Nova antitrombotska terapija
Prof. dr sc. Mirza Dilić, FESC, FACC
Klinički Centar Sarajevo
šef Centra za srce
direktor Internih Klinika i Odjeljenja
Dilić M, MD, PhD, Institute of Vascular Diseases, Clinical Center Sarajevo, Bosnia and Herzegovina
Dilić M, MD, PhD, Institute of Vascular Diseases, Clinical Center Sarajevo, Bosnia and Herzegovina
Dilić M, MD, PhD, Institute of Vascular Diseases, Clinical Center Sarajevo, Bosnia and Herzegovina
Dilić M, MD, PhD, Institute of Vascular Diseases, Clinical Center Sarajevo, Bosnia and Herzegovina
Dilić M, MD, PhD, Institute of Vascular Diseases, Clinical Center Sarajevo, Bosnia and Herzegovina
Dva tipa tromboze
• Venski tromboembolizam
(dominantno preko trombina)
• Aterotromboza
(dominantno preko trombocita)
Dilić M, MD, PhD, Institute of Vascular Diseases, Clinical Center Sarajevo, Bosnia and Herzegovina
VTE - venski tromboembolizam
•
DVT (duboka venska tromboza)
• PE (plućna embolija)
• Profilaksa
• Tretman
Dilić M, MD, PhD, Institute of Vascular Diseases, Clinical Center Sarajevo, Bosnia and Herzegovina
VTE - venski tromboembolizam
• DVT (duboka venska tromboza)
• PE (plućni tromboembolizam)
• AT (atrijalni trombi)
Dilić M, MD, PhD, Institute of Vascular Diseases, Clinical Center Sarajevo, Bosnia and Herzegovina
Dilić M, MD, PhD, Institute of Vascular Diseases, Clinical Center Sarajevo, Bosnia and Herzegovina
Dilić M, MD, PhD, Institute of Vascular Diseases, Clinical Center Sarajevo, Bosnia and Herzegovina
Dilić M, MD, PhD, Institute of Vascular Diseases, Clinical Center Sarajevo, Bosnia and Herzegovina
Dilić M, MD, PhD, Institute of Vascular Diseases, Clinical Center Sarajevo, Bosnia and Herzegovina
Centralno
mjesto
trombina
i
trombocita
Dilić M, MD, PhD, Institute of Vascular Diseases, Clinical Center Sarajevo, Bosnia and Herzegovina
Thrombin ~ antitrombin III
Antitrombin III
Dilić M, MD, PhD, Institute of Vascular Diseases, Clinical Center Sarajevo, Bosnia and Herzegovina
Antiagregantni faktor
Antiagregantni
faktor
Dilić M, MD, PhD, Institute of Vascular Diseases, Clinical Center Sarajevo, Bosnia and Herzegovina
Standardna terapija
Warfarin, acenokumarol.......
Heparin
LMW Heparin
Aspirin
Dipiridamol
Tiklopidin
Klopidogrel
Dilić M, MD, PhD, Institute of Vascular Diseases, Clinical Center Sarajevo, Bosnia and Herzegovina
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
Dilić M, MD, PhD, Institute of Vascular Diseases, Clinical Center Sarajevo, Bosnia and Herzegovina
Propisivanje VKA u AF
No anticoagulation
64%
N=23,657
Medicare cohort, USA1
VKAs
67%
N=5,333
EuroHeart survey2
55%
N=11,409
ATRIA cohort3
(managed care system,
California, USA)
Dilić M, MD, PhD, Institute of Vascular Diseases, Clinical Center Sarajevo, Bosnia and Herzegovina
Novel antithrombotics
Dilić M, MD, PhD, Institute of Vascular Diseases, Clinical Center Sarajevo, Bosnia and Herzegovina
FDA approval
EMA approval
Appropriate balansing between clinical benefit
and risk of bleeding.
