Antithrombotic treatment in ACS: what do the guidelines say? Nicolas Danchin, HEGP, Paris France

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1 Antithrombotic treatment in ACS: what do the guidelines say? Nicolas Danchin, HEGP, Paris France

2 Disclosures Research grants: Astra-Zeneca, Merck, Novartis, Pfizer, sanofi-aventis, Servier, The MedCo Fees for giving lectures and/or consulting: Astra-Zeneca, BMS, Boehringer-ngelheim, GSK, Lilly, Menarini, MSD-Schering, Novartis, Novo, Pfizer, sanofi-aventis, Servier, The MedCo

3 NSTE-ACS

4 ESC guidelines 2011: Risk stratification Diagnosis and short-term ischemic/bleeding risk stratification of NSTE-ACS should be based on a combination of clinical history, symptoms, physical findings, ECG, biomarkers. The use of established risk scores is recommended. Best care for ACS patients is provided in specialised chest pain units.

5 Recommendations for oral antiplatelet agents Aspirin should be given to all patients without contraindication at an initial loading dose of mg, and a maintenance dose of mg daily long-term, regardless of treatment strategy The combination of aspirin with NSAD (selective COX-2 inhibitors and non-selective NSAD) is not recommended A P2Y12 inhibitor should be added to aspirin as soon as possible and maintained over 12 months, unless there are contraindications such as excessive risk of bleeding Ticagrelor (180 mg loading dose, 90 mg twice daily) is recommended for all patients at moderate to high risk of ischaemic events (e.g. elevated troponins), regardless of initial treatment strategy and including those pretreated with clopidogrel (which should be discontinued when ticagrelor is commenced) Prasugrel (60 mg loading dose, 10 mg daily dose) is recommended for P2Y12 naïve patients in whom coronary anatomy is known and who are proceeding to PC unless there is a high risk of lifethreatening bleeding or other contraindications Class Level A C A B B

6 Recommendations for oral antiplatelet agents Clopidogrel (300 mg loading dose, 75 mg daily) is recommended in patients who cannot receive ticagrelor or prasugrel A 600 mg loading dose of clopidogrel (or a supplementary 300 mg dose at PC following an initial 300 mg loading dose) is recommended for patients scheduled for an invasive strategy when ticagrelor or prasugrel is not an option A higher maintenance dose of clopidogrel 150 mg daily should be considered for the first 7 days in patients managed with PC and without increased risk of bleeding ncreasing the maintenance dose of clopidogrel based on platelet function testing is not advised as routine but may be considered in selected cases A PP (preferably not omeprazole) in combination with DAPT is recommended in patients with a history of G haemorrhage or peptic ulcer, and appropriate patients with multiple other risk factors (Helicobacter pylori infection, age 65 years, concurrent use of anticoagulants and steroids) Genotyping and/or platelet function testing may be considered in selected cases when clopidogrel is used Class a b b Level A B B B A A

7 Recommendations for oral antiplatelet agents Prolonged or permanent withdrawal of P2Y12 inhibitors within 12 months after the index event is discouraged unless clinically indicated n patients pre-treated with P2Y12 inhibitors who need to undergo non-emergent major surgery (including CABG), postponing surgery at least for 5 days after cessation of ticagrelor or clopidogrel, and 7 days for prasugrel, if clinically feasible and unless the patient is at high risk of ischaemic events, should be considered Ticagrelor or clopidogrel should be considered to be (re-)started after CABG surgery as soon as considered safe Class a a Level C C B

8 Recommendations for GP b/a inhibitors The choice of combination of oral antiplatelet agents, a GP b/a receptor inhibitor, and anticoagulants should be made in relation to the risk of ischaemic and bleeding events Among patients who are already treated with DAPT, the addition of a GP b/a receptor inhibitor for high-risk PC (elevated troponin, visible thrombus) is recommended if the bleeding risk is low Eptifibatide or tirofiban added to ASA should be considered prior to angiography in high risk patients when loading with P2Y12 inhibitors is not feasible n high risk patients, eptifibatide or tirofiban may be considered prior to early angiography in addition to DAPT, is there is ongoing ischaemia and the risk of bleeding is low GP b/a receptor inhibitors are not recommended routinely before angiography in an invasive treatement strategy GP b/a receptor inhibitors are not recommended for patients on DAPT who are treated conservatively Class a b Level C B C C A A

