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Drug treatment of ACS : Angina & Myocardial infarction Judith Coombes Conjoint Senior Lecturer, University of Queensland Senior Pharmacist, Education, Princess Alexandra Hospital Judith Coombes 1 Objectives STEMI and NSTEACS Acute treatment of unstable angina Mechanism and evidence Acute treatment of Myocardial infarction Mechanism and evidence Judith Coombes 2 Evidence ACS has a huge number of large multicentre trails providing evidence for treatment choices. Trial results make ACS fairly protocol driven www.NICE.org.uk www.clinicalevidence.con Cochrane data base Guidelines for the management of acute coronary syndromes 2006 (National Heart Foundation) Judith Coombes 3 Causes of Death 1996 of all ages 35000 30000 25000 20000 15000 10000 5000 0 CHD CVA Lung Ca Judith Coombes Breast Ca RTA AIDS 4 Judith Coombes 5 Acute Coronary Syndromes Unstable Angina Cardiac Markers Low-Risk myocardial Infarction High Risk ‘Minor Myoc’ damage Non-ST Elevation ST Elevation CK ECG - Normal elevation ST Depr’/Transient elevation Judith Coombes mortality Troponin ST 6 Principal Goals of Therapy Correct O2 demand vs supply imbalance reduce pre-load on the heart (amount of blood returning to be pumped out) improve coronary artery circulation reduce ionotropic (force) and chronotropic (rate) activity of myocardium - O2 demand Stop formation of fibrin clot and progression of thrombus Prevent myocardial infarction Judith Coombes 8 Acute Treatment Mrs UA with chest pain at the office On route to hospital s/l GTN - coronary dilation & off load heart 1-3 tablet/ sprays every 5 mins then 000 3 month expiry on tablets, keep in glass Aspirin 300mg - inhibit platelet aggregation At emergency Morphine and antiemetic Oxygen IV GTN Heparin MONA Judith Coombes 9 Heparin Use in UA Enoxaparin superior to UH heparin in reducing death and MI-in trials Role for Acute of IV heparin whilst assessing need for intervention (angioplasty & stent) Judith Coombes 10 Clopidogrel Dipyridamole ADP Gp IIb IIIa Fibrinogen Receptor ADP COX Abciximab, tirofiban TXA2 Phosphodiesterase Activation Collagen Thrombin TXA2 Aspirin Adaptaed from Schafer Al Am J Med 1996 Judith Coombes 11 Aspirin Antiplatelet activity Decrease 35 day Mortality by 23% Halved incidence re-infarction + stroke In addition to thrombolysis decrease mortality by 50% Saves 30 lives/ 1000 patients Benefits sustained at 10 years Judith Coombes 12 Glycoprotein IIb/IIIa antagonists Platelets central to coronary thrombosis G2b3a antagonists block platelets binding together eg ABCIXIMAB (Reoppro) Tirofiban (Aggrostat) in combination with Aspirin & UH reduced combined end points Death, MI angina Use in High risk patients prior to angiography Judith Coombes 13 Clopidogrel (Iscover, Plavix) Act as inhibitor of platelet aggregation 75mg daily Used 4 weeks only with aspirin post angioplasty and stent Suitable alternative to aspirin Additive benefit to aspirin Increased bleeding time Judith Coombes 14 Judith Coombes 15 Acute Coronary Syndromes Cardiac Markers Low-Risk ECG - Normal myocardial Infarction High Risk ‘Minor Myoc’ damage Non-ST Elevation ST Elevation Troponin CK ST Depr’/Transient elevation No Q Wave Judith Coombes mortality Unstable Angina ST elevation Q or no Q 16 Myocardial Infarction Plaque rupture Involving total occlusion of one or more coronary arteries Significant myocardial muscle damage (necrosis) Risks of death, further MIs, heart failure, arrhythmia, CVA Judith Coombes 17 Mr MI dob 1957 Ambulance gave Aspirin and GTN +pain relief Somewhere he fell ? GTN ? Laceration over eyebrow dressed Emergency of another hospital Acute inferior MI, ST elevation (STEMI) 3mm ST elevation on ECG Enzymes Judith Coombes 18 Enzymes DATE 26/3 0450 26/3 