5.1. Antiplaquettaire : acide acétylsalicylate (AAS)
GPC
AHA 2013 (QM) ESC 2012 (QM) NICE 2013 (QB) AUS (QM)
Class I
1. Aspirin (162- to 325-mg loading dose) and clopidogrel (300-mg loading dose for patients ≤75 years of age, 75-mg dose for patients
>75 years of age) should be administered to patients with STEMI who receive fibrinolytic therapy.(Level of Evidence: A)
2. Aspirin 81 to 325 mg daily should be continued indefinitely(Level of Evidence: A) and clopidogrel (75 mg daily) should be continued for at least 14 days (Level of Evidence: A) and up to 1 year (Level of Evidence: C) in patients with STEMI who receive fibrinolytic therapy.
Class IIa
1. It is reasonable to use aspirin 81 mg per day in preference to higher maintenance doses after fibrinolytic therapy. (Level of Evidence: B)
The beneficial effects of aspirin and clopidogrel with fibrinolytic therapy are well established. These agents should be given before or with the fibrinolytic.The recommendation that clopidogrel be continued for up to 1 year is extrapolated from the experience with DAPT in patients with non–ST-elevation ACS. The coadministration of other P2Y12 antagonists with fibrinolytic therapy has not been prospectively studied.
Oral or i.v. aspirin must be administered. I B With fibrinolytic therapy
• Aspirin Starting dose 150–
500 mg orally or i.v. dose of 250 mg if oral ingestion is not possible.
Antiplatelet therapy with low dose aspirin (75–100 mg) is indicated indefinitely after STEMI. I A
In patients who are intolerant to aspirin, clopidogrel is indicated as an alternative to aspirin. I B
Offer aspirin to all people after an MI and continue it indefinitely, unless they are aspirin intolerant or have an indication for anticoagulation
Offer aspirin to people who have had an MI more than 12 months ago and continue it indefinitely.
For patients with aspirin hypersensitivity, clopidogrel monotherapy should be considered as an alternative treatment.
Aspirin 300 mg orally initially (dissolved or chewed) followed by 100–150 mg/day is recommended for all patients with ACS in the absence of hypersensitivity. Strong IA
Discharge management and secondary prevention
Aspirin (100–150 mg/day) should be continued indefinitely unless it is not tolerated or an indication for anticoagulation becomes apparent. Strong IA Clopidogrel should be prescribed if aspirin is contraindicated or not tolerated.Strong IA
Practice advice
Enteric-coated aspirin preparations and concurrent prescription of proton-pump inhibitors (PPI) should be considered in patients at increased risk of upper gastrointestinal bleeding, especially when aspirin is prescribed in combination with other antiplatelet agents and anticoagulants.The use of enteric-coated preparations should be avoided at the time of emergency presentations due to delayed gastrointestinal (GI) absorption.
5.2. Antiplaquettaire : clopidogrel
GPC
AHA 2013 (QM) ESC 2012 (QM) NICE 2013 (QB) AUS (QM)
Class I
1. clopidogrel (300-mg loading dose for patients ≤75 years of age, 75-mg dose for patients >75 years of age) should be administered to patients with STEMI who receive fibrinolytic therapy.(Level of Evidence: A) 2. clopidogrel (75 mg daily) should be
continued for at least 14 days(Level of Evidence: A) and up to 1 year (Level of Evidence: C) in patients with STEMI who receive fibrinolytic therapy.
Clopidogrel is indicated in addition to aspirin.I,A With fibrinolytic therapy
• Clopidogrel Loading dose of 300 mg orally if aged ≤75 years, followed by a maintenance dose of 75 mg/day.
In the CLopidogrel as Adjunctive Reperfusion Therapy–Thrombolysis In Myocardial Infarction 28 (CLARITY-TIMI 28) trial, clopidogrel added to aspirin reduced the risk of cardiovascular events in patients
≤75 years of age who had been treated with fibrinolysis, and in the Clopidogrel and Metoprolol in Myocardial Infarction Trial (COMMIT), clopidogrel reduced overall mortality in such patients.
Accordingly, there is a good case for the routine use of clopidogrel added to aspirin as an adjunct to lytic therapy. Prasugrel and ticagrelor have not been studied as adjuncts to fibrinolysis and should not be given.
Offer clopidogrel as a treatment option for at least 1 month and consider continuing for up to 12 months to: People who have had a STEMI and medical management with or without
reperfusion treatment with a fibrinolytic agent.
Antiplatelet therapy: For fibrinolytic-treated patients, clopidogrel (300 mg loading dose and 75 mg per day) is recommended at the time of fibrinolytic therapy. Currently, the safety and efficacy of ticagrelor or prasugrel has not been studied in conjunction with fibrinolysis (i.e.
within 24 hours of fibrinolytic therapy).
