2007 ESC NSTE-ACS 2007 ESC NSTE-ACS GUIDELINESGUIDELINES

CASE 1:

52-y-o man with previous CABG and typical chest pain at rest since 12 hours

CASE 1:

52-y-o man with previous CABG and typical chest pain at rest since 12 hours

CASE 2:

82-y-o woman with hypertension and atypical chest pain at rest 24 h before, now asymptomatic

CASE 1:

52-y-o man with previous CABG and typical chest pain at rest since 12 hours

CASE 2:

82-y-o woman with hypertension and atypical chest pain at rest 24 h before, now asymptomatic

CASE 3:

69-y-o man with diabetes and dyspnea at rest since 48 hours

PrognosisPrognosis

Trends and Prognosis in NSTE-ACSTrends and Prognosis in NSTE-ACS

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100

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Furman MI. et al JACC 2001; 37: 1571-80

Trends and Prognosis in NSTE-ACSTrends and Prognosis in NSTE-ACS

Courtesy A Gitt

0,7

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0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

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STEMI versus NSTEMI STEMI versus NSTEMI Hospital vs 1-Year-Mortality Hospital vs 1-Year-Mortality

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MethodsMethods

MethodsMethods

1- Cost/benefit and cost/risk ratios1- Cost/benefit and cost/risk ratios in the terms of in the terms of – Number Needed to TreatNumber Needed to Treat

2 - Class III re-introduced in the level of recommendations2 - Class III re-introduced in the level of recommendations– Class III = contra-indication (it goes without saying, but Class III = contra-indication (it goes without saying, but

it’s better to say it !)it’s better to say it !)

MethodsMethods

1- Cost/benefit and cost/risk ratios in the form of 1- Cost/benefit and cost/risk ratios in the form of – Number Needed to TreatNumber Needed to Treat

2 - Class III re-introduced2 - Class III re-introduced in the level of recommendationsin the level of recommendations– Class III = contra-indication (it goes without saying, but Class III = contra-indication (it goes without saying, but

it’s better in saying !)it’s better in saying !)

MethodsMethods

3- Quality level of trials taken into account3- Quality level of trials taken into account – Double blind, randomised designDouble blind, randomised design– Use of hard endpoints in the primary endpoint Use of hard endpoints in the primary endpoint

• death and MI death and MI • death / MI / stroke and bleeding as net clinical benefitdeath / MI / stroke and bleeding as net clinical benefit

– Adequate sample size calculationsAdequate sample size calculations– Contemporary adjunctive treatments (stents, clopidogrel, IIb/IIIa Contemporary adjunctive treatments (stents, clopidogrel, IIb/IIIa

inhibitors…)inhibitors…)

4- Efficacy / safety profile of drugs / treatments4- Efficacy / safety profile of drugs / treatments taken into account taken into account for the gradation of recommendationsfor the gradation of recommendations

Classes of RecommendationsClasses of Recommendations Class IClass I Evidence and/or general agreement that a given treatment of Evidence and/or general agreement that a given treatment of

procedure is beneficial, useful, effectiveprocedure is beneficial, useful, effective

Class IIClass II Conflicting evidence and/or a divergence of opinion about the Conflicting evidence and/or a divergence of opinion about the usefulness / efficacy of the given treatment or procedureusefulness / efficacy of the given treatment or procedure

Class IIaClass IIa Weight of evidence / opinion is in favour of usefulness / efficacyWeight of evidence / opinion is in favour of usefulness / efficacy

Class IIbClass IIb Usefulness / efficacy is less well established by evidence / opinionUsefulness / efficacy is less well established by evidence / opinion

Class IIIClass III Evidence or general agreement that the given treatment or procedure Evidence or general agreement that the given treatment or procedure is not useful / effective, and in some cases may be harmful. is not useful / effective, and in some cases may be harmful.

Levels of EvidenceLevels of Evidence

Level of Evidence ALevel of Evidence AData derived from multiple randomized clinical trials or Data derived from multiple randomized clinical trials or

meta-analyses.meta-analyses.

