticoagulation rather than no therapy (Grade
  1B). We suggest oral anticoagulation rather than
  aspirin (75 mg to 325 mg once daily) (Grade 2B)
  or combination therapy with aspirin and
  clopidogrel (Grade 2B).
• For patients who are unsuitable for or
  choose not to take an oral anticoagulant (for
  reasons other than concerns about major
  bleeding), we suggest combination therapy with
  aspirin and clopidogrel rather than aspirin (75
  mg to 325 mg once daily) (Grade 2B).
• .

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AF and high risk of stroke

• For patients with AF, including those with
  paroxysmal AF, who are at high risk of stroke
  (eg, CHADS2 score 2), we recommend oral
  anticoagulation rather than no therapy (Grade
  1A), aspirin (75 mg to 325 mg once daily) (Grade
  1B), or combination therapy with aspirin and
  clopidogrel (Grade 1B).
• For patients with AF, including those with
  paroxysmal AF, for recommendations in favor of
  oral anticoagulation we suggest dabigatran 150 mg
  twice daily rather than adjusted-dose VKA therapy
  (target INR range, 2.0-3.0) (Grade 2B).

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Dosage ???

• Strictly fixed ?
• Non-Responder ?
• Hyper-Responder ?

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ACC / AHA / ESC Guidelines Update 2012
2012