institute of vascular diseases clinical center university of sarajevo
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ESC-ACCP-ACC Guidelines in atherothrombosis. Institute of Vascular Diseases Clinical Center University of Sarajevo. Ključni faktori razvoja aterotromboze. - PowerPoint PPT PresentationTRANSCRIPT
Institute of Vascular DiseasesClinical Center University of Sarajevo
ESC-ACCP-ACC Guidelines in atherothrombosis
Oštećenje endotela Pro-trombogena površina Aktivirani trombociti Leukociti, makrofagi Oksidacija LDL Vazokonstriktori (EDCF)
Ključni faktori razvoja aterotromboze
• Akutni vaskularni incidenti• Nestabilna angina/non-Q MI• Akutni MI• CVI (trombotski)• Akutna arterijska okluzija• Endovaskularne intervencije • Rekurentni vaskularni incidenti
Aterotromboza
Endotel
ISAR REACT 2
600 mg LD 2 h prior to intervention.
Ključni faktori zaštite krvnog suda
• NO- nitrični oksid• Inhibicija agregacije trombocita• Prostaciklin
GP IIb/IIIa - inhibicija agregacije trombocita
Receptori
Blokiranje (inhibicija) ADP receptora Inhibicija IP3
GP IIb/IIIa molekula oko 50.000
Inhibicija agregacije
• 20 različitih agenasa za inhibiciju agregacije• Inhibicija agregacije mjerena ex vivo nije istovremeno i prevencija aterotromboze• Acetilsalicilna kiselina, dipiridamol i clopidogrel – long-term PO terapija • Abciximab, tirofiban, eptifibatide – kao short-term IV terapija
Antitrombocitni agensi - antiplatelets
• Acetilsalicilna kiselina• Dipiridamol • Thienopyridini (ticlopidine, clopidogrel, prasugrel)• Glycoprotein IIb/IIIa rec. inhibitori (abciximab, tirofiban, eptifibatide)
ADP inhibitori Ticlopidin Clopidogrel Prasugrel
ADP inhibitori
Doziranja ACC/AHA
Stabilna angina 75 mg Nestabilna angina 300 mgAkutni koronarni sindrom 300-600 mgPCI – stent 300-600-900 mgAneurizma aorte 75 mgArterijska okluzivna bolest 75 mgTIA i CVI 75 mg Teška ACC stenoza (dvosudovna bolest) 75 mg Akutni ishemični CVI 75 mg Atrijalna fibrilacija 75 mg
• Uvodna doza (LD)• Optimalna doza (OT)• Održavanje doze (MD)
Doza clopidogrela
Aktivnost clopidogrel-bisulfat
Nema signifikantnu aktivnost in vitro Odlična bioraspoloživost Nakon 2 sata počinje aktivnost u
plazmi 75 mg/dan ostvaruje 40-60% Puni efekat nakon 48-36 sati Ne aficira druge plazma proteine
CAPRIE studijaClopidogrel vs. Aspirin in Patients at Risk of
Ischemic Events
n-19185 Koronarna, cerebralna, i/ili vaskularna
bolest Clopidogrel 75 mg/dan Aspirin 325 mg/dan 8,7% RRR 22,5 mjeseca
CURE studijaClopidogrel in Unstable Angina Reccurent
Events
n-12562 Nestabilna angina MI bez elevacije ST segmenta Clopidogrel + Aspirin Placebo + aspirin 75-325 mg
CHARISMA studijaClopidogrel for High Atherothrombotic Risk
and Ischemic Stabilisation
n-15603 terapija do 42 mjeseca, medijana 28
mjeseci 17% RRR Koronarna, cerebrovaskularna, arterijska
okl., multipli riziko faktori clopidogrel + aspirin vs. aspirin
Uvodna doza
300 – 600 mg Nakon 2 sata aktivnost u plazmi Ostvaruje efekat nakon 6 sati Ne aficira druge plazma proteine
Indikacija
Inhibicija agregacije Antiinflamatorni efekat Clopidogrel 300 – 600 mg/dan, u
kombinaciji sa aspirinom, 24 sata prije intervencije 6 sati prije, 2 sata prije, ili 3 sata
poslije intervencije
Uvodna doza
• ISAR-REACT Study• ISAR-COOL Study • 600 mg clopidogrel • Inhibicija agregacije • Inhibicija inflamacije**