Level of Evidence BLevel of Evidence BData derived from a single randomized clinical trial or Data derived from a single randomized clinical trial or

large non-randomized studies.large non-randomized studies.

Level of Evidence CLevel of Evidence CConsensus of opinion of the experts and/or small studies, Consensus of opinion of the experts and/or small studies,

retrospective studies, registries.retrospective studies, registries.

Diagnosis and risk stratificationDiagnosis and risk stratification

Recommendations for Diagnosis/ Recommendations for Diagnosis/ Risk StratificationRisk Stratification

• Diagnosis and short-term risk stratification of NSTE-ACS should Diagnosis and short-term risk stratification of NSTE-ACS should be based on a combination of clinical history, symptoms, ECG, be based on a combination of clinical history, symptoms, ECG, biomarkers, and risk score results (I-B).biomarkers, and risk score results (I-B).

• The evaluation of the individual risk is a dynamic process that is The evaluation of the individual risk is a dynamic process that is to be updated as the clinical situation evolves.to be updated as the clinical situation evolves.

• A 12-lead ECG should be obtained within 10 min after first A 12-lead ECG should be obtained within 10 min after first medical contact and immediately read by an experienced medical contact and immediately read by an experienced physician (I-C). Additional leads (V3R and V4R, V7–V9) should be physician (I-C). Additional leads (V3R and V4R, V7–V9) should be recorded. ECG should be repeated in the case of recurrence of recorded. ECG should be repeated in the case of recurrence of symptoms, and at 6 and 24 h and before hospital discharge (I-C).symptoms, and at 6 and 24 h and before hospital discharge (I-C).

• Blood must be drawn promptly for troponin (cTnT or cTnI) Blood must be drawn promptly for troponin (cTnT or cTnI) measurement. The result should be available within 60 min (I-C). measurement. The result should be available within 60 min (I-C). The test should be repeated after 6–12 h if the initial test is The test should be repeated after 6–12 h if the initial test is negative (I-A).negative (I-A).

Recommendations for Diagnosis/ Recommendations for Diagnosis/ Risk StratificationRisk Stratification

• Established risk scores (such as GRACE) should be implemented Established risk scores (such as GRACE) should be implemented for initial and subsequent risk assessment (I-B).for initial and subsequent risk assessment (I-B).

• An echocardiogram is recommended to rule in/out differential An echocardiogram is recommended to rule in/out differential diagnoses (I-C).diagnoses (I-C).

• In patients without recurrence of pain, normal ECG findings, and In patients without recurrence of pain, normal ECG findings, and negative troponins tests, a non-invasive stress test for inducible negative troponins tests, a non-invasive stress test for inducible ischaemia is recommended before discharge (I-A).ischaemia is recommended before discharge (I-A).

• The following predictors of long-term death or MI should be The following predictors of long-term death or MI should be considered in risk stratification (I-B).considered in risk stratification (I-B).

• Clinical indicators: age, heart rate, blood pressure, Killip class, Clinical indicators: age, heart rate, blood pressure, Killip class, diabetes, previous MI/CAD; ECG markers: ST-segment diabetes, previous MI/CAD; ECG markers: ST-segment depression; Laboratory markers: troponins, GFR/CrCl/cystatin C, depression; Laboratory markers: troponins, GFR/CrCl/cystatin C, BNP/NT-proBNP, hsCRP; Imaging findings: low EF, main stem BNP/NT-proBNP, hsCRP; Imaging findings: low EF, main stem lesion, threevessel disease; Risk score result.lesion, threevessel disease; Risk score result.

Invasive managementInvasive management

Recommendations for Invasive ManagementRecommendations for Invasive Management

• Urgent coronary angiography is recommended in patients with refractory or Urgent coronary angiography is recommended in patients with refractory or recurrent angina associated with dynamic ST-deviation, heart failure, recurrent angina associated with dynamic ST-deviation, heart failure, lifethreatening arrhythmias, or haemodynamic instability (I-C).lifethreatening arrhythmias, or haemodynamic instability (I-C).

