Cardiac Pharmacology: Difference between revisions

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{{DevelopmentPhase}}
''Heather Melrose, Jonas de Jong''
''Heather Melrose, Jonas de Jong''


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==Renin-Angiotensin-Aldosterone System==
==Renin-Angiotensin-Aldosterone System==
[[Image:Renin-angiotensin-aldosterone_system.png|thumb|right|500px|RAAS schematic]]
The renin-angiotensin-aldosterone system (RAAS) is an important hormone-based pathway within the body that regulates fluid balance and thus systemic blood pressure. The system is activated by decreases in blood volume or pressure detected in two ways: a drop in blood pressure detected by baroreceptors (pressure sensors) located in the carotid sinus or a drop in flow rate through the kidneys, detected by the juxtaglomerular apparatus. The body responds to these stimuli to effect a restoration in blood pressure via the actions of three hormones; renin, angiotensin and aldosterone. Following the detected drop in blood pressure, the enzyme renin is released from specialised cells within the kidney. The substrate of renin is the inactive precursor of angiotensin I, angiotensinogen. Angiotensin I is then enzymatically converted by angiotensin converting enzyme (ACE) into angiotensin II, a hormone with various actions throughout the body that ultimately increase blood pressure, restoring fluid balance within the body.  
The renin-angiotensin-aldosterone system (RAAS) is an important hormone-based pathway within the body that regulates fluid balance and thus systemic blood pressure. The system is activated by decreases in blood volume or pressure detected in two ways: a drop in blood pressure detected by baroreceptors (pressure sensors) located in the carotid sinus or a drop in flow rate through the kidneys, detected by the juxtaglomerular apparatus. The body responds to these stimuli to effect a restoration in blood pressure via the actions of three hormones; renin, angiotensin and aldosterone. Following the detected drop in blood pressure, the enzyme renin is released from specialised cells within the kidney. The substrate of renin is the inactive precursor of angiotensin I, angiotensinogen. Angiotensin I is then enzymatically converted by angiotensin converting enzyme (ACE) into angiotensin II, a hormone with various actions throughout the body that ultimately increase blood pressure, restoring fluid balance within the body.  


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==Neural Control of the Cardiovascular System==
==Neural Control of the Cardiovascular System==
[[File:Sympathic_parasympathic.svg|thumb|400px|Interaction between the sympathic and parasympathic nervous system and the heart]]
===Sympathetic (Adrenergic) Nervous System===
===Sympathetic (Adrenergic) Nervous System===
The adrenergic nervous system is a vital component of many processes throughout the body, including the cardiovascular system. Circulating catecholamines (e.g. adrenaline and noradrenaline) bind to and activate adrenergic receptors on cell membranes. Adrenergic receptors are a class of G-protein coupled receptors that elicit a variety of tissue-specific effects and exist in several subtypes.  
The adrenergic nervous system is a vital component of many processes throughout the body, including the cardiovascular system. Circulating catecholamines (e.g. adrenaline and noradrenaline) bind to and activate adrenergic receptors on cell membranes. Adrenergic receptors are a class of G-protein coupled receptors that elicit a variety of tissue-specific effects and exist in several subtypes.  
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==Platelet/Clotting System==
==Platelet/Clotting System==
[[File:Platelet_receptors.svg|thumb|400px|Platelet activation and inhibition operates through surface receptors on platelets. Feedback loops enhance platelet activation (e.g. ADP released by platelets increases platelet activation, through the ADP receptor)]]
Platelets (also known as thrombocytes) are small cells lacking nuclei that are responsible for haemostasis, or blood clotting. Damage or injury leading to blood loss and exposure of extracellular collagen fibres is detected, activating platelets. Once activated, platelets become adhesive, sticking to both the damaged vessel wall and each other, forming a clump of cells, or ‘clot’, helping to dam the vessel leak. They then begin to secrete cytokines that encourage invasion of fibroblasts present in the surrounding tissue which form a more permanent patch, either by creating healthy tissue, or depositing extracellular matrix to form a scar.  
Platelets (also known as thrombocytes) are small cells lacking nuclei that are responsible for haemostasis, or blood clotting. Damage or injury leading to blood loss and exposure of extracellular collagen fibres is detected, activating platelets. Once activated, platelets become adhesive, sticking to both the damaged vessel wall and each other, forming a clump of cells, or ‘clot’, helping to dam the vessel leak. They then begin to secrete cytokines that encourage invasion of fibroblasts present in the surrounding tissue which form a more permanent patch, either by creating healthy tissue, or depositing extracellular matrix to form a scar.  