0650 26/3 2010 27/3 LDH 199 242 1400 1110 CK 155 4130 5140 nd 2.79 (20-200) Tropinin (<0.4) 2.22 Judith Coombes 19 Continued in emergency Morphine 2.5mg IV heparin IV GTN TNK tPA (tenecteplase iv)-resolution of ST elevation, further ST elevation 3 hrs later-so transfer IV Metoprolol 2.5-5mg every 10 mins until HR<60 or BP <90-heart block on transferSTOP BETABLOCKER Judith Coombes 20 For Percutaneous, transluminal coronary,angioplasty PTCA Clopidogrel 300mg as pre med then 75mg daily for 1 month- 6 months- 12 months or longer for drug eluting stents Judith Coombes 21 Regular Medications Aspirin 100mg mane Clopidogrel 75mg mane Atorvastatin 40mg nocte Captopril 25mg tds Start metoprolol (12.5mg bd) at low dose the next day Judith Coombes 22 Myocardial Infarction-What has to be prevented ? Prevent secondary problems Significant risk of Death myocardial necrosis Arrhythmias Unstable angina Re-infarction LVF TIME IS MUSCLE (was door to needle time now more like pain to reperfusion time) Judith Coombes 23 Acute Treatment 50% MI deaths - pre-hospital Mortality at 1 month approx 10% in hospital Nitrates s/l or Iv Aspirin PCI/Thrombolysis or angioplasty-to reopen the vessel streptokinase, alteplase, retaplase (rtPA), tenecteplase Judith Coombes 24 Aspirin Antiplatelet activity Decrease 35 day Mortality by 23% Halved incidence re-infarction + stroke In addition to thrombolysis decrease mortality by 50% Saves 30 lives/ 1000 patients Benefits sustained at 10 years Judith Coombes 25 Lysis Streptokinase Urokinase (not in AUS) Alteplase (tPA) Reteplase (r-PA) Tenecteplase (TNK t-PA) Judith Coombes 26 Tissue Plasminogen activator Plasmin is a proteolytic enzyme which cleaves fibrin plasmin is active form of plasminogen activated by tissue plasminogen activator when fibrin is formed plasminogen and tpa are specifically absorbed onto fibrin Judith Coombes 27 Contraindications Absolute Risk of bleeding Risk of intracranial bleed Active internal, nuerosurgery in last 6 months, intracranial bleed Haemorrhagic stroke-ever, stroke in past year, cerebral neoplasm Suspected aortic dissection Relative INR>2-3, traumatic CPR, trauma, major surgery in past month, internal bleeding past 2-3 weeks, peptic ulcer, previous stroke or TIA Judith Coombes 28 Beta-Blockers -ve ionotrope & chronotrope, anti-arrhythmic Metoprolol and atenolol - not a class effect Must use a dose to properly “beta-block” Long term saves 35-60 lives/ 1000 at 3years Prevents 60 infarcts/ 1000 at 3 years. Prevents angina, arrhythmias, sudden death Judith Coombes 29 Cautions Hypotension, bradycardia, asthma Relative contra-indications: ? Asthmatic Heart failure Diabetics PVD Awareness, lethargy, hypotension, cold peripheries, impotence Ineffective dosing ! Judith Coombes 30 ACE-Inhibitors Captopril (Capoten,Acenorm), lisinopril (Zestril,Prinvil), Ramipril (Tritace), Perindopril (Coversyl) - Class effect Treat & prevent left ventricular failure 3-30 lives saved/ 1000 patients Some patients short term (6/52) only Start early and aim for highest doses Captopril - 50mg TDS, Lisinopril 20mg D, Ramipril 10mg D Judith Coombes 31 Cautions Need baseline blood pressure and creatinine Hypotension some concern on first dose Impaired renal function not contra indication worse if dehydrated and on other vasodilators Renal artery stenosis Rapidly worsening renal function Cough - ? swap drug No post MI evidence for AGII Receptor antag Judith Coombes 32 Dyslipidaemia- more chronic than acute 35-50% of MI patients have cholesterol > 5.5 mmol/l Statins significantly decrease mortality and re-infarction Pravastatin, simvastatin, atorvostatin Judith Coombes 33 Remember Secondary prevention Aspirin Betablocker ACE inhibitor Lipid Reduction EDUCATION-Cardiac rehabilitation Judith Coombes 34