Ischaemic Heart Disease

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Ischaemic Heart Disease

• Clinical Pharmacology Seminar
• Phases 1 3
• James Rudd
• Cardiology SpR

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Ischaemic Heart Disease

• Angina
• Stable
• Unstable
• Prinzmetals
• Myocardial Infarction
• NSTEMI
• STEMI

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Angina

• Clinical syndrome exertional central chest
  tightness radiating to arms neck
• Oxygen demand exceeds supply
• Factors contributing
• HR, preload(venous return), afterload, aortic
  impedance all determine myocardial O2 requirements

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Management of stable angina

• Relieved/prevented by
• Slowing HR
• Reducing preload (impacts on LV wall stress thru
  LVEDP)
• Reducing afterload - BP
• Dilating coronary arteries
• Reducing myocardial contractility
• Also-
• Correct anaemia, tachyarrhythmias
• Modify CV risk factors Hypertension, DM,
  smoking cessation, Wt loss, graded exercise
• Prophylaxis before exercise

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Nitrates

• Reduce preload by venodilation, dilates
  coronaries, reduces afterload by systemic
  vasodilatation
• Different modes of delivery Spray, buccal, long
  acting, short acting, IV, patch
• Tachyphylaxis
• Lethal interaction with PDE5 inhibitors profound
  hypotension
• Adverse effects
• Headache
• Drug free period to prevent tolerance
  LA preps - 12 hours free
• Indications
• Angina, treatment of LVF

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ß blockers

• Reduce HR and contractility
• Less cardiac demand for O2
• Myocardium has ß1 2 receptors, coronary and
  peripheral arteries ß2 (sm. muscle dilation).
  Theoretic benefit for cardioselective agents
  but no significant differences. Nebivolol may
  have additional NO effects.
• Adv Effects
• Worsen/ precipitate heart blocks
• Lethargy
• Worsening acute cardiac failure but
  used in chronic stable heart failure
• Worsening COPD/asthma
• Worsening peripheral vascular disease
• Reduced mood / dreams CNS
  penetrating drugs
• Indications Primary prophylaxis of angina,
  secondary prevention (post MI ISIS 1 trial
  where reduction in deaths due to EMD). Not those
  with ISA, arrhythmias, HOCM, thyrotoxicosis,hypert
  ension, stable mod to severe heart failure,
  phaeochromocytoma, migraine prophylaxis

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Calcium channel blockers

• 2 main types
• Dihydropyridines Nifedipine, Amlodipine,
  Lercanidipine
• Reduce afterload by arteriolar dilation,
  dilate coronaries
• Non-dihydropyridines Diltiazem, Verapamil
• As above negative chronotropy by acting on
  SA AV nodes.
• Most are negative inotropes (non DH gtgt DH) except
  Amlodipine which is
• definitely safe in LV impairment
• Adverse effects
• Flushing, dizziness esp instant
  release preparations of Nifedipine
• Tachycardia (esp short acting preps -
  reflex tachycardia)
• Ankle oedema not heart failure. No
  indication for diuretics
• Non-DH SOB, heart block (esp with
  concomitant ß-blockers)
• Indications Angina, hypertension, post SAH,
  Raynauds
• Useful in vasospastic angina

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Potassium channel activators

• Vasodilatory properties (arterial and venous)
• Similar to other agents may have additional
  benefits as an adjunct (ie 3rd or 4th line)
• Nicorandil has a nitrate component
• Adv effects Headache esp on initiation
• Indications Angina
• IONA study When added to standard medications,
  nicorandil reduced death, NFMI by 17

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If channel inhibitor

• New anti-anginal - Ivabradine
• Blocks If (ionic funny channel) an mixed Na-K
  inward current activated by hyperpolarization and
  autonomic nervous system - lowers pacemaker
  activity in the SA-node
• Slows heart rate different mechanism from
  beta-blockers
• Adverse effects Luminous phenomena (retinal Ih
  channels similar to If channels) self-limiting
• Indications Angina
• Restricted use

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Management Strategy for Stable Angina

• 1.ASA
• 2.Lipid lowering agent
• 3. S/L GTN
• 4. ß-blocker or CCB which controls rate eg non-DH
• 5. Add CCB to ß-blocker or nitrate to CCB
• 6. CCB ß-blocker(DH) nitrate
• 7.Nicorandil
• 8. Coronary intervention PCI or CABG

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Acute Coronary Syndromes
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Acute Inferior MI
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Acute coronary syndromes - management

• Bed rest
• Oxygen
• Low molecular weight heparin
• Aspirin
• Clopidogrel
• IV nitrate
• Optimise oral therapy
• Stratify risk - ETT, stress imaging
  angiography
• Consider
• Tirofiban
• Intervention if pain fails to settle

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Myocardial Infarction- management

• Bed rest
• Oxygen
• ASA 300mg od stat
• Analgesia Diamorphine 2.5 5 mg IV (if no
  asthma/COPD) antiemetic Metoclopramide 10mg IV
• Thrombolysis SK, tPA
• If typical pain within 12 hours of
  presentation at any age
• New ST elevation or LBBB
• Adv effects haemorrhage, hypotension,
  bradycardia, reperfusion arrythmias, anaphylaxis

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Myocardial Infarction

• SK first choice, tPA for patients lt 60 within
  first 6 hours and anterior changes, cardiogenic
  shock, prev anaphylaxis with SK
• IV heparin to follow tPA
• Contraindications to thrombolysis
• Within 28 days of bleed, trauma,traumatic
  resuscitation
• Uncontrolled hypertension SBP gt 200, DBP gt
  120 mmHg - Rx IV GTN
• Aortic dissection
• Coma
• Known / suspected active peptic ulcer
  disease
• Recent CVA
• Defective haemostasis (warfarin per se is
  OK, unless INR very high - consult seniors)
• Severe renal/liver disease
• Acute pancreatitis
• Pregnancy / lactation
• Within 3 months of vascular surgery

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Antithrombogens

• Aspirin inhibits cyclo-oxygenase, prevents
  syntheses of TxA2 (pro-thrombotic)
• Thienopyridines (clopidogrel, ticlopidine)
  irreversibly inhibit binding of ADP during
  platelet activation. Used with Aspirin with drug
  eluting stents in NSTEMI. Expensive!!
• Glycoprotein 2b3a antagonists potent inhibitors
  of platelet aggregation eg. abciximab,
  eptifibatide, tirofiban

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IV ß-blockade - indications

• Indication as for thrombolysis
• Atenolol 5-10mg IV slow
• Contraindications Pulse lt 50, SBP lt100 mmHg,
  Asthma/COPD, conduction defects/sick sinus,
  uncontrolled CCF, severe PVD, poor LV function

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Secondary prophylaxis for IHD

• Aspirin to all patients
• ß-blocker to all patients
• ACE inhibition meta-analyses of SAVE, AIRE,
  TRACE in patients with LV dysfunction, HOPE in
  patients without LV dysfunction
• Lipid lowering for all patients
• Aggressive risk factor management hypertension,
  DM ,smoking cessation, cardiac rehabilitation

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EBM - MI

• ISIS (International Study of Infarct Survival) 1
  Atenolol reduces early mortality post MI
  (mainly due to reduction in EMD)
• ISIS 2 SK and ASA reduces 5 week mortality in
  patients with AMI
• ISIS 3 SK rtPA but rtPA associated with more
  cerebral bleeds
• ISIS 4 Captopril has a small but significant
  reduction in mortality post MI. IV Mg and
  nitrates no benefit

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EBM

• IHD
• CURE (Clopidogrel in Unstable Angina to prevent
  recurrent events) In ACS, clopidogrel ASA
  significantly reduces death from CV, non-fatal MI
  stroke compared to ASA alone
• HOPE (Heart Outcome Prevention Evaluation Study)
  Ramipril reduced MI, stroke, CV death in high
  risk patients
• Lipids
• 4S (Scand Simvastatin Survival Study)
  Simvastatin reduces risk of all major coronary
  events (relative risk reduction of 35) in
  patients with CAD mild-mod hypercholesterolemia
  (2º prevention)
• WOSCOPS (West of Scotland Coronary Prevention
  Study) Pravastatin reduced deaths from CHD, all
  cardiovascular causes and nonfatal MI in patients
  with hypercholesterolemia and no previous IHD (1
  º prevention)