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Institute of Vascular Diseases Clinical Center University of Sarajevo

ESC-ACCP-ACC Guidelines in atherothrombosis. Institute of Vascular Diseases Clinical Center University of Sarajevo. Ključni faktori razvoja aterotromboze.

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Institute of Vascular Diseases Clinical Center University of Sarajevo

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  1. ESC-ACCP-ACC Guidelines in atherothrombosis Institute of Vascular DiseasesClinical Center University of Sarajevo

  2. Ključni faktori razvoja aterotromboze Oštećenje endotela Pro-trombogena površina Aktivirani trombociti Leukociti, makrofagiOksidacija LDL Vazokonstriktori (EDCF)

  3. Aterotromboza • Akutni vaskularni incidenti • Nestabilna angina/non-Q MI • Akutni MI • CVI (trombotski) • Akutna arterijska okluzija • Endovaskularne intervencije • Rekurentni vaskularni incidenti

  4. Endotel

  5. ISAR REACT 2 600 mg LD 2 h prior to intervention.

  6. Ključni faktori zaštite krvnog suda • NO- nitrični oksid • Inhibicija agregacije trombocita • Prostaciklin

  7. GP IIb/IIIa - inhibicija agregacije trombocita

  8. Receptori

  9. Blokiranje (inhibicija) ADP receptora Inhibicija IP3

  10. GP IIb/IIIa molekula oko 50.000

  11. Inhibicija agregacije • 20 različitih agenasa za inhibiciju • agregacije • Inhibicija agregacije mjerena ex vivo nije • istovremeno i prevencija aterotromboze • Acetilsalicilna kiselina, dipiridamol i • clopidogrel – long-termPOterapija • Abciximab, tirofiban, eptifibatide – kao • short-term IV terapija

  12. Antitrombocitniagensi - antiplatelets • Acetilsalicilna kiselina • Dipiridamol • Thienopyridini(ticlopidine,clopidogrel, • prasugrel) • Glycoprotein IIb/IIIa rec. inhibitori • (abciximab, tirofiban, eptifibatide)

  13. ADP inhibitori • ADP inhibitori • Ticlopidin • Clopidogrel • Prasugrel

  14. Doziranja ACC/AHA • Stabilna angina 75 mg • Nestabilna angina 300 mg • Akutni koronarni sindrom 300-600 mg • PCI – stent 300-600-900 mg • Aneurizma aorte 75 mg • Arterijska okluzivna bolest 75 mg • TIA i CVI 75 mg • Teška ACC stenoza (dvosudovna bolest) 75 mg • Akutni ishemični CVI 75 mg • Atrijalna fibrilacija 75 mg

  15. Doza clopidogrela • Uvodna doza (LD) • Optimalnadoza (OT) • Održavanje doze (MD)

  16. 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

  17. 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

  18. CURE studijaClopidogrel in Unstable Angina Reccurent Events • n-12562 • Nestabilna angina • MI bez elevacije ST segmenta • Clopidogrel + Aspirin • Placebo + aspirin 75-325 mg

  19. 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

  20. Uvodna doza • 300 – 600 mg • Nakon 2 sata aktivnost u plazmi • Ostvaruje efekat nakon 6 sati • Ne aficira druge plazma proteine

  21. 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

  22. 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)

  23. ISAR-REACT Study ISAR-COOL Study • 600 mg inhibicija agregacije + antiinflamatorni efekat • signifikantno izraženiji u odnosu na 300 mg/dan

  24. CREDO MATCH FASTERSPS3ARCHCLARITY

  25. Indikacija • High-risk pacijenti • Produžena terapija - redukcija non-fatal MI, • CVI, ili VD za 25%

  26. Apsolutna redukcija rizika • High-risk pacijenti • Seriuos vascular events • (prethodni MI) • 36 na 1000 pac. tretiranih 2 godine

  27. Apsolutna redukcija rizika • High-risk pacijenti • Seriuos vascular events • (prethodni AMI) • 38 na 1000 pac. tretiranih 1 mjesec

  28. Apsolutna redukcija rizika • High-risk pacijenti • Seriuos vascular events • (prethodni CVI ili TIAs) • 36 na 1000 pac. tretiranih 2 godine

  29. Apsolutna redukcija rizika • High-risk pacijenti • Seriuos vascular events • (prethodni akutni CVI) • 9 na 1000 pac. tretiranih 1 mjesec

  30. Apsolutna redukcija rizika • High-risk pacijenti • Seriuos vascular events • (stabilna angina, PAD, AF) • 22 na 1000 pac. tretiranih 2 godine

  31. FDA approval- licensed • Reduction of atherosclerotic events (MI, CVI, VD) in pts with recent MI, recent CVI, or established PAD • For pts with ACS whether or not PCI (with or without stent) or CABG is performed. • Additional use in STEMI treated by fibrinolysis and aspirin, early clopidogrel reduced major events by 20%. • Prevention of late post-stent thrombosis after DES should be used 12 months • For aspirin resistance

  32. ACC/AHA guidelines • 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

  33. 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.

  34. AHA/ACC 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

  35. European Society of Cardiology • post MI, CVI, AOD • clopidogrel 75 mg/day

  36. European Society of Cardiology • Cardiovascular disease • Multiple risk factors • clopidogrel 75 mg/day

  37. FDA approval 2007. LD300 or 600 mg. daily MD 75 mg clopidogrela + aspirin 75 mg daily

  38. Non responder or poor responder 5 - 44% patients • 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)

  39. 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.

  40. TIAnon/cardioembolic stroke Aspirin, 25 mg aspirina + 2x200 dipiridamol Clopidogrel 75 mg dn. Prednost nad aspirinom (2B) Ako je plasiran stent,aspirin + clopidogrel

  41. CLODIL (Clopidogrel) Hvala na pažnji!

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