Transcript Drug Treatment of Ischaemic Heart Disease

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
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Acute treatment of unstable angina
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Mechanism and evidence
Acute treatment of Myocardial infarction
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Mechanism and evidence
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Evidence
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ACS has a huge number of large multicentre
trails providing evidence for treatment
choices.
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Trial results make ACS fairly protocol driven
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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 1996
of all ages
35000
30000
25000
20000
15000
10000
5000
0
CHD
CVA
Lung Ca
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Breast Ca
RTA
AIDS
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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
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mortality
Troponin
ST
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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
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Prevent myocardial infarction
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Acute Treatment
Mrs UA with chest pain at the office
On route to hospital
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s/l GTN - coronary dilation & off load heart
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1-3 tablet/ sprays every 5 mins then 000
3 month expiry on tablets, keep in glass
Aspirin 300mg - inhibit platelet aggregation
At emergency
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Morphine and antiemetic
Oxygen
IV GTN
Heparin
MONA
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Heparin Use in UA
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Enoxaparin superior to UH heparin in
reducing death and MI-in trials
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Role for Acute of IV heparin whilst assessing
need for intervention (angioplasty & stent)
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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
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Aspirin
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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
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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)
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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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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
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mortality
Unstable Angina
ST elevation
Q or no Q 16
Myocardial Infarction
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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
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Ambulance gave Aspirin and GTN +pain
relief
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Somewhere he fell ? GTN ? Laceration over eyebrow
dressed
Emergency of another hospital
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Acute inferior MI, ST elevation (STEMI)
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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
155
4130
5140
nd
2.79
(20-200)
Tropinin
(<0.4)
2.22
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Continued in emergency
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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
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For Percutaneous, transluminal
coronary,angioplasty PTCA
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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
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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 ?
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Prevent secondary problems
Significant risk of
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Death
myocardial necrosis
Arrhythmias
Unstable angina
Re-infarction
LVF
TIME IS MUSCLE (was door to needle time
now more like pain to reperfusion time)
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Acute Treatment
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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
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streptokinase, alteplase, retaplase (rtPA),
tenecteplase
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Aspirin

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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
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Streptokinase
Urokinase (not in AUS)
Alteplase (tPA)
Reteplase (r-PA)
Tenecteplase (TNK t-PA)
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Tissue Plasminogen activator
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Plasmin is a proteolytic enzyme which
cleaves fibrin
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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
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Absolute
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Risk of bleeding
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Risk of intracranial bleed
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Active internal, nuerosurgery in last 6 months, intracranial bleed
Haemorrhagic stroke-ever, stroke in past year, cerebral neoplasm
Suspected aortic dissection
Relative
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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
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-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
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Hypotension, bradycardia, asthma
Relative contra-indications:
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? Asthmatic
Heart failure
Diabetics
PVD
Awareness, lethargy, hypotension, cold
peripheries, impotence
Ineffective dosing !
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ACE-Inhibitors
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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
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Need baseline blood pressure and creatinine
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Hypotension some concern on first dose
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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
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Dyslipidaemia- more chronic than
acute
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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
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Secondary prevention
Aspirin
Betablocker
ACE inhibitor
Lipid Reduction
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EDUCATION-Cardiac rehabilitation
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