Heparinas e Inibidores da IIb/IIIa nas Síndromes Coronarianas Agudas

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João Pedro Machado Paranhos
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1 Heparinas e Inibidores da IIb/IIIa nas Síndromes Coronarianas Agudas Paulo Caramori, MD, PhD, FSCAI, FACC Serviço de Cardiologia e Centro de Diagnóstico e Terapia Intervencionista Hospital São Lucas PUCRS

2 Síndromes Coronarianas Agudas sem Supra de ST

3 Aterotrombose

4 Prasugrel Ticagrelor

Terapia Adjuvante Impacto do Sangramento Sangramento hospitalar em 34.

5 Terapia Adjuvante Impacto do Sangramento Sangramento hospitalar em pacientes com SCA (OASIS-1/2 +CURE) Eikelboom JW. Circulation 2006;114:774

8 Preditores de Complicações Hemorrágicas Pós-PCI Sangramento / Morbidade: Custo, Internação Prolongada, Transfusões, Isquemia, Óbito IAM < 12 h Gênero Feminino Idosos > 75 anos Peso <60 Kg Administração de IGPIIb/IIIa Duração do Procedimento

9 Preditores de Complicações Hemorrágicas Pós-PCI Mehran R. JACC 2010:

10 Desenho do Estudo ATOLL Randomização o mais cedo possível População do mundo real (incluídos choque e PCR) Sem anticoagulação e sem TT antes Tratamento antiplaquetário = em ambos os grupos n=450 ENOXAPARINA EV 0.5 mg/kg Com ou sem GPIIbIIIa ENOXAPARINA SC IAM-CST ICP Primária 30 dias HNF EV IU com GP IIbIIIa IU sem GP IIbIIIa (Dose ajustada-tca) EP 1 : Óbito, Complicação do IAM, Falha da ICP, Sangramento > EP 2 : Óbito, IAM/SCA recorrente, Revascularização Urgente R ICP Primária HNF EV ou SC n=460 Montalescot G Estocolmo ESC 2010

11 OASIS Study 6-Estudo Design: Randomized, randomizado, Double duplo-cego, Blind, double Double dummy Dummy 12, Patients pacientes with com STEMI IAM supra<12 < h of symptom h de evolução onset Inclusão: Inclusion: ST 2 mm prec der. leads unipolares, or >1 1 mm. limb bipolares leads Exclusão: Exclusion: Contra - ind. p/ for anticoagulant, INR>1.8, gravidez, pregnancy, AVCH<12 ICH<12 mo. Líticos (SK, TPA, TNK, rpa), ATC primária ou não-reperfusão Estratificação Stratification UFH HNF not não-indicada indicated Randomização UFH HNF indicated indicada Randomização Fondaparinux 2.5 mg Placebo Fondaparinux 2.5 mg HNF

12 Desfecho Primary Efficacy primário Outcome eficácia Óbito/IAM Death/MI at dias Days HNF/Placebo Fondaparinux % HR % IC P= Dias

13 Óbito/Reinfarto aos 30 dias % HR=0,79 (0,68-0,92) 14 11,2 HR=0,96 (0,81-1,13) 8,7 8,3 5 PLC HNF 0 FONDA Estrato I FONDA Estrato II

14 Sangramento grave aos 9 dias % HR=0,63 (P=0,06) 1,6 PLC 1 HR=0,95 (P=NS) 1,1 1,1 HNF 0 Estrato I FONDA FONDA Estrato II

15 Global PreAnálises - de subgrupos pré-especificados N HNF/Placebo 11.2% Óbito ou re-iam aos 30 dias Fonda 9.7% Interação P Terapia recanaliz Nenhuma Fibrinolítico ATC primária GRACE risco 0.03 < >= Fonda melhor HNF/ Plac Hazard Ratio melhor

16 Heparinas e Inibidores da IIb/IIIa nas Síndromes Coronarianas Agudas Receita de Bolo Eur Heart J Oct;31(20):

17 Angioplastia Eletiva

Angioplastia Eletiva GPIIb IIIa inhibitors should be used only in bail-out situations (thrombus, slow flow, vessel closure, very complex lesions) UFH: is currently the standard antithrombotic