• Early (<72 h) coronary angiography followed by revascularization (PCI or Early (<72 h) coronary angiography followed by revascularization (PCI or CABG) in patients with intermediate to high-risk features is recommended (I-A).CABG) in patients with intermediate to high-risk features is recommended (I-A).

• Routine invasive evaluation of patients without intermediate to high-risk Routine invasive evaluation of patients without intermediate to high-risk features is not recommended (III-C), but non-invasive assessment of inducible features is not recommended (III-C), but non-invasive assessment of inducible ischaemia is advised (I-C).ischaemia is advised (I-C).

• PCI of non-significant lesions is not recommended (III-C).PCI of non-significant lesions is not recommended (III-C).• After critical evaluation of the risk–benefit ratio, and depending on known co-After critical evaluation of the risk–benefit ratio, and depending on known co-

morbidities and potential need for non-cardiac surgery in the short/medium morbidities and potential need for non-cardiac surgery in the short/medium term (e.g. planned intervention or other conditions) requiring temporary term (e.g. planned intervention or other conditions) requiring temporary withdrawal of dual antiplatelet therapy, consideration should be given to the withdrawal of dual antiplatelet therapy, consideration should be given to the type of stent to be implanted (BMS or DES) (I-C).type of stent to be implanted (BMS or DES) (I-C).

TreatmentTreatment--------------

Anti-ischaemic agentsAnti-ischaemic agents

Recommendations for Anti-ischaemic DrugsRecommendations for Anti-ischaemic Drugs• Beta-blockersBeta-blockers are recommended in the absence of are recommended in the absence of

contraindications, particularly in patients with hypertension or contraindications, particularly in patients with hypertension or tachycardia (I-B).tachycardia (I-B).

• Intravenous or oral Intravenous or oral nitratesnitrates are effective for symptom relief in the are effective for symptom relief in the acute management of anginal episodes (I-C).acute management of anginal episodes (I-C).

• Calcium channel blockersCalcium channel blockers provide symptom relief in patients provide symptom relief in patients already receiving nitrates and beta-blockers; they are useful in already receiving nitrates and beta-blockers; they are useful in patients with contraindications to beta-blockade, and in the patients with contraindications to beta-blockade, and in the subgroup of patients with vaso-spastic angina (I-B).subgroup of patients with vaso-spastic angina (I-B).

• Nifedipine, or other dihydropyridines, should not be used unless Nifedipine, or other dihydropyridines, should not be used unless combined with beta-blockers (III-B). combined with beta-blockers (III-B).

TreatmentTreatment--------------

AnticoagulantsAnticoagulants

What’s New with Anti-coagulantsWhat’s New with Anti-coagulants

1 - Pharmacological Treatment1 - Pharmacological Treatment- Superior efficacy with equivalent safety of enoxaparin over UFH - Superior efficacy with equivalent safety of enoxaparin over UFH (Petersen meta-analysis) (Petersen meta-analysis)

- Fondaparinux non-inferior to enoxaparin in OASIS-5- Fondaparinux non-inferior to enoxaparin in OASIS-5

- Fondaparinux reduced bleeding rate by ~ 50% in OASIS-5- Fondaparinux reduced bleeding rate by ~ 50% in OASIS-5

- Reduction in bleeding impacts on outcome (significant risk - Reduction in bleeding impacts on outcome (significant risk reduction for death, MI and stroke)reduction for death, MI and stroke)

2 - Anti-coagulants in the Setting of PCI2 - Anti-coagulants in the Setting of PCI- Enoxaparin is not superior to UFH in SYNERGY- Enoxaparin is not superior to UFH in SYNERGY

- Bivalirudin superior to UFH/LMWH + GPIIb/IIIA - Bivalirudin superior to UFH/LMWH + GPIIb/IIIA inhibitors in ACUITYinhibitors in ACUITY

Anticoagulants – New ComersAnticoagulants – New Comers• FondaparinuxFondaparinux

– Unequivocal benefit over enoxaparinUnequivocal benefit over enoxaparin– Significant RR of both bleeding and ischaemic risksSignificant RR of both bleeding and ischaemic risks– Closes the loop – Shift in the paradigmCloses the loop – Shift in the paradigm– Catheter thrombi issueCatheter thrombi issue– Bleeding risk issue with UFH ‘on top’ of fonda. in PCI patientsBleeding risk issue with UFH ‘on top’ of fonda. in PCI patients