9 ACC/AHA 2011 guidelines Choice of second antiplatelet agent: class General situation: Clopidogrel (B) or GPb/a inhibitors (A) (eptifibatde or tirofiban) At the time of PC Clopidogrel if not started before (A) or Prasugrel (B) or GPb/a inhibitor (A) f initial conservative strategy: Clopidogrel (B) for 1 month and ideally up to 1 year

10 ACC/AHA 2011 guidelines Class b f conservative strategy used, eptifibatide/tirofiban may be reasonable (B) Prasugrel 60mg may be considered prior to CAG, if bleeding risk low and need for CABG unlikely (C) Upstream GPb/a inhibitors may be considered on top of ASA+thienopyridine in high-risk patients selected for invasive strategy and not at high bleeding risk (B) n patients undergoing PC, a 600 mg loading dose of clopidogrel followed by 150 mg for 6 days, then 75 mg may be reasonable if bleeding risk not high (B). Platelet function testing in patients on a thienopyridine may be reasonable if results are likely to alter management (B) Genotyping in patients on clopidogrel may be considered if results are likely to alter management (C)

11 ACC/AHA 2011 guidelines Class Class, no benefit: Abciximab should not be administered when PC not planned Upstream GPb/a inhibitors should not be used in patients receiving ASA + thienopyridine if ischemic risk low or bleeding risk high Class, harm: Prasugrel potentially harmful in patients with a prior history of TA/stoke for whom PC is planned

12 Recommendations for anticoagulants Class Anticoagulation is recommended for all patients in addition to antiplatelet therapy A The anticoagulation should be selected according to both ischaemic and bleeding risks, and according to the efficacy/safety profile of the chosen agent Fondaparinux (2.5 mg subcutaneously daily) is recommended as having the most favourable efficacy-safety profile with respect to anticoagulation f the initial anticoagulant is fondaparinux, a single bolus of of UFH (85 U/Kg adapted to ACT, or 60 U in case of concomitant use of GPb/a receptor inhibitors) should be added at the time of PC Enoxaparin (1 mg twice daily) can be considered in patients with low bleeding risk B f fondaparinux or enoxaparin are not available, UFH with a target aptt of 50-70s or other LMWHs at the psecific recommended doses are indicated Bivalirudin plus provisional GPb/a inhibitors is recommended as an alternative to UFH plus GPb//a receptor inhibitors in patients with an intended urgent or early invasive strategy, particularly in patients with a high bleeding risk n a purely conservative strategy, anticoagulation should be maintained up to hospital discharge Level C A B C B A

13 Recommendations for anticoagulants Discontinuation of anticoagulation should be considered after an invasive procedure unless otherwise indicated Class A cross-over of heparins (UFH and LMWH) is not recommedned B a Level C

14 ESC 2011: Specific situations Recommendations for anaemia Recommendations for CKD

15 STEM

16 ESC 2008; ESC 2010 Reperfusion strategy

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19 Revascularised STEM : antiplatelet agents Class Level of evidence ASA B Clopidogrel (with 600 mg loading dose ASAP) C Prasugrel B Ticagrelor B + GP b-a antagonists (in patients with evidence of high intracoronary thrombus burden) Abciximab a A Eptifibatide a B Tirofiban b B Upstream GP b-a antagonists B "The controversial literature data, the negative outcome of the only prospective RCT, and the beneficial effects of faster acting and more efficacious ADP ESC/EACTS 2010 receptor blockers in primary PC do not support pre-hospital or pre-catheterization use of GPb a inhibitors."

20 Revascularised STEM : anticoagulants Class Level of evidence Bivalirudin (monotherapy) B UFH C Fondaparinux B ESC 2010 revascularisation guidelines

21 Clopidogrel recommended for 12 months

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26 Conclusion There is still no universal reference for antithrombotic regimen, both in STEM and NSTE-ACS patients. The optimal combination of antiplatelet and anticoagulant agents should take into account: ischemic events risk bleeding risk initial strategy chosen