Treatments For Acute And Chronic Ischaemic Heart Disease

4.9.06

Manifestations of ischaemic heart disease
• Sudden death.
• Angina pectoris (1% of entire population):
-stable;
-unstable.
• Myocardial infarction.
• Cardiac failure.

Stable angina - intermittent
• Mismatch of oxygen demand:
-exercise;
-increased ventricular wall tension.
• And supply:
-obstruction - fixed (atheroma), dynamic (spasm) or both;
-anaemia etc.;
-[aortic stenosis].

Treatment of acute attack in stable patient
• Rest.
• GTN - sublingually.
• If not responding quickly, seek help.
• Careful advice to patient about dealing with these episodes.

Chronic treatment of stable angina
• Deal with risk factors aggressively - smoking, hypercholesterolaemia, blood pressure etc.
-aspirin and statins.
• Drug treatment:
-nitrates;
-beta-blockers;
-calcium channel blockers;
-nicorandil.

Nitrates
• Cellular actions - via nitric oxide, nitrosothiols, activation of cGMP.
• Vasodilators:
-venous - decreased venous return, preload - decreased oxygen demand (major);
-arterial - decreased blood pressure, afterload and oxygen demand;
-coronary arteries - increased oxygen supply (minor usually, except in coronary artery spasm).

Adverse effects of nitrates
• Headache.
• Low blood pressure and tachycardia.
• Tolerance - depletion of -SH groups.

Examples and use
• GTN - sublingually (IV), first pass metabolism:
-acute attack/prophylaxis;
-congestive cardiac failure.
• Isosorbide mononitrate (ISMN):
-oral, prophylaxis, often modified release preparations.
• ISDN - oral and IV, angina and congestive cardiac failure.

Beta-blockers
• Block β-adrenoceptor:
-β1 v β2, selectively/nonselectively.
• Used in angina, hypertension.
• Slows the heart, especially during exercise:
-decreases oxygen demand;
-prolonged diastole (when coronary blood flow occurs);
-improves oxygen supply.

Uses of beta-blockers
• Angina.
• [Hypertension.]
• Cardiac arrhythmias.
• After myocardial infarction.
• Congestive cardiac failure.
• Anxiety.
• Thyrotoxicosis.

Examples
• Propanolol - nonselective, lipophilic - liver metabolism.
• Atenolol - selective, hydrophilic.
• [Carvedilol, bisoprolol in congestive cardiac failure.]

Adverse effects
• Bradycardia.
• Peripheral vasoconstriction.
• Bronchoconstriction.
• Rebound - "up regulation" - increased sensitivity to and amount of beta-receptors.
• Congestive cardiac failure.
• Fatigue, depression.

Calcium channel blockers
• Inhibit voltage-dependent calcium channel and decrease Ca2+ entry.
• Reduce smooth muscle contraction.
• Cause vasodilation:
-arterial;
-coronary;
-venous.
• Decreased force of contraction of heart.
• Used in angina and hypertension.

Examples
• Oral, prophylaxis.
• Three classes:
-bind to different, but related, receptor sites - different actions in different tissues;
-nifedipine (dihidropyridines) and relatives - vasodilation, angina, blood pressure;
-verapamil - supraventricular arrhythmias, angina, blood pressure;
-diltiazem - angina, blood pressure.

Adverse effects
• Nifedipine - headache, blood pressure decrease, heartburn, facial flushing, ankle swelling, dizziness.
• Verapamil - headache, dizziness, constipation, heart block, bradycardia.
• Diltiazem - constipation, ankle oedema, flushing, headache.
• All - congestive cardiac failure.
• Interactions - verapamil + beta-blockers - both slow heart, possibly to point of stoppage.

Nicorandil
• Potassium channel opener (mimics calcium channel blockers) and nitrate-like activity.
• Vasodilator.
• ?Other effects??
• Reserve drug for difficult cases.

Choosing a drug
• Aspirin, statins, GTN as required.
• Beta-blockers single best.
• If contraindicated or ineffective, ?calcium channel blocker, ?nitrate.
• Double/triple therapy common.

Invasive treatments
• High-risk patients.
• Patients not controlled with medication.
• Patient preference.
• For most part, no improvements in mortality, but improvement in symptoms.
• PTCA - percutaneous transluminal coronary angioplasty.
• PTCA with stent.
• CABG - coronary artery bypass grafting.

[ST elevation = "tombstone".]

Treatment for STEMI (ST elevation myocardial infarction)
• GTN sublingually.
• Aspirin.
• Pain relief - diamorphine + antiemetic.
• Thrombolysis (early angioplasty?)
-?followed by heparin.
• Antianginals if ongoing pain: beta-blockers and nitrates.

Thrombolysis
• All drugs activate thrombolysis by promoting formation of plasmin from plasminogen.
• Break down fibrin.
• "Golden hour."
• Up to 12 (?24) hours.
• Reduce mortality at 30 days from 12% to 9%.

Thrombolytic drugs
• Streptokinase - short infusion.
• Alteplase - infusion over 90 minutes + heparin.
• Tenecteplase - bolus +heparin.

Hazards
• Anaphylaxis/hypotension (streptokinase).
• Loss of effect, if antibodies.
• Bleeding - intracranial haemorrhage especially.
• Reperfusion arrhythmias.
• Contraindications:
-[prolonged CPR];
-history of bleeding, recent surgery;
-risk of bleeding.
• Excessive bleeding - antifibrinolytics - tranexamenic acid.

Treat complications
• Arrhythmias.
• Congestive cardiac failure.
• Others:
-physical;
-psychological - rehabilitation etc.