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|Hypertension: Class IA <cite>Esc2</cite>
|Hypertension: Class IA <cite>Esc2</cite>


Hypertension in symptomatic (NYHA class II-IV) HF and LVD: Class IA <cite>Esc3</cite>
Hypertension in symptomatic (NYHA class II-IV) HF and LVD: Class IA <cite>Esc1</cite>


Hypertension in diabetics: Class IA <cite>Esc4</cite>
Hypertension in diabetics: Class IA <cite>Esc3</cite>
|rowspan="4" valign="top"|Hypotension (2.4%), renal impairment, persistent dry cough, angioedema, rash pancreatitis, upper respiratory-tract symptoms (2-10%), gastro-intestinal symptoms (1-2%), altered liver function tests, cholestatic jaundice, hepatitis, fulminant hepatic necrosis and failure, hyperkalaemia (2%), hypoglycaemia, blood disorders including thrombocytopenia, leucopenia, neutropenia, headache (3%), dizziness (2-12%), fatigue, malaise, taste disturbance, paraesthesia, bronchospasm, fever, serositis, vasculitis, myalgia (3%), arthralgia, positive antinuclear antibody, raised erythrocyte sedimentation rate, eosinophilia, leucocytosis, and photosensitivity.
|rowspan="4" valign="top"|Hypotension (2.4%), renal impairment, persistent dry cough, angioedema, rash pancreatitis, upper respiratory-tract symptoms (2-10%), gastro-intestinal symptoms (1-2%), altered liver function tests, cholestatic jaundice, hepatitis, fulminant hepatic necrosis and failure, hyperkalaemia (2%), hypoglycaemia, blood disorders including thrombocytopenia, leucopenia, neutropenia, headache (3%), dizziness (2-12%), fatigue, malaise, taste disturbance, paraesthesia, bronchospasm, fever, serositis, vasculitis, myalgia (3%), arthralgia, positive antinuclear antibody, raised erythrocyte sedimentation rate, eosinophilia, leucocytosis, and photosensitivity.
|-
|-
|Heart Failure
|Heart Failure
|Captopril: 12.5mg 3 times daily
|Captopril: 12.5mg 3 times daily
|Post STEMI: Class IA <cite>Esc5</cite>
|Post STEMI: Class IA <cite>Esc4</cite>


Diabetic patients: Class IC <cite>Esc6</cite>
Diabetic patients: Class IC <cite>Esc2</cite>


Symptomatic (NYHA class II-IV) HF: Class IA; Acute heart failure with ACS: Class IA <cite>Esc7</cite>
Symptomatic (NYHA class II-IV) HF: Class IA; Acute heart failure with ACS: Class IA <cite>Esc1</cite>
|-
|-
|Prophylaxis Following MI
|Prophylaxis Following MI
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|Hypertension: Class IA <cite>Esc2</cite>
|Hypertension: Class IA <cite>Esc2</cite>


Hypertension in diabetics: Class IA  <cite>Esc4</cite>
Hypertension in diabetics: Class IA  <cite>Esc3</cite>
|rowspan="3" valign="top"|Gastro-intestinal disturbances (<3%), dizziness (14%), angina, palpitation, oedema, dyspnoea, headache (14%), malaise, urticaria, pruritus, rash;
|rowspan="3" valign="top"|Gastro-intestinal disturbances (<3%), dizziness (14%), angina, palpitation, oedema, dyspnoea, headache (14%), malaise, urticaria, pruritus, rash;
|-
|-
|Left ventricular hypertrophy
|Left ventricular hypertrophy
|Losartan: 12.5-150mg daily
|Losartan: 12.5-150mg daily
|LVH:  Class IB  <cite>Esc8</cite>
|LVH:  Class IB  <cite>Esc4</cite>
|-
|-
|Diabetic nephropathy
|Diabetic nephropathy
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|Angina
|Angina
|Atenolol: 100mg once/twice daily
|Atenolol: 100mg once/twice daily
|ACS: Class IIaB <cite>Esc9</cite>
|ACS: Class IIaB <cite>Esc2</cite>