Dilić M, MD, PhD, Institute of Vascular Diseases, Clinical Center Sarajevo, Bosnia and Herzegovina
FDA approval
Safety
 Similar rates of bleeding and adverse
events
 Less CVI and fatal GI bleeding
Dilić M, MD, PhD, Institute of Vascular Diseases, Clinical Center Sarajevo, Bosnia and Herzegovina
Dilić M, MD, PhD, Institute of Vascular Diseases, Clinical Center Sarajevo, Bosnia and Herzegovina
Direct inhibitor Xa - Rivaroxaban
Rivaroxaban vs. warfarin
VTE, AF, ACS
Ortopedska hirurgija
Redukcija trombotskih komplikacija
Kontrolisano krvarenje
Dilić M, MD, PhD, Institute of Vascular Diseases, Clinical Center Sarajevo, Bosnia and Herzegovina
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
Dilić M, MD, PhD, Institute of Vascular Diseases, Clinical Center Sarajevo, Bosnia and Herzegovina
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
Dilić M, MD, PhD, Institute of Vascular Diseases, Clinical Center Sarajevo, Bosnia and Herzegovina
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."
Dilić M, MD, PhD, Institute of Vascular Diseases, Clinical Center Sarajevo, Bosnia and Herzegovina
Dilić M, MD, PhD, Institute of Vascular Diseases, Clinical Center Sarajevo, Bosnia and Herzegovina
Direct thrombin inhibitor Dabigatran
Dabigatran
VTE, AF, ACS
Ortopedska hirurgija
Redukcija trombotskih komplikacija
Kontrolisano krvarenje
RE-LY Trial
RE-COVER Trial
Dilić M, MD, PhD, Institute of Vascular Diseases, Clinical Center Sarajevo, Bosnia and Herzegovina
FDA approval
 Dabigatran 150 mg. twice daily
 Dabigatran 75 mg. daily
Dilić M, MD, PhD, Institute of Vascular Diseases, Clinical Center Sarajevo, Bosnia and Herzegovina
Novel antiplatelets
 Prasugrel
 Ticagrelor
 Cangrelor (I.V)
Dilić M, MD, PhD, Institute of Vascular Diseases, Clinical Center Sarajevo, Bosnia and Herzegovina
Prasugrel
ADP inhibitor
5-9 x jači effect od clopidogrela
60 mg. loading dose + 10 mg dn.
Efficacy – bleeding risk
Dilić M, MD, PhD, Institute of Vascular Diseases, Clinical Center Sarajevo, Bosnia and Herzegovina
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
Dilić M, MD, PhD, Institute of Vascular Diseases, Clinical Center Sarajevo, Bosnia and Herzegovina
ACCP Guidelines
Dilić M, MD, PhD, Institute of Vascular Diseases, Clinical Center Sarajevo, Bosnia and Herzegovina
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*
Dilić M, MD, PhD, Institute of Vascular Diseases, Clinical Center Sarajevo, Bosnia and Herzegovina
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).
Dilić M, MD, PhD, Institute of Vascular Diseases, Clinical Center Sarajevo, Bosnia and Herzegovina
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).
.
Dilić M, MD, PhD, Institute of Vascular Diseases, Clinical Center Sarajevo, Bosnia and Herzegovina
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 adjusteddose VKA therapy (target INR range, 2.0-3.0) (Grade
2B).
Dilić M, MD, PhD, Institute of Vascular Diseases, Clinical Center Sarajevo, Bosnia and Herzegovina
Dosage ???
Strictly fixed ?
Non-Responder ?
Hyper-Responder ?
Dilić M, MD, PhD, Institute of Vascular Diseases, Clinical Center Sarajevo, Bosnia and Herzegovina
Dilić M, MD, PhD, Institute of Vascular Diseases, Clinical Center Sarajevo, Bosnia and Herzegovina
ACC / AHA / ESC Guidelines
Update 2012
Dilić M, MD, PhD, Institute of Vascular Diseases, Clinical Center Sarajevo, Bosnia and Herzegovina