• BivalirudinBivalirudin– Not double blind trialNot double blind trial– Non inferiority margin issueNon inferiority margin issue– Biased comparison of the different regimens Biased comparison of the different regimens – No impact of bleeding risk reduction on outcome at short and long term FUNo impact of bleeding risk reduction on outcome at short and long term FU

Enoxaparin Was Non-Inferior to UFHEnoxaparin Was Non-Inferior to UFHin Reducing Death or MI in the SYNERGY Trialin Reducing Death or MI in the SYNERGY Trial

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JAMA 2004;292:45-54 Am Heart J 2005;149:581-90

0.8

0.85

0.9

0.95

1

Enoxaparin 1 mg sc bidUFH (aPTT 50-70 sec)

Enoxaparinbetter

UFHbetter

Hazard Ratio (95% CI)

0.8 1 1.2

HR 0.96 (0.87-1.06)

30-Day Death/MI30-Day Death/MI

1.1

OASIS 5 TrialOASIS 5 TrialDeath, myocardialDeath, myocardial infarction or refractory ischemia through day 9 infarction or refractory ischemia through day 9

Days

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Haz

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Hazard ratio, 1.01 (95% CI, 0.90 - 1.13)

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0.06

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FondaparinuxEnoxaparin

OASIS 5 TrialOASIS 5 TrialMajor bleeding through day 9Major bleeding through day 9

OASIS 5 TrialOASIS 5 TrialMajor bleeding through day 9Major bleeding through day 9

Days

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Hazard ratio, 0.52 (95% CI, 0.44 - 0.61)P<0.001

0.00

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0.03

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0.01

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FondaparinuxEnoxaparin

Relation Between Bleeding and Mortality in OASIS-5Relation Between Bleeding and Mortality in OASIS-5

NEJM 2006;354:1464

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Estimate P(log rank)

11.7%UFH/Enoxaparin + IIb/IIIa (N=4603)

Bivalirudin + IIb/IIIa (N=4604) 0.8911.8%

Bivalirudin alone (N=4612) 0.01410.1%

Acuity TrialAcuity TrialNet clinical outcome composite end-pointNet clinical outcome composite end-point

Acuity TrialAcuity TrialNet clinical outcome composite end-pointNet clinical outcome composite end-point

Acuity – Primary Endpoint MeasuresAcuity – Primary Endpoint Measures

NEJM 2006;355:2203

Primaryendpoint

0

Net clinicaloutcome

Ischemiccomposite

Majorbleeding

Bivalalone

10.1 %

7.8 %

3.0 %

UFH/Enox+ IIb/IIIa

11.7 %

7.3 %

5.7 %

RR (95% CI)

0.86 (0.77-0.97)

1.08 (0.93-1.24)

0.53 (0.43-0.65)

P value(non inferior)

(superior)

< 0.0010.015

0.020.32

< 0.001< 0.001

Risk Ratio ± 95% CI

0 1 2

UFH/Enoxaparin + GPI vs. Bivalirudin Alone

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UFH/Enox +IIb/IIIa better

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Recommendations for Anticoagulation Recommendations for Anticoagulation (1)(1)

• Anticoagulation is recommended for all patients in addition to Anticoagulation is recommended for all patients in addition to antiplatelet therapy (I-A). antiplatelet therapy (I-A).

• Anticoagulation should be selected according to the risk of both Anticoagulation should be selected according to the risk of both ischaemic and bleeding events (I-B). ischaemic and bleeding events (I-B). Several anticoagulants are Several anticoagulants are available, namely UFH, LMWH, fondaparinux, bivalirudin. The available, namely UFH, LMWH, fondaparinux, bivalirudin. The choice depends on the initial strategy, choice depends on the initial strategy, urgent invasive, early urgent invasive, early invasive, or conservative invasive, or conservative (I-B) (see section Management (I-B) (see section Management Strategy).Strategy).