• ISAR-REACT Study (Intracoronary Stenting and Antithrombotic Regimen-Rapid Early Action for Coronary Treatment)
• ISAR-COOL Study (Intracoronary Stenting with Antithrombotic Regimen Cooling-off Trial)
ISAR-REACT Study
ISAR-COOL Study
600 mg inhibicija agregacije + antiinflamatorni efekat
signifikantno izraženiji u odnosu na 300 mg/dan
CREDO MATCH FASTERSPS3ARCH
CLARITY
• High-risk pacijenti
• Produžena terapija - redukcija non-fatal MI,
CVI, ili VD za 25%
Indikacija
• High-risk pacijenti
• Seriuos vascular events (prethodni MI) 36 na 1000 pac. tretiranih 2 godine
Apsolutna redukcija rizika
• High-risk pacijenti
• Seriuos vascular events (prethodni AMI) 38 na 1000 pac. tretiranih 1 mjesec
Apsolutna redukcija rizika
• High-risk pacijenti
• Seriuos vascular events (prethodni CVI ili TIAs) 36 na 1000 pac. tretiranih 2 godine
Apsolutna redukcija rizika
• High-risk pacijenti
• Seriuos vascular events (prethodni akutni CVI) 9 na 1000 pac. tretiranih 1 mjesec
Apsolutna redukcija rizika
• High-risk pacijenti
• Seriuos vascular events (stabilna angina, PAD, AF) 22 na 1000 pac. tretiranih 2 godine
Apsolutna redukcija rizika
1. Reduction of atherosclerotic events (MI, CVI, VD) in pts with recent MI, recent CVI, or established PAD
2. For pts with ACS whether or not PCI (with or without stent) or CABG is performed.
3. Additional use in STEMI treated by fibrinolysis and aspirin, early clopidogrel reduced major events by 20%.
4. Prevention of late post-stent thrombosis after DES should be used 12 months
5. For aspirin resistance
FDA approval - licensed
For AMI, clopidogrel 75 mg daily added to aspirin (75 mg-325 mg once daily) for at least 7 days (Class IA)
Dual antiplatelet therapy for at least 12 month after DES
ACC/AHA guidelines
Non-ST-segment elevation acute coronary syndrome (unstable angina/non-Q-wave MI)
Clopidogrel should be initiated with a single 300 mg loading dose and then continued at 75 mg once daily. Aspirin (75 mg-325 mg once daily) should be initiated and continued in combination with clopidogrel.
ACC/AHA guidelines
For patients with ST-segment elevation acute myocardial infarction, clopidogrel has been shown to reduce the rate of death from any cause and the rate of a combined endpoint of death, re-infarction or stroke
It is not given when urgent CABG is likely
AHA/ACC guidelines
European Society of Cardiology
• post MI, CVI, AOD • clopidogrel 75
mg/day
European Society of Cardiology
• Cardiovascular disease• Multiple risk factors • clopidogrel 75 mg/day
LD 300 or 600 mg. daily MD 75 mg clopidogrela + aspirin 75 mg daily
FDA approval 2007.
Gurbel Pa, Tantry US: Clopidogrel resistance? Thrombosis Res. 2007. 120: 311-321.
Gurbel PA et al. Platelet Reactivity in Patients and Reccurent Events Post-Stenting: Results of PREPARE POST-STENTING Study. J Am Coll.Card. 2005. 46: 1820-1826.
Light transmission aggregometry (LTA)
Vasodilator-stimulated phosphoprotein (VASP)
Non responder or poor responder 5 - 44% patients
Maintenance dose (MD)-Doza održavanja?
150 or 75 mg clopidogrel daily.
van Beckerath N, et al.Eur Heart J. 2007. On-line published. February 1.
TIAnon/cardioembolic stroke
Aspirin, 25 mg aspirina + 2 x 200
dipiridamol Clopidogrel 75 mg dn. Prednost
nad aspirinom (2B) Ako je plasiran stent, aspirin +
clopidogrel
Hvala na pažnji!
CLODIL
(Clopidogrel)