Angina in symptomatic (NYHA class II-IV) HF and LVD: Class IA <cite>Esc10</cite>
Angina in symptomatic (NYHA class II-IV) HF and LVD: Class IA <cite>Esc1</cite>
|-
|-
|Arrhythmias
|Arrhythmias
|Atenolol: 50-100mg daily
|Atenolol: 50-100mg daily
|Atrial fibrillation: Class IA; Polymorphic VT: Class IB <cite>Esc11</cite>
|Atrial fibrillation: Class IA; Polymorphic VT: Class IB <cite>Esc4</cite>


Symptomatic (NYHA class II-IV) HF, LVD and AF: Class IA; Management of VA in HF: Class IA <cite>Esc12</cite>
Symptomatic (NYHA class II-IV) HF, LVD and AF: Class IA; Management of VA in HF: Class IA <cite>Esc1</cite>


SVT: Class IIbC; Wide QRS-complex tachycardia of unknown origin: Class IIIC; Sinus tachycardia: Class IC; Poorly tolerated AVNRT with haemodynamic intolerance: Class IIaC; Recurrent symptomatic AVNRT: Class IC; Documented PSVT with only dual AV-nodal pathways or single echo beats demonstrated during electrophysiological study and no other identified cause of arrhythmia: Class IC; Infrequent, well tolerated AVNRT: Class IB; Focal junction tachycardia: Class IIaC; Nonparoxysmal junctional tachycardia: Class IIaC; WPW Syndrome: Class IIaC; AVRT, poorly tolerated: Class IIbC; Since or infrequent AVRT episode(s): Class IIaB; Acute treatment of Focal Atrial Tachycardia: Class IIaC; Prophylactic therapy for AT: Class IC; AF (Poorly tolerated): Class IIaC; AF (Stable flutter): Class IC; Prophylaxis of SVT during pregnancy: Class IIaB <cite>Acc13</cite>
SVT: Class IIbC; Wide QRS-complex tachycardia of unknown origin: Class IIIC; Sinus tachycardia: Class IC; Poorly tolerated AVNRT with haemodynamic intolerance: Class IIaC; Recurrent symptomatic AVNRT: Class IC; Documented PSVT with only dual AV-nodal pathways or single echo beats demonstrated during electrophysiological study and no other identified cause of arrhythmia: Class IC; Infrequent, well tolerated AVNRT: Class IB; Focal junction tachycardia: Class IIaC; Nonparoxysmal junctional tachycardia: Class IIaC; WPW Syndrome: Class IIaC; AVRT, poorly tolerated: Class IIbC; Since or infrequent AVRT episode(s): Class IIaB; Acute treatment of Focal Atrial Tachycardia: Class IIaC; Prophylactic therapy for AT: Class IC; AF (Poorly tolerated): Class IIaC; AF (Stable flutter): Class IC; Prophylaxis of SVT during pregnancy: Class IIaB <cite>Acc5</cite>
|-
|-
|Migraine
|Migraine
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|Hypertension
|Hypertension
|Nifedipine: 20-30mg once daily
|Nifedipine: 20-30mg once daily
|Hypertension in symptomatic (NYHA class II-IV) HF and LVD: Class IA <cite>Esc3</cite>
|Hypertension in symptomatic (NYHA class II-IV) HF and LVD: Class IA <cite>Esc1</cite>
|rowspan="3" valign="top"|Gastro-intestinal disturbance (2-11%); hypotension (1-5%), oedema (7-29%), vasodilatation, palpitation; headache (7-35%), dizziness (3-27%), lethargy (4-6%), asthenia (10-12%); less commonly tachycardia (<1-7%), syncope (<1%), chills, nasal congestion, dyspnoea (<3%), anxiety, sleep disturbance (<2%), vertigo (<3%), migraine, paraesthesia, tremor (1-8%), polyuria, dysuria, nocturia, erectile dysfunction (<2%), epistaxis, myalgia, joint swelling, visual disturbance (<2%), sweating (<2%), hypersensitivity reactions (<1%); rarely anorexia, gum hyperplasia, mood disturbances, hyperglycaemia, male infertility, purpura (<1%), and photosensitivity reactions (<1%); also reported dysphagia, intestinal obstruction, intestinal ulcer, bezoar formation, gynaecomastia, agranulocytosis, and anaphylaxis;
|rowspan="3" valign="top"|Gastro-intestinal disturbance (2-11%); hypotension (1-5%), oedema (7-29%), vasodilatation, palpitation; headache (7-35%), dizziness (3-27%), lethargy (4-6%), asthenia (10-12%); less commonly tachycardia (<1-7%), syncope (<1%), chills, nasal congestion, dyspnoea (<3%), anxiety, sleep disturbance (<2%), vertigo (<3%), migraine, paraesthesia, tremor (1-8%), polyuria, dysuria, nocturia, erectile dysfunction (<2%), epistaxis, myalgia, joint swelling, visual disturbance (<2%), sweating (<2%), hypersensitivity reactions (<1%); rarely anorexia, gum hyperplasia, mood disturbances, hyperglycaemia, male infertility, purpura (<1%), and photosensitivity reactions (<1%); also reported dysphagia, intestinal obstruction, intestinal ulcer, bezoar formation, gynaecomastia, agranulocytosis, and anaphylaxis;
|-
|-
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|Angina (prophylaxis)
|Angina (prophylaxis)
|Nifedipine: 5-20mg 3 times daily
|Nifedipine: 5-20mg 3 times daily
|Angina in symptomatic (NYHA class II-IV) HF and LVD: Class IIaA <cite>Esc14</cite>
|Angina in symptomatic (NYHA class II-IV) HF and LVD: Class IIaA <cite>Esc1</cite>
|-
|-
|colspan="6" bgcolor="#E6E6FA"|'''Anti-Arrhythmics'''
|colspan="6" bgcolor="#E6E6FA"|'''Anti-Arrhythmics'''
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|Ventricular Arrhythmias
|Ventricular Arrhythmias
|Flecainide: 50-100mg twice daily
|Flecainide: 50-100mg twice daily
|Sustained VT and VF: Class IIbC <cite>Esc15</cite>
|Sustained VT and VF: Class IIbC <cite>Esc4</cite>