• In an urgent invasive strategy UFH (I-C), or enoxaparin (IIa-B) or In an urgent invasive strategy UFH (I-C), or enoxaparin (IIa-B) or bivalirudin (I-B) should be immediately started. bivalirudin (I-B) should be immediately started.

Recommendations for Anticoagulation Recommendations for Anticoagulation (2)(2)

• In an non-urgent situation, as long as decision between early In an non-urgent situation, as long as decision between early invasive or conservative strategy is pending :invasive or conservative strategy is pending :

– Fondaparinux is recommended on the basis of the most favorable Fondaparinux is recommended on the basis of the most favorable efficacy/safety profile. (I-A) efficacy/safety profile. (I-A)

– Enoxaparin with a less favourable efficacy/safety profile than Enoxaparin with a less favourable efficacy/safety profile than fondaparinux should be used only if the bleeding risk is low (IIa-B)fondaparinux should be used only if the bleeding risk is low (IIa-B)

– As efficacy/safety profile of LMWH (other than enoxaparin) or UFH As efficacy/safety profile of LMWH (other than enoxaparin) or UFH relative to fondaparinux is unknown; these anticoagulants cannot be relative to fondaparinux is unknown; these anticoagulants cannot be recommended over fondaparinux (IIa-B)recommended over fondaparinux (IIa-B)

Recommendations for Anticoagulation Recommendations for Anticoagulation (3)(3)

• At PCI procedures the initial anticoagulant should be maintained At PCI procedures the initial anticoagulant should be maintained also during the procedure regardless whether this treatment is also during the procedure regardless whether this treatment is UFH (I-C), enoxaparin (IIa-B) or bivalirudin (I-B), while addititional UFH (I-C), enoxaparin (IIa-B) or bivalirudin (I-B), while addititional UFH in standard dose (50-100 IU/kg bolus) is necessary in case of UFH in standard dose (50-100 IU/kg bolus) is necessary in case of fondaparinux (IIa-C). fondaparinux (IIa-C).

• Anticoagulation can be stopped within 24 hours after invasive Anticoagulation can be stopped within 24 hours after invasive procedure (IIa-C). In a conservative strategy, fondaparinux, procedure (IIa-C). In a conservative strategy, fondaparinux, enoxaparin or other LMWH may be maintained up to hospital enoxaparin or other LMWH may be maintained up to hospital discharge (I-B). discharge (I-B).

TreatmentTreatment--------------

Anti-platelet agentsAnti-platelet agents

Anti-Platelet TreatmentAnti-Platelet Treatment

Pharmacological Treatment Pharmacological Treatment

• Loading dose 600mg vs 300mg clopidogrel : unsettled issueLoading dose 600mg vs 300mg clopidogrel : unsettled issue• New ADP receptor antagonists under development (TRITON, New ADP receptor antagonists under development (TRITON,

PLATO, CHAMPION: ongoing studies)PLATO, CHAMPION: ongoing studies)• GP IIb/IIIa inhibitorsGP IIb/IIIa inhibitors

– Upstream or deferredUpstream or deferred– ACUITY Timing – No unequivocal resultsACUITY Timing – No unequivocal results

0.90

0.92

0.94

0.96

0.98

1.00

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Prop

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0.90

0.92

0.94

0.96

0.98

1.00

0 1 2 3 4

0-30 days 31 days to 12 months

PlaceboPlacebo

Clopidogrel

Clopidogrel

RR: 0.79 (0.67-092)p=0.003

RR: 0.82 (0.70-095)P=0.009

CURE TrialCURE TrialEarly and late effects of ClopidogrelEarly and late effects of Clopidogrel

CURE TrialCURE TrialEarly and late effects of ClopidogrelEarly and late effects of Clopidogrel

Days Months

Recommendations for Oral Antiplatelet Drugs (1) Recommendations for Oral Antiplatelet Drugs (1)

• Aspirin is recommended for all patients presenting with NSTE-Aspirin is recommended for all patients presenting with NSTE-ACS without contraindication at an initial loading dose of 160 - ACS without contraindication at an initial loading dose of 160 - 325mg (non-enteric) (I-A), and at a maintenance dose of 75 to 325mg (non-enteric) (I-A), and at a maintenance dose of 75 to 100mg long-term (I-A). 100mg long-term (I-A).