DOCUMENTS CANADIENS
SCC 2004 ET SCC 2009 RQCT 2009
In STEMI patients undergoing reperfusion with fibrinolysis, evidence supports the acute administration of ASA as well as clopidogrel delivered as a 300 mg loading dose in patients younger than 75 years of age and only 75 mg in those 75 years of age and older. Although information regarding the optimal duration of therapy in the STEMI population is absent, based on extrapolation of data from non-ST elevation acute coronary syndromes and PCI patients, it is expected that further benefit would be obtained through administration of dual antiplatelet therapy over the long term, probably for a duration of one year.
Que 300 mg de clopidogrel soient administrés à tous les patients avec diagnostic d’IAMEST à l’exception des patients de plus de 75 ans, en plus de l’ASA, dès la confirmation par l’ECG préhospitalier;
5.3. Anticoagulant : choix de traitement
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AHA 2013 (QM) ESC 2012 (QM) NICE 2013
(QB) AUS (QM) MONOGRAPHIE CANADIENNE
Class I
a. UFH administered as a weight-adjusted intravenous bolus and infusion to obtain an activated partial thromboplastin time of 1.5 to 2.0 times control, for 48 hours or until revascularization (Level of Evidence: C);
b. Enoxaparin administered according to age, weight, and creatinine clearance, given as an intravenous bolus, followed in 15 minutes by subcutaneous injection for the duration of the index hospitalization, up to 8 days or until
revascularization (Level of Evidence: A); or
c. Fondaparinux administered with initial intravenous dose, followed in 24 hours by daily subcutaneous injections if the estimated creatinine clearance is greater than 30 mL/min, for the duration of the index hospitalization, up to 8 days or until revascularization.(Level of Evidence: B)
Dosing of UFH is predicated on the activated partial thromboplastin time, and monitoring of platelet counts to avoid the risks of excess bleeding and heparin-induced thrombocytopenia (HIT) is advised. UFH may be given as an intravenous bolus and infusion for patients receiving streptokinase if they are at high risk for systemic embolization. Enoxaparin is preferred over UFH for anticoagulation extending beyond 48 hours. Caution is advised when enoxaparin is administered to patients with impaired renal function.Fondaparinux should not be given as the sole anticoagulant to patients referred for PCI and is contraindicated for patients with a creatinine clearance <30 mL/min. Bivalirudin may be used for patients treated with a fibrinolytic agent who develop HIT and require continued anticoagulation.
Anticoagulation is recommended in STEMI patients treated with lytics until revascularization (if performed) or for the duration of hospital stay up to 8 days. The anticoagulant can be: I A
• Enoxaparin i.v followed by s.c. (using the regimen described below) (preferred over UFH). I A
• UFH given as a weight-adjusted i.v. bolus and infusion. I C
In patients treated with streptokinase, fondaparinux i.v.
bolus followed by s.c. dose 24 h later. IIa B
In spite of an increased risk of major bleeding, the net clinical benefit favoured enoxaparin over UFH in more recent studies: in the ASsessment of the Safety and Efficacy of a New Thrombolytic 3 (ASSENT 3) trial (n = 6095), a standard dose of enoxaparin given in association with tenecteplase for a maximum of 7 days reduced the risk of in-hospital reinfarction or in-hospital refractory ischaemia when compared with UFH.Enoxaparin was associated with a reduction in the risk of death and reinfarction at 30 days when compared with a weight-adjusted UFH dose, but at the cost of a significant increase in non-cerebral bleeding complications. The net clinical benefit (absence of death, non-fatal infarction and intracranial haemorrhage) favoured enoxaparin.
When treating
Either unfractionated heparin or enoxaparin is
recommended in patients with ACS at intermediate to high risk of ischaemic events.
Strong IA
Adjunctive Pharmacotherapy Antithrombin therapy:
Enoxaparin is recommended over unfractionated heparin Choice Between Indirect Thrombin Inhibitors.
Enoxaparin may be preferred over UFH as it does not require activated partial
thromboplastin time (aPTT) monitoring and is simpler to administer. Swapping between enoxaparin and UFH has been shown to increase bleeding risk and is not recommended.
Données démographiques et plan de l’essai [XRP4563B/3001 ExTRACT-TIMI 25] Au cours d’une étude multicentrique menée à double insu, avec double placebo et groupes parallèles (XRP4563B/3001 ExTRACT-TIMI 25), des patients ayant souffert d’un infarctus aigu du myocarde avec sus-décalage du segment ST (STEMI) qui étaient admissibles à un traitement par un fibrinolytique ont été randomisés dans une proportion de 1:1 en vue de recevoir LOVENOX ou de l’héparine non fractionnée.