Pre-excited SVT/AF: Class IB; Wide QRS-complex tachycardia of unknown origin: Lidocaine (Class IIbB) / Procainamide (Class IB); Wide QRS-complex tachycardia of unknown origin with LVD: Class IB; Focal junction tachycardia: Class IIaC; WPW Syndrome: IIaC; AVRT, poorly tolerated: IIaC; Single or infrequent AVRT episode(s): Class IIbC; Acute treatment of Focal Atrial Tachycardia: Class IIaC; Prophylactic therapy for AT: Class IIaC; AF (Stable flutter): Class IIbA; Prophylaxis of SVT during pregnancy: Class IIbB <cite>Acc16</cite>
Pre-excited SVT/AF: Class IB; Wide QRS-complex tachycardia of unknown origin: Lidocaine (Class IIbB) / Procainamide (Class IB); Wide QRS-complex tachycardia of unknown origin with LVD: Class IB; Focal junction tachycardia: Class IIaC; WPW Syndrome: IIaC; AVRT, poorly tolerated: IIaC; Single or infrequent AVRT episode(s): Class IIbC; Acute treatment of Focal Atrial Tachycardia: Class IIaC; Prophylactic therapy for AT: Class IIaC; AF (Stable flutter): Class IIbA; Prophylaxis of SVT during pregnancy: Class IIbB <cite>Acc5</cite>
|Oedema, pro-arrhythmic effects (1-13%); dyspnoea; nervous-system side-effects including dizziness, asthenia, fatigue, fever; visual disturbances (13-28%); rarely pneumonitis, hallucinations, depression, confusion, amnesia, dyskinesia, convulsions, peripheral neuropathy; also reported gastro-intestinal disturbances (1-4%), anorexia, hepatic dysfunction, flushing, syncope, drowsiness, tremor, vertigo, headache, anxiety, insomnia, ataxia, paraesthesia, anaemia, leucopenia, thrombocytopenia, corneal deposits, tinnitus, increased antinuclear antibodies, hypersensitivity reactions (including rash, urticaria, and photosensitivity), increased sweating.
|Oedema, pro-arrhythmic effects (1-13%); dyspnoea; nervous-system side-effects including dizziness, asthenia, fatigue, fever; visual disturbances (13-28%); rarely pneumonitis, hallucinations, depression, confusion, amnesia, dyskinesia, convulsions, peripheral neuropathy; also reported gastro-intestinal disturbances (1-4%), anorexia, hepatic dysfunction, flushing, syncope, drowsiness, tremor, vertigo, headache, anxiety, insomnia, ataxia, paraesthesia, anaemia, leucopenia, thrombocytopenia, corneal deposits, tinnitus, increased antinuclear antibodies, hypersensitivity reactions (including rash, urticaria, and photosensitivity), increased sweating.
|-
|-
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|Ventricular, Arrhythmias
|Ventricular, Arrhythmias
|Amiodarone: 200mg 2-3 times daily
|Amiodarone: 200mg 2-3 times daily
|Sustained VT and VF: Class IIaC; Polymorphic VT: Class IC <cite>Esc17</cite>
|Sustained VT and VF: Class IIaC; Polymorphic VT: Class IC <cite>Esc4</cite>