• For all patients, immediate 300mg loading dose of clopidogrel For all patients, immediate 300mg loading dose of clopidogrel is recommended, followed by 75mg clopidogrel daily (I-A). is recommended, followed by 75mg clopidogrel daily (I-A). Clopidogrel should be maintained for 12 months unless there Clopidogrel should be maintained for 12 months unless there is an excessive risk of bleeding (I-A). is an excessive risk of bleeding (I-A).

• For all patients with contraindication to aspirin, clopidogrel For all patients with contraindication to aspirin, clopidogrel should be given instead (I-B).should be given instead (I-B).

Recommendations for Oral Antiplatelet Drugs (2) Recommendations for Oral Antiplatelet Drugs (2)

• In patients considered for an invasive procedure/PCI, In patients considered for an invasive procedure/PCI, a loading dose of 600mg of clopidogrel may be used a loading dose of 600mg of clopidogrel may be used to achieve more rapid inhibition of platelet function to achieve more rapid inhibition of platelet function (IIa-B).(IIa-B).

• In patients pretreated with clopidogrel who need to In patients pretreated with clopidogrel who need to undergo CABG, surgery should be postponed for 5 undergo CABG, surgery should be postponed for 5 days for clopidogrel withdrawal if clinically feasible days for clopidogrel withdrawal if clinically feasible (IIa-C). (IIa-C).

Recommendations for GP IIb/IIIa Inhibitors (1)Recommendations for GP IIb/IIIa Inhibitors (1)• In patients at intermediate to high risk, particularly patients In patients at intermediate to high risk, particularly patients

with elevated troponins, ST-depression, or diabetes, either with elevated troponins, ST-depression, or diabetes, either eptifibatide or tirofiban for initial early treatment are eptifibatide or tirofiban for initial early treatment are recommended in addition to oral antiplatelet agents (IIa-A).recommended in addition to oral antiplatelet agents (IIa-A).

• The choice of combination of antiplatelet agents and The choice of combination of antiplatelet agents and anticoagulants should be made in relation to risk of ischaemic anticoagulants should be made in relation to risk of ischaemic and bleeding events. (I-B)and bleeding events. (I-B)

• Patients who received initial treatment with eptifibatide or Patients who received initial treatment with eptifibatide or tirofiban prior to angiography, should be maintained on the tirofiban prior to angiography, should be maintained on the same drug during and after PCI (IIa-B) same drug during and after PCI (IIa-B)

Recommendations for GP IIb/IIIa Inhibitors (2)Recommendations for GP IIb/IIIa Inhibitors (2)

• In high risk patients not pretreated with GP IIb/IIIa inhibitors and In high risk patients not pretreated with GP IIb/IIIa inhibitors and proceeding to PCI, abciximab is recommended immediately following proceeding to PCI, abciximab is recommended immediately following angiography. angiography. (I-A) The use of eptifibatide or tirofiban in this setting is (I-A) The use of eptifibatide or tirofiban in this setting is less well established (IIa-B). less well established (IIa-B).

• GP IIb/IIIa inhibitors must be combined with an anticoagulant (I-A).GP IIb/IIIa inhibitors must be combined with an anticoagulant (I-A).

• Bivalirudin may be used as an alternative to GP IIb/IIIa inhibitors plus Bivalirudin may be used as an alternative to GP IIb/IIIa inhibitors plus UFH/LMWH. (IIa-B) UFH/LMWH. (IIa-B)

• When anatomy is known and PCI planned to be performed within 24 When anatomy is known and PCI planned to be performed within 24 hours with GP IIb/IIIa inhibitors, most secure evidence is for abciximab hours with GP IIb/IIIa inhibitors, most secure evidence is for abciximab (IIa-B)(IIa-B)

Recommendations for Resistance to Antiplatelet Recommendations for Resistance to Antiplatelet Treatment/Drugs InteractionsTreatment/Drugs Interactions

• Routine assessment of platelet aggregation inhibition in patients Routine assessment of platelet aggregation inhibition in patients submitted to either aspirin or clopidogrel therapy, or both, is not submitted to either aspirin or clopidogrel therapy, or both, is not recommended (IIb-C).recommended (IIb-C).

