Institute of Vascular Diseases Clinical Center University of Sarajevo

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)