Résultats de l’essai Le paramètre d’efficacité principal était composé du décès toutes causes confondues et de l’infarctus du myocarde récidivant dans les 30 jours suivant la randomisation
Les données relatives à l’efficacité, qui sont présentées ci-dessous, indiquent que la fréquence du paramètre d’efficacité principal (décès ou infarctus du myocarde récidivant) a été de 9,9 % dans le groupe énoxaparine, comparativement à 12,0 % dans le groupe héparine non fractionnée, ce qui correspond à une réduction de l’ordre de 2,1 % du risque absolu et de 17 % (p < 0,001) du risque relatif.
5.4. Anticoagulant : durée du traitement
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AHA 2013 (QM) ESC 2012 (QM) NICE 2013 (QB)
5.5. Anticoagulant : héparine non fractionnée
GPC
AHA 2013 (QM) ESC 2012 (QM) NICE 2013 (QB)
UFH administered as a weight-adjusted IV bolus and infusion to obtain an activated partial thromboplastin time of 1.5 to 2.0 times control, for 48 hours or until revascularization. IV bolus of 60 U/kg (maximum 4000 U) followed by an infusion of 12 U/kg/h (maximum 1000 U) initially, adjusted to maintain aPTT at 1.5 to 2.0 times control (approximately 50 to 70 s) for 48 h or until revascularization. (Level of Evidence: C);
Dosing of UFH is predicated on the activated partial thromboplastin time, and monitoring of platelet counts to avoid the risks of excess bleeding and heparin-induced thrombocytopenia (HIT) is advised. UFH may be given as an intravenous bolus and infusion for patients receiving streptokinase if they are at high risk for systemic embolization.
Unfractionated heparin 60 U/kg i.v. bolus with a maximum of 4000 U followed by an i.v. infusion of 12 U/kg with a maximum of 1000 U/h for 24–48 h.Target aPTT: 50–70 s or 1.5 to 2.0 times that of control to be monitored at 3, 6, 12 and 24 h.
Careful dosing and close monitoring of i.v. UFH therapy is mandatory ; aPTT values >70 s are associated with a higher likelihood of bleeding, reinfarction and death.
Heparin (an anticoagulant) is given with all of the thrombolytic drugs except streptokinase. It is usually administered as an IV bolus injection before thrombolysis, followed by an IV infusion. When given with tenecteplase the heparin dose is weight adjusted.
5.6. Anticoagulant : héparine de faible poids moléculaire (HFPM)
GPC MONOGRAPHIES APES
AHA 2013 (QM) ESC 2012 (QM) AUS (QM) MONOGRAPHIE CANADIENNE MONOGRAPHIE ÉTATS-UNIENNE Guide de l’usage optimal des HFPM pour les patients obèses et insuffisants rénaux Enoxaparin
administered according to age, weight, and creatinine clearance, given as an intravenous bolus, followed in 15 minutes by subcutaneous injections for the duration of the index followed in 15 min by 1 mg/kg followed 15 min later by 1 mg/kg s.c. every 12 h until hospital discharge for a maximum of 8 days The first two doses should not exceed 100 mg. In patients >75 years of age: no i.v. bolus; start with first s.c. dose of 0.75 mg/kg with a maximum of 75 mg for the first two s.c.
doses. In patients with creatinine clearance of <30 mL/min, regardless of age, the s.c. doses are
Patients Receiving Fibrinolysis for STEMI.
Enoxaparin with a 30 mg IV bolus (<75 years) and then 1 mg/kg SC dose should be 0.75 mg/kg SC BD with no IV bolus.
Enoxaparin in Patients With CKD. Enoxaparin should be dosed as 1 mg/kg daily in patients with CKD stage 4, and is not
recommended in CKD stage 5. No
Traitement de l’infarctus aigu du myocarde avec sus-décalage du segment ST Chez les patients ayant subi un infarctus aigu du myocarde avec sus-décalage du segment ST, la posologie recommandée pour LOVENOX est de 1 bolus i.v. de 30 mg, suivi immédiatement d’une dose de 1 mg/kg par voie s.-c.
toutes les 12 heures (maximum de 100 mg dans le cas de chacune des 2 premières doses s.-c. seulement, les doses subséquentes étant de 1 mg/kg s.-c.). Pour connaître la posologie recommandée chez les patients âgés de ≥ 75 ans, consulter la section «Personnes âgées» ci-dessous. Lorsqu’il est administré en association avec un thrombolytique (fibrino-spécifique ou non), LOVENOX doit être injecté de 15 minutes avant à 30 minutes après le traitement fibrinolytique. Dès que le diagnostic d’infarctus aigu du myocarde avec sus-décalage du segment ST est établi, on doit systématiquement
administrer de l’acide acétylsalicylique (AAS) à tous les patients et poursuivre le traitement à raison de 75 à 325 mg, 1 f.p.j., à moins de contre-indication. On recommande d’administrer le traitement par LOVENOX durant 8 jours ou jusqu’à l’obtention du congé de l’hôpital, selon la première éventualité.
