Antithrombotic Therapy in ACS Pretreatment in STEMI Christian W. Hamm Kerckhoff Heart & Thorax Center Bad Nauheim Germany
Potential conflicts of interest Speaker s name: Christian W. Hamm I have the following potential conflicts of interest to report: Research contracts: Consulting: GSK, The Medicines Comp., MSD, Braun, Siemens, Cordis, AstraZeneca, BRAHMS, Pfizer, Lilly GSK, Pfizer, MSD, Cordis, Medtronic, Lilly, BMS, CVT, SanofiAventis, Iroko, Abbott, Roche, BRAHMS, AstraZeneca, Daiichi Sankyo, The Medicines Comp., Braun, Boehringer Ingelheim
STEMI Network Symptoms compatible with STEMI Pre-hospital diagnosis, triage, care EMS GP/cardiologist Self-decision Ambulance Private transportation PCI-capable hospital Transfer Non-PCI-capable hospital ESC Guidelines STEMI 2008
ACS with ST Elevation Invasive strategy preferred Skilled PCI lab available < 90 minutes High Risk from STEMI Cardiogenic shock, Killip class 3 Contraindications to fibrinolysis increased risk of bleeding / ICH Late presentation > 3 hours from symptom onset Diagnosis of STEMI is in doubt
Primary PCI vs. thrombolytic therapy Transfer for primary PCI Dalby. Circulation 2003;108:1809
Primary therapeutic measures Oxygen Insufflation (4 to 8 L/min) if oxygen saturation is < 90% Nitrates Sublingually or intravenously (caution if systolic blood pressure < 90mmHg) Aspirin Clopidogrel Initial dose of 160 325mg non-enteric formulation followed by 75 100 mg/d (intravenous administration is acceptable) Loading dose of 300mg (or 600mg for rapid onset of action) followed by 75 mg daily Anticoagulation Choice between differrent options depends on strategy: UFH intravenous Bolus 60 70 IU/kg (maximum 5000 IU) followed by infusion of 12 15 IU/kg/h (IU/h maximum 1000) titrated to aptt 1.5 2.5 times control Fondaparinux 2.5 mg/daily subcutaneously Enoxaparin 1 mg/kg twice/daily subcutaneously Dalteparin 120 IU/kg twice/daily subcutaneously Nadroparin 86 IU/kg twice/daily subcutaneously Bivalirudin 0.1 mg/kg bolus followed by 0.25 mg/kg/h Morphine Oral betablocker 3 to 5 mg intravenous or subcutaneous, depending on pain severity Particularly, if tachycardia or hypertension without sign of heart failure Atropine 0.5-1 mg intravenously, if bradycardia or vagal reaction ESC Guidelines for the Management of NSTE-ACS
1 st to 2 nd Door Medical Treatment ASS? Clopidogrel Heparin Nitroglycerin Analgetic Glycoprotein IIb/ IIIa?
Clinical Events until Day 7 or hospital discharge % 8 7 Prehospital Standard 7 n = 337 6 5 5,2 4 3 2 1 2,3 0,6 0,6 1,7 2,5 3 1,2 0,6 0 Death Reinfarction Re-PCI Death/MI/Re-PCI CABG U. Zeymer et al, 2010
Adjusted risk of death Swedish Coronary Angiography and Angioplasty Registry (SCAAR) 0.06 0.04 0.03 No upstream clopidogrel upstream clopidogrel Primary PCI 0.02 0.01 Hazard ratio 0.76 (95% CI = 0.59-0.98) N = 13.847 0.00 0 5 10 15 20 25 30 Time (Day after PCI) S. Koul et al, ESC 2010
Oral P2Y 12 Inhibitors Clopidogrel Prasugrel Ticagrelor Drug class Thienopyridine Thienopyridine ATP analogue Reversibility irreversible irreversible reversible Route of administration oral oral oral Time to peak effect 2-3h 1 h 120-240 min Drug elimination half-life 3 h 3.7 h 12 h Duration of action 5-8 days 5-10 days 24 h Trials CURE CHARISMA TRITON PLATO
1 st to 2 nd Door Medical Treatment ASS? Clopidogrel Heparin Nitroglycerin Analgetic Glycoprotein IIb/ IIIa?
Facilitated PCI Meta-Analysis 21 Trials > 8000 Patients IIbIIIa inhibitors Lysis Combo Rx On-Time 1 &2 Assent-4 Advance-MI Tiger-PA Sami Brave Erami Prague Finesse Reomobile Limi Zorman Pact Cutlip Gracia-2 ReoPro-Bridging Intami Finesse Finesse Bellandi BRAVE 3 Keeley Lancet 2006;367:579
ACC 2009, Orlando Ongoing Tirofiban In Myocardial Infarction Evaluation All-Cause Mortality 1-Year P = 0.077 (n = 1398)
ON TIME 2: Prehospital Tirofiban Better ST resolution More aborted AMI v t Hof et al., Lancet 2008
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