• NSAID (selective COX 2 inhibitors and non-selective NSAID) NSAID (selective COX 2 inhibitors and non-selective NSAID) should not be administered in combination with either aspirin or should not be administered in combination with either aspirin or clopidogrel (III-C).clopidogrel (III-C).

• Clopidogrel can be administered with all statins (I-B).Clopidogrel can be administered with all statins (I-B).

• The triple association of aspirin, clopidogrel and VKA should only The triple association of aspirin, clopidogrel and VKA should only be given if compelling indication exists, in which case, the lowest be given if compelling indication exists, in which case, the lowest efficacious INR and shortest duration for the triple association efficacious INR and shortest duration for the triple association should be targeted (IIa-C). should be targeted (IIa-C).

Recommendations for Withdrawal of Recommendations for Withdrawal of Antiplatelet TreatmentAntiplatelet Treatment

• Temporary interruption of dual antiplatelet therapy (aspirin and Temporary interruption of dual antiplatelet therapy (aspirin and clopidogrel) within the first 12 months after the initial episode is clopidogrel) within the first 12 months after the initial episode is discouraged (I-C). discouraged (I-C).

• Temporary interruption for major or life-threatening bleeding or for Temporary interruption for major or life-threatening bleeding or for surgical procedures where even minor bleeding may result in severe surgical procedures where even minor bleeding may result in severe consequences (brain or spinal surgery) is mandatory (IIa-C).consequences (brain or spinal surgery) is mandatory (IIa-C).

• Prolonged or permanent withdrawal of aspirin, clopidogrel or both is Prolonged or permanent withdrawal of aspirin, clopidogrel or both is discouraged unless clinically indicated. Consideration should be discouraged unless clinically indicated. Consideration should be given to the risk of recurrence of ischaemic events which depends given to the risk of recurrence of ischaemic events which depends (among other factors), on initial risk, on presence and type of stent (among other factors), on initial risk, on presence and type of stent implanted, and on time window between proposed withdrawal and implanted, and on time window between proposed withdrawal and index event and/or revascularisation (I-C).index event and/or revascularisation (I-C).

Clinical Use of Antithrombotic Therapy.Clinical Use of Antithrombotic Therapy. Oral Antiplatelet TherapyOral Antiplatelet Therapy

Aspirin initial dose: 160–325 mg nonenteric formulation, followed by 75–100mg dailyAspirin initial dose: 160–325 mg nonenteric formulation, followed by 75–100mg dailyClopidogrel 75 mg/d after a loading dose of 300mg (600mg when rapid onset of action is wanted)Clopidogrel 75 mg/d after a loading dose of 300mg (600mg when rapid onset of action is wanted)

Anticoagulants Anticoagulants

Fondaparinux* 2.5mg subcutaneously dailyFondaparinux* 2.5mg subcutaneously dailyEnoxaparin* 1mg/kg subcutaneously every 12 h Enoxaparin* 1mg/kg subcutaneously every 12 h Dalteparin* 120 IU/kg every 12 hDalteparin* 120 IU/kg every 12 hNadroparin* 86 IU/kg every 12 hNadroparin* 86 IU/kg every 12 hUFH intravenous Bolus 60–70 U/kg (maximum 5000 IU) followed by infusion of 12–15 IU/kg/h (maximum 1000 U/h) UFH intravenous Bolus 60–70 U/kg (maximum 5000 IU) followed by infusion of 12–15 IU/kg/h (maximum 1000 U/h)

titrated to aPTT 1.5–2.5 times controltitrated to aPTT 1.5–2.5 times control•Bivalirudin* intravenous bolus of 0.1 mg/kg and infusion of 0.25 mg/kg/hr. Additional intravenous bolus 0.5 mg/kg Bivalirudin* intravenous bolus of 0.1 mg/kg and infusion of 0.25 mg/kg/hr. Additional intravenous bolus 0.5 mg/kg

and infusion increased to 1.75 mg/kg/hour before PCIand infusion increased to 1.75 mg/kg/hour before PCI

