Judith Coombes 1

Drug treatment of ACS : Angina & Myocardial infarctionJudith 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

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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)

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Causes of Death 1996of all ages

0

5000

10000

15000

20000

25000

30000

35000

CHD CVA Lung Ca Breast Ca RTA AIDS

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Unstable Angina myocardial Infarction

Low-Risk High Risk‘Minor Myoc’

damage

Non-STElevation

ST Elevation

Car

diac

Mar

kers

mor

tali

ty

CK

Troponin

ECG - Normal ST Depr’/Transient elevation ST elevation

Acute Coronary Syndromes

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Principal Goals of TherapyCorrect 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

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Acute TreatmentMrs UA with chest pain at the officeOn 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 aggregationAt emergency Morphine and antiemetic Oxygen IV GTN Heparin

MONA

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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)

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TXA2

ADPGp IIb IIIaFibrinogen Receptor

Clopidogrel

CollagenThrombinTXA2

Activation

Aspirin

COX

ADP

Phosphodiesterase

Dipyridamole

Abciximab, tirofiban

Adaptaed from Schafer Al Am J Med 1996

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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

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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

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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

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Unstable Angina myocardial Infarction

Low-Risk High Risk‘Minor Myoc’

damage

Non-STElevation

ST Elevation

Car

diac

Mar

kers

mor

tali

ty

CK

Troponin

ECG - Normal ST Depr’/Transient elevation ST elevation

No Q Wave Q or no Q

Acute Coronary Syndromes

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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

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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

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Enzymes

DATE 26/3

0450

26/3

0650

26/3

2010

27/3

LDH 199 242 1400 1110

CK (20-200)

155 4130 5140

Tropinin

(<0.4)nd 2.79 2.22

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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

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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

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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

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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)

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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

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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

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Lysis

Streptokinase Urokinase (not in AUS) Alteplase (tPA) Reteplase (r-PA) Tenecteplase (TNK t-PA)

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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

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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

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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

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Cautions

Hypotension, bradycardia, asthma Relative contra-indications:

? Asthmatic Heart failure Diabetics PVD

Awareness, lethargy, hypotension, cold peripheries, impotence

Ineffective dosing !

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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

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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

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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

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Remember

Secondary prevention Aspirin Betablocker ACE inhibitor Lipid Reduction

EDUCATION-Cardiac rehabilitation