Drug treatment of ACS : Angina & Myocardial infarction

1. Drug treatment of ACS :Angina&Myocardial infarction Judith Coombes Conjoint Senior Lecturer, University of Queensland Senior Pharmacist, Education, Princess Alexandra Hospital Judith Coombes

2. Objectives STEMI and NSTEACS • Acute treatment of unstable angina • Mechanism and evidence • Acute treatment of Myocardial infarction • Mechanism and evidence Judith Coombes

3. 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

4. Causes of Death 1996of all ages Judith Coombes

5. Judith Coombes

6. Acute Coronary Syndromes Unstable Angina myocardial Infarction High Risk ‘Minor Myoc’ damage ST Elevation Low-Risk Non-ST Elevation Troponin mortality Cardiac Markers CK ECG - Normal ST Depr’/Transient elevation ST elevation Judith Coombes

7. 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. Mechanisms of action of antiplatelet agents Clopidogrel Dipyridamole ADP Phosphodiesterase Gp IIb IIIa Fibrinogen Receptor ADP Activation COX Abciximab, tirofiban TXA2 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 Unstable Angina myocardial Infarction High Risk ‘Minor Myoc’ damage ST Elevation Low-Risk Non-ST Elevation Troponin mortality Cardiac Markers CK ECG - Normal ST Depr’/Transient elevation ST elevation No Q Wave Q or no Q Judith Coombes

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 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 transfer-STOP 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 LVF • Arrhythmias • Unstable angina • Re-infarction 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 • Active internal, nuerosurgery in last 6 months, intracranial bleed • Risk of 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 • Impaired renal function not contra indication • Hypotension some concern on first dose- • 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