Management of VA in HF: Class IA; Prevention of VA in HF: Class IIbB <cite>Esc18</cite>
Management of VA in HF: Class IA; Prevention of VA in HF: Class IIbB <cite>Esc1</cite>


SVT: Class IIBC; Wide QRS-complex tachycardia of unknown origin: Class IB; Wide QRS-complex tachycardia of unknown origin with LVD: Class IB; Recurrent AVNRT unresponsive to beta blocker or calcium-channel blocker and patient not desiring RF ablation: Class IIbC; Focal junction tachycardia: Class IIaC; WPW Syndrome: IIaC; AVRT, poorly tolerated: Class IIaC; Since or infrequent AVRT episode(s): Class IIbB; Acute treatment of Focal Atrial Tachycardia: Class IIaC; Prophylactic therapy for AT: Class IIaC; AF (Poorly tolerated): Class IIbC; AF (Stable flutter): Class IIbC; Prophylaxis of SVT during pregnancy: Class IIIC <cite>Acc19</cite>
SVT: Class IIBC; Wide QRS-complex tachycardia of unknown origin: Class IB; Wide QRS-complex tachycardia of unknown origin with LVD: Class IB; Recurrent AVNRT unresponsive to beta blocker or calcium-channel blocker and patient not desiring RF ablation: Class IIbC; Focal junction tachycardia: Class IIaC; WPW Syndrome: IIaC; AVRT, poorly tolerated: Class IIaC; Since or infrequent AVRT episode(s): Class IIbB; Acute treatment of Focal Atrial Tachycardia: Class IIaC; Prophylactic therapy for AT: Class IIaC; AF (Poorly tolerated): Class IIbC; AF (Stable flutter): Class IIbC; Prophylaxis of SVT during pregnancy: Class IIIC <cite>Acc5</cite>
|Gastro-intestinal disturbances (2-20%)), taste disturbances, hepatic disturbances (up to 50%); bradycardia; pulmonary toxicity (1-17%); tremor (9-59%), sleep disorders; hypothyroidism (5-10%), hyperthyroidism (5-10%); reversible corneal microdeposits (up to 98%); phototoxicity, persistent slate-grey skin discoloration (1-7%), injection-site reactions; less commonly onset or worsening of arrhythmia, conduction disturbances, peripheral neuropathy (1-105) and myopathy; very rarely sinus arrest, bronchospasm, ataxia (2-37%), benign intracranial hypertension, headache, vertigo, epididymo-orchitis, impotence, haemolytic or aplastic anaemia, thrombocytopenia, rash, hypersensitivity including photosensitivity (2-20%), anaphylaxis on rapid injection, hypotension (10-30%), respiratory distress syndrome, sweating, and hot flushes
|Gastro-intestinal disturbances (2-20%)), taste disturbances, hepatic disturbances (up to 50%); bradycardia; pulmonary toxicity (1-17%); tremor (9-59%), sleep disorders; hypothyroidism (5-10%), hyperthyroidism (5-10%); reversible corneal microdeposits (up to 98%); phototoxicity, persistent slate-grey skin discoloration (1-7%), injection-site reactions; less commonly onset or worsening of arrhythmia, conduction disturbances, peripheral neuropathy (1-105) and myopathy; very rarely sinus arrest, bronchospasm, ataxia (2-37%), benign intracranial hypertension, headache, vertigo, epididymo-orchitis, impotence, haemolytic or aplastic anaemia, thrombocytopenia, rash, hypersensitivity including photosensitivity (2-20%), anaphylaxis on rapid injection, hypotension (10-30%), respiratory distress syndrome, sweating, and hot flushes