GP IIb/IIIa inhibition*GP IIb/IIIa inhibition*

Abciximab 0.25 mg/kg intravenous bolus followed by infusion of 0.125 µg/kg/min (maximum 10 µg/min) for 12 to Abciximab 0.25 mg/kg intravenous bolus followed by infusion of 0.125 µg/kg/min (maximum 10 µg/min) for 12 to 24 h24 h

Eptifibatide 180 µg/kg intravenous bolus (second bolus after 10 min for PCI) followed by infusion of 2.0 µg/kg/min Eptifibatide 180 µg/kg intravenous bolus (second bolus after 10 min for PCI) followed by infusion of 2.0 µg/kg/min for 72 to 96 hfor 72 to 96 h

•Tirofiban 0.4 µg/kg/min intravenously for 30 minutes followed by infusion of 0.10 µg/kg/min for 48 to 96 h. A high Tirofiban 0.4 µg/kg/min intravenously for 30 minutes followed by infusion of 0.10 µg/kg/min for 48 to 96 h. A high dose regimen (bolus 25µg/kg + 0.15µg/kg/min infusion for 18 hours) is tested in clinical trials.dose regimen (bolus 25µg/kg + 0.15µg/kg/min infusion for 18 hours) is tested in clinical trials.

TreatmentTreatment--------------

StatinsStatins

Recommendations for Statins in NSTE-ACSRecommendations for Statins in NSTE-ACS

• Statins are recommended for all NSTE-ACS patients (in the Statins are recommended for all NSTE-ACS patients (in the absence of contraindications), irrespective of cholesterol levels, absence of contraindications), irrespective of cholesterol levels, initiated early (within 1–4 days) after admission, with the aim of initiated early (within 1–4 days) after admission, with the aim of achieving LDLc levels <100 mg/dL (<2.6 mmol/L) (I-B).achieving LDLc levels <100 mg/dL (<2.6 mmol/L) (I-B).

• Intensive lipid-lowering therapy with target LDLc levels <70 mg/dL Intensive lipid-lowering therapy with target LDLc levels <70 mg/dL (<1.81 mmol/L) initiated within 10 days after admission is (<1.81 mmol/L) initiated within 10 days after admission is advisable (IIa-B).advisable (IIa-B).

Invasive vs Cons 7962

10 102 11 1010

20.5 215%0% 10% 0.50.1 2 1012.5%0% 5%

Odds ratio and 95% CI NNT and 95% CI Odds ratio and 95% CIIncidence Incidence

Death or MISize Major bleeds

Exp+ Ctrl+ Exp+ Ctrl+ Exp+ Ctrl+

DTI vs UFH 24701

LMWH vs UFH 21946

GP IIb/IIIa vs Ctrl 31402

Heparin vs Ctrl 2858

Aspirin vs Ctrl 3096

15%

0.84

0.88

0.91

0.91

0.55

0.47

63

102

113

111

31

17

1.3

1.1

1.6

2.3

1.4

NSTE-ACS –NSTE-ACS – Summary of Treatment ApproachesSummary of Treatment Approaches

Primary therapeutic measuresPrimary therapeutic measures

CASE 1:

52-y-o man with previous CABG and typical chest pain at rest since 12 hours

CASE 1:

52-y-o man with previous CABG and typical chest pain at rest since 12 hours

CASE 2:

82-y-o woman with hypertension and atypical chest pain at rest 24 h before, now asymptomatic

CASE 1:

52-y-o man with previous CABG and typical chest pain at rest since 12 hours

CASE 2:

82-y-o woman with hypertension and atypical chest pain at rest 24 h before, now asymptomatic

CASE 3:

69-y-o man with diabetes and dyspnea at rest since 48 hours

More on statins in NSTEACSMore on statins in NSTEACS

…but remember our recommended …but remember our recommended reading…reading…

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