1. Judith Coombes1 Drug treatment of ACS : Angina & Myocardial infarction Judith Coombes Conjoint Senior Lecturer, University of Queensland Senior Pharmacist, Education, Princess Alexandra Hospital

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

3. 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)

4. Judith Coombes 4 Causes of Death 1996 of all ages

5. Judith Coombes 5

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

7. Judith Coombes 7 Unstable Angina Due to rupture of arthersclerotic plaque - increased platelet aggregation (platelet thrombi), vasospasm and formation of clot. Not a total occlusion of blood vessel May be associated with some muscle damage  Recent onset- pain at rest  Crescendo  Angina occurring post MI

8. Judith Coombes 8 Principal Goals of Therapy Correct O 2 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 - O 2 demand Stop formation of fibrin clot and progression of thrombus  Prevent myocardial infarction

9. Judith Coombes 9 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

10. Judith Coombes 10 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)

11. Judith Coombes 11 TXA2 ADP Gp IIb IIIa Fibrinogen Receptor Clopidogrel Collagen Thrombin TXA2 Activation Aspirin COX ADP Phosphodiesterase Dipyridamole Abciximab, tirofiban Adaptaed from Schafer Al Am J Med 1996

12. Judith Coombes 12 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

13. Judith Coombes 13 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

14. Judith Coombes 14 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

15. Judith Coombes 15

16. Judith Coombes 16 Unstable Angina myocardial Infarction Low-Risk High Risk ‘Minor Myoc’ damage Non-ST Elevation ST Elevation Cardiac Markers mortality CK Troponin ECG - Normal ST Depr’/Transient elevationST elevation No Q WaveQ or no Q Acute Coronary Syndromes

17. Judith Coombes 17 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

18. Judith Coombes 18 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

19. Judith Coombes 19 Enzymes DATE26/3 0450 26/3 0650 26/3 2010 27/3 LDH19924214001110 CK (20-200) 15541305140 Tropinin (<0.4) nd2.792.22

20. Judith Coombes 20 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

21. Judith Coombes 21 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

22. Judith Coombes 22 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

23. Judith Coombes 23 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)

24. Judith Coombes 24 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

25. Judith Coombes 25 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

26. Judith Coombes 26 Lysis Streptokinase Urokinase (not in AUS) Alteplase (tPA) Reteplase (r-PA) Tenecteplase (TNK t-PA)

27. Judith Coombes 27 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

28. Judith Coombes 28 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

29. Judith Coombes 29 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

30. Judith Coombes 30 Cautions Hypotension, bradycardia, asthma Relative contra-indications:  ? Asthmatic  Heart failure  Diabetics  PVD Awareness, lethargy, hypotension, cold peripheries, impotence Ineffective dosing !

31. Judith Coombes 31 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

32. Judith Coombes 32 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

33. Judith Coombes 33 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

34. Judith Coombes 34 Remember Secondary prevention Aspirin Betablocker ACE inhibitor Lipid Reduction EDUCATION-Cardiac rehabilitation