|-
|-
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|Supra-ventricular Arrhythmias
|Supra-ventricular Arrhythmias
|Acute: 0.75-1.5mg over 24 hours; Maintenance: 125-150µg daily
|Acute: 0.75-1.5mg over 24 hours; Maintenance: 125-150µg daily
|SVT: Class IIbC; WPW Syndrome: Class IIIC; AVRT, poorly tolerated: Class IIIC; Since or infrequent AVRT episode(s): Class IIIC; Prophylaxis of SVT during pregnancy: Class IC <cite>Acc20</cite>
|SVT: Class IIbC; WPW Syndrome: Class IIIC; AVRT, poorly tolerated: Class IIIC; Since or infrequent AVRT episode(s): Class IIIC; Prophylaxis of SVT during pregnancy: Class IC <cite>Acc5</cite>
|rowspan="3" valign="top"|Gastro-intestinal disturbances (vomiting, diarrhoea, anorexia, abdominal pain) (25%); arrhythmias (up to 50%), AV conduction disturbances (50%); nervous system disturbances (dizziness, apathy, confusion, headache, fatigue, weakness) (25%); blurred or yellow vision; rash, eosinophilia, depression, anorexia, intestinal ischaemia and necrosis, psychosis, gynaecomastia on long-term use, and thrombocytopenia.
|rowspan="3" valign="top"|Gastro-intestinal disturbances (vomiting, diarrhoea, anorexia, abdominal pain) (25%); arrhythmias (up to 50%), AV conduction disturbances (50%); nervous system disturbances (dizziness, apathy, confusion, headache, fatigue, weakness) (25%); blurred or yellow vision; rash, eosinophilia, depression, anorexia, intestinal ischaemia and necrosis, psychosis, gynaecomastia on long-term use, and thrombocytopenia.
|-
|-
|Heart Failure
|Heart Failure
|62.5-125 µg daily
|62.5-125 µg daily
|Symptomatic (NYHA class II-IV) HF: Class IIbB <cite>Esc21</cite>
|Symptomatic (NYHA class II-IV) HF: Class IIbB


Symptomatic (NYHA class II-IV) HF, LVD and AF: Class IB; Acute HF with AF and VT: Class IC <cite>Esc22</cite>
Symptomatic (NYHA class II-IV) HF, LVD and AF: Class IB; Acute HF with AF and VT: Class IC <cite>Esc1</cite>
|-
|-
|colspan="6" bgcolor="#E6E6FA"|'''Anti-platelet Drugs'''
|colspan="6" bgcolor="#E6E6FA"|'''Anti-platelet Drugs'''
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|Prevention of thrombotic cerebro- or cardio-vascular disease
|Prevention of thrombotic cerebro- or cardio-vascular disease
|75mg once/day
|75mg once/day
|Prevention in AF: Class IC; Prevention in diabetic patients: IIaB <cite>Esc23</cite>
|Prevention in AF: Class IC; Prevention in diabetic patients: IIaB <cite>Esc2</cite>