18 Angioplastia Eletiva GPIIb IIIa inhibitors should be used only in bail-out situations (thrombus, slow flow, vessel closure, very complex lesions) UFH: is currently the standard antithrombotic medication IU/kg i.v. bolus without GPIIb IIIa inhibitors IU/kg with GPIIb IIIa inhibitors Enoxaparin 0.5 or 0.75 mg/kg i.v. bolus STEEPLE trial (NEJM 2006) has suggested a benefit compared with UFH with reduced bleeding hazard but comparable efficacy

19 Angioplastia nas SCASSST

20 Angioplastia nas SCASSST GPIIb IIIa inhibitors should be used in patients with high ischaemic risk undergoing PCI The usefulness of upstream eptifibatide, with or without clopidogrel on board, was not confirmed in EARLY-ACS (NEJM 2009). The lack of benefit was associated with a higher bleeding risk The selective downstream administration of abciximab in the catheterization laboratory, in combination with a 600 mg clopidogrel loading dose, has been shown to be effective in troponin-positive NSTE-ACS (ISAR REACT 2, JAMA 2006) patients and might therefore be preferred over upstream use

21 Angioplastia nas SCASSST Very high ischaemic risk (persistent angina, haemodynamic instability, refractory arrhythmias) immediately referred to the cath lab UFH 60 IU/kg i.v. bolus, followed by infusion until PCI High risk of bleeding: bivalirudin monotherapy with 0.75 mg/kg bolus followed by 1.75 mg/kg/h can be used

22 Angioplastia nas SCASSST Medium-to-high ischaemic risk (troponin positive, recurrent angina, dynamic ST changes) invasive strategy is planned within 24 (-48)h UFH 60 IU/kg i.v. bolus, then infusion until PCI, or Enoxaparin 1 mg/kg subcutaneous (s.c.) bid until PCI, or Fondaparinux 2.5 mg daily s.c. until PCI, or Bivalirudin 0.1 mg/kg i.v. bolus then 0.25 mg/kg/h until PCI In patients 75 years Reduce Enoxaparin to 0.75 mg/kg twice daily until PCI

23 Angioplastia nas SCASSST Low ischaemic risk (troponin negative, no ST-segment changes) Anticoagulation is maintained until PCI Fondaparinux 2.5 mg s.c. daily, or Enoxaparin 1 mg/kg s.c. bid daily (0.75 mg 75 years), or UFH 60 IU/kg i.v. bolus followed by infusion

24 Angioplastia nas SCASSST Management during catheterization UFH: Continue infusion ACT target: s without GPIIb IIIa inhibitors s with GPIIb IIIa inhibitors Enoxaparin less than 8 h since last s.c. application: no additional bolus within 8-12 h of last s.c. application: 0.30 mg/kg i.v. bolus 12 h since last s.c. application: 0.75 mg/kg i.v. bolus Fondaparinux Add UFH IU/kg when PCI is performed

25 Angioplastia no IAM com Supra

26 Angioplastia no IAM com Supra Anticoagulation UFH 60 IU/kg i.v. bolus with GPIIb IIIa inhibitor, or UFH 100 IU/kg i.v. bolus without GPIIb IIIa inhibitor, or Bivalirudin 0.75 mg/kg bolus followed by 1.75 mg/kg/h Antithrombins can be stopped after PCI for STEMI with few exceptions (LV aneurysm / thrombus, AF, prolonged bed rest, deferred sheath removal) Bivalirudin may be preferred in STEMI patients at high risk of bleeding, but thrombotic complications seem to be higher (HORIZONS) Fondaparinux was inferior to UFH in primary PCI (OASIS-6)

Heparinas e Inibidores da IIb/IIIa nas Intervenção Coronária Treatment of CAD patients often requires the combination of antiplatelet and antithrombotic therapies to prevent thrombosis from

27 Heparinas e Inibidores da IIb/IIIa nas Intervenção Coronária Treatment of CAD patients often requires the combination of antiplatelet and antithrombotic therapies to prevent thrombosis from activation of both platelets and the coagulation system. The choice, initiation, and duration of antithrombotic strategies for myocardial revascularization depend on the clinical setting (elective, acute, or urgent intervention) To maximize the effectiveness of therapy and reduce the hazard of bleeding, ischaemic and bleeding risks should be evaluated on an individual basis. A well-validated score for estimating bleeding risk is eagerly awaited.

28 Obrigado! Heparinas e Inibidores da IIb/IIIa nas Síndromes Coronarianas Agudas Paulo Caramori, MD, PhD, FSCAI, FACC Serviço de Cardiologia e Centro de Diagnóstico e Terapia Intervencionista Hospital São Lucas PUCRS

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