Personnes âgées (≥ 75 ans) Pour le traitement de l’infarctus aigu du myocarde avec sus-décalage du segment ST chez les patients âgés de ≥ 75 ans, on ne doit pas administrer un bolus i.v. initial. Le traitement doit être amorcé à raison de 0,75 mg/kg s.-c. toutes les 12 heures (maximum de 75 mg dans le cas de chacune des 2 premières doses s.-c. seulement, les
In patients with acute ST-segment elevation MI (STEMI) who are younger than 75 years of age, an initial direct ("bolus") IV injection
ofenoxaparinsodium 30 mg plus a 1-mg/kg subcutaneous dose is recommended by the manufacturer, followed yenoxaparinsodium 1 mg/kg every 12 hours by subcutaneous injection; a maximum of 100 mg is recommended for each of the first 2 subcutaneous doses.A reduced dosage, without an initial IV dose, is recommended in patients 75 years of age or older.1(For dosage
recommendations in patients 75 years of age and older,see Geriatric Patients under Dosage and Administration:
Special Populations.) Aspirin (75-325 mg once daily) should be administered in conjunction
withenoxaparintherapy unless contraindicated.1When used with thrombolytic
1.2La mesure de l’activité anti-Xa devrait être envisagée pour les populations suivantes qui reçoivent une HFPM: obésité, insuffisance rénale, femme enceinte, pédiatrie (bébé < 2 mois), patient de faible poids (< 45 kg), patient âgé (> 80 ans) ou si on suspecte une surdose d’HFPM.
2.3 En traitement pour les patients obèses, envisager l’administration des HFPM aux doses usuelles en fonction du poids réel jusqu’à un poids maximal de 150 kg. Au-delà de 150 kg, limiter la dose au poids maximal de 150 kg et effectuer un suivi d’anti-Xa. L’évaluation du risque hémorragique ou embolique de chaque patient devra aussi être prise en considération afin d’individualiser le traitement.
2.4 En traitement pour les patients obèses, on peut envisager un suivi de l’activité anti-Xa au pic dans les cas suivants, uniquement lorsque le résultat risque d’influencer le devenir du patient: 2.4.1 Précocement (jour 2) si le poids est > 150 kg; 2.4.2 À long terme (> 7-10 jours) pour évaluer la bioaccumulation si le poids est >
100 kg.
GPC MONOGRAPHIES APES
AHA 2013 (QM) ESC 2012 (QM) AUS (QM) MONOGRAPHIE CANADIENNE MONOGRAPHIE ÉTATS-UNIENNE Guide de l’usage optimal des HFPM pour les patients obèses et insuffisants rénaux
● If age ≥75 y: no
● Regardless of age, if CrCl <30 Initial dosing of antithrombotic agents in patients with chronic
doses are given once every 24 h.
UFH is required. adaptation posologique n’est requise dans les autres indications chez les patients âgés, sauf en cas d’insuffisance rénale.
Emploi chez les insuffisants rénaux Le traitement de tous les patients insuffisants rénaux par des HBPM doit faire l’objet d’une surveillance étroite. L'exposition à l’énoxaparine augmente avec la gravité de l’insuffisance rénale. Chez les insuffisants rénaux, l’exposition accrue à l’énoxaparine s’accompagne d’un plus grand risque hémorragique (voir la section MODE D’ACTION ET PHARMACOLOGIE CLINIQUE, Populations particulières, Insuffisance rénale). On doit adapter la dose chez les patients atteints d’une insuffisance rénale grave (clairance de la créatinine < 30 mL/min), puisque l’exposition est augmentée de façon notable chez cette population de patients. Voici les recommandations
posologiques pour la prophylaxie et le traitement des patients atteints d’insuffisance rénale grave :
• Pour le traitement de l’infarctus aigu du myocarde avec sus-décalage du segment ST, la posologie recommandée est de 1 bolus i.v. de 30 mg, suivi immédiatement d’une dose de 1 mg/kg par voie s.-c., puis d’une dose de 1 mg/kg par voie s.-c. 1 fois par jour (maximum de 100 mg dans le cas de la première dose s.-c. seulement).