Prevention in Symptomatic (NYHA class II-IV) HF and AF: Class IIA <cite>Esc24</cite>
Prevention in Symptomatic (NYHA class II-IV) HF and AF: Class IIA <cite>Esc1</cite>


Prevention in hypertensive patients with CV events: Class IA; Prevention in hypertensive patients without CV history but with reduced renal function/high risk: Class IIbA <cite>Esc25</cite>
Prevention in hypertensive patients with CV events: Class IA; Prevention in hypertensive patients without CV history but with reduced renal function/high risk: Class IIbA <cite>Esc3</cite>


Post-MI: Class Ia <cite>Esc26</cite>
Post-MI: Class Ia <cite>Esc3</cite>
|rowspan="2" valign="top"|Bronchospasm (10-30% in asthmatics); gastro-intestinal irritation (up to 83%), gastro-intestinal haemorrhage (occasionally major), also other haemorrhage (e.g. intracranial (0.5%), subconjunctival), chest pain (8.3%), oedema (4.5%), hypertension (4.3%).
|rowspan="2" valign="top"|Bronchospasm (10-30% in asthmatics); gastro-intestinal irritation (up to 83%), gastro-intestinal haemorrhage (occasionally major), also other haemorrhage (e.g. intracranial (0.5%), subconjunctival), chest pain (8.3%), oedema (4.5%), hypertension (4.3%).
|-
|-
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|Prevention of thrombotic events (esp. when warfarin not tolerated)
|Prevention of thrombotic events (esp. when warfarin not tolerated)
|75mg once/day
|75mg once/day
|Prevention in diabetic patients: IIaB; Primary and secondary prevention of stroke: Class IB <cite>Esc27</cite>
|Prevention in diabetic patients: IIaB; Primary and secondary prevention of stroke: Class IB <cite>Esc2</cite>


Prevention in Symptomatic (NYHA class II-IV) HF and AF: Class IIA <cite>Esc24</cite>
Prevention in Symptomatic (NYHA class II-IV) HF and AF: Class IIA <cite>Esc1</cite>


Acute phase of coronary artery syndrome: Class IB; Non-cardioembolic cerebral ischaemic events: Class IA <cite>Esc28</cite>
Acute phase of coronary artery syndrome: Class IB; Non-cardioembolic cerebral ischaemic events: Class IA <cite>Esc3</cite>
|rowspan="3" valign="top"|Dyspepsia (5.2%), abdominal pain (5.6%), diarrhoea (4.5%); bleeding disorders including gastro-intestinal (2.0%) and intracranial (0.4%), nausea (3.4%), vomiting, gastritis, flatulence, constipation, gastric and duodenal ulcers, headache (7.6%), epistaxis (2.9%), dizziness (6.2%), paraesthesia, leucopenia, decreased platelets (very rarely severe thrombocytopenia), eosinophilia, rash (4.2%), pruritus (3.3%), vertigo, colitis, pancreatitis, hepatitis (<1%), acute liver failure, hypertension (4.3%), chest pain (8.3%), oedema (4.1%), vasculitis, confusion, hallucinations, taste disturbance, cough (3.9%), fatigue (4.8%) stomatitis, bronchospasm, interstitial pneumonitis, pyrexia (2.2%), blood disorders including thrombocytopenic purpura (5.3%), agranulocytosis, neutropenia (0.04%) and pancytopenia and hypersensitivity-like reactions (<0.1%)including fever, glomerulonephritis, arthralgia, Stevens-Johnson syndrome, toxic epidermal necrolysis, lichen planus.
|rowspan="3" valign="top"|Dyspepsia (5.2%), abdominal pain (5.6%), diarrhoea (4.5%); bleeding disorders including gastro-intestinal (2.0%) and intracranial (0.4%), nausea (3.4%), vomiting, gastritis, flatulence, constipