Ischaemic Heart Disease miocardial infarction

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					Ischaemic Heart Disease

 Clinical Pharmacology Seminar
           Phases 1 & 3

         James Rudd
        Cardiology SpR
            Ischaemic Heart Disease
 Angina

 Myocardial Infarction

 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
            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
 Reduce preload by venodilation, dilates coronaries, reduces afterload by systemic
 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
                                      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,hypertension, stable mod to severe heart failure, phaeochromocytoma, migraine
                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 >> 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, Raynaud’s
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            Potassium channel activators
 Vasodilatory properties (arterial and venous)
 Similar to other agents – may have additional benefits as an adjunct
  (ie 3 rd 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%
                   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
  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
           Acute Coronary Syndromes
              Stable Angina                    STEMI         NSTEMI

Character of
             Exertional pain     Rest pain     Rest pain     Rest pain

               Responds to
 Relievers        GTN
                               No GTN effect No GTN effect No GTN effect

 Enzymes          Normal          Normal       Elevated       Elevated

                                 Often ST     ST segment   No ST segment
   ECG         Often normal
                                depression     elevation     elevation
Acute Inferior MI
    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
               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
                  Myocardial Infarction
 SK first choice, tPA for patients < 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 > 200, DBP > 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
 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.

 Glycoprotein 2b3a antagonists – potent inhibitors of
  platelet aggregation eg. abciximab, eptifibatide, tirofiban
          IV ß-blockade - indications
 Indication as for thrombolysis
 Atenolol 5-10mg IV slow
 Contraindications: Pulse < 50, SBP <100 mmHg,
  Asthma/COPD, conduction defects/sick sinus,
  uncontrolled CCF, severe PVD, poor LV function
       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
                       EBM - MI

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