Drug treatment of ACS : Angina

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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

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

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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

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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

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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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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
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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
Acute Coronary Syndromes
High Risk Minor Myoc damage
ST Elevation
Low-Risk
Non-ST Elevation
Troponin
Cardiac Markers
mortality
CK
ECG - Normal ST Depr/Transient
elevation ST elevation No Q Wave Q or
no Q
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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 (lt0.4) 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 HRlt60
  or BP lt90-heart block on transfer-STOP BETABLOCKER

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For Percutaneous, transluminal coronary,angioplast
y 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
• INRgt2-3, 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 gt 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