• Pour le traitement de l’infarctus aigu du myocarde avec sus-décalage du segment ST chez les patients âgés de ≥ 75 ans, la posologie recommandée est de 1 mg/kg par voie s.-c., 1 fois par jour (sans bolus initial) (maximum de 100 mg dans le cas de la première dose s.-c. seulement).
Administration IV
LOVENOX doit être administré au moyen d’un cathéter intraveineux. On ne doit pas mélanger ni employer LOVENOX avec d’autres médicaments. Pour éviter tout mélange éventuel de LOVENOX avec d’autres médicaments, la ligne d’injection choisie doit être rincée abondamment avec une solution saline ou de dextrose avant et après l’injection i.v. du bolus d’énoxaparine. LOVENOX peut être administré en toute sûreté dans une solution saline isotonique (0,9 %) ou dans une solution aqueuse de dextrose à 5 %.
initiated between 15 minutes before and 30 minutes after the start of thrombolytic therapy.1The optimal duration ofenoxaparintreatment is not known, but is likely to be more than 8 days since therapy was continued for 8 days or until hospital discharge in clinical trials.
For the treatment of acute ST-segment elevation MI in patients with severe renal impairment (creatinine clearance less than 30 mL/minute) who are younger than 75 years of age, the recommended initial dose of enoxaparin sodium is 30 mg as a single direct IV dose plus a 1-mg/kg subcutaneous dose; treatment should continue with a dosage of 1 mg/kg once daily (maximum of 100 mg per dose for each of the first 2 subcutaneous doses) given by subcutaneous injection with
concurrent aspirin therapy (75-325 mg daily).
For the treatment of acute ST-segment elevation MI in patients with severe renal impairment (creatinine clearance less than 30 mL/minute) who are 75 years of age or older, the
recommended initial dose of enoxaparin sodium is 1 mg/kg once daily (maximum of 75 mg per dose for each of the first 2 doses) given by subcutaneous injection with
concurrent aspirin therapy (75-325 mg daily); no initial IV dose should be given.
et 30 ml/min et que le risque hémorragique n’est pas élevé, les conduites suivantes peuvent être envisagées:
3.7.1 Énoxaparine (traitement; ClCr 20-30 ml/
min):
3.7.1.1 Monographie: dose ajustée à 1 mg/kg SC ID dans toutes les indications pour les patients avec une ClCr ≤ 30 ml/min;
3.7.1.2 Comité d’anticoagulothérapie:
3.7.1.2.1 SCA: 1 mg/kg SC ID;
3.7.1.2.1.1 Pas de suivi de l’activité anti-Xa si le traitement est de courte durée (≤ 7 jours) Dans le cadre du traitement d’un SCA, la dose d’énoxaparine de 1 mg/kg SC ID pourrait quant à elle être utilisée, puisqu’elle a été étudiée dans ce contexte clinique. D’ailleurs, la plupart des données disponibles proviennent de cette population et démontrent que cette dose semble sans danger et efficace pour les patients présentant une ClCr < 30 ml/min.
5.7. Anticoagulant : fondaparinux
GPC MONOGRAPHIE DOCUMENT CANADIEN
AHA 2013 (QM) ESC 2012 (QM) MONOGRAPHIE CANADIENNE SCC 2009
Fondaparinux administered with initial intravenous dose, followed in 24 hours by daily subcutaneous injections if the estimated creatinine clearance is greater than 30 mL/min, for the duration of the index hospitalization, up to 8 days or until revascularization.(Level of Evidence: B)
Fondaparinux is contreindicated if CrCl < 30 mL/min (Level of Evidence: B)
● Initial dose 2.5 mg IV, then 2.5 mg
subcutaneously daily starting the following day, for the index hospitalization up to 8 d or until revascularization
● Contraindicated if CrCl <30 mL/min Fondaparinux should not be given as the sole anticoagulant to patients referred for PCI and is contraindicated for patients with a creatinine clearance <30 mL/min.
Fondaparinux 2.5 mg i.v. bolus followed by a s.c. dose of 2.5 mg once daily up to 8 days or hospital discharge.
In patients treated with streptokinase, fondaparinux i.v.
bolus followed by s.c. dose 24 h later. IIa B
Initial dosing of antithrombotic agents in patients with chronic kidney disease (estimated creatinine clearance <60 mL/min):
Fondaparinux : No dose adjustment.
No experience in patients with end-stage renal disease or dialysis patients.
Finally, fondaparinux was shown in the large OASIS-6 trial to be superior
Finally, fondaparinux was shown in the large OASIS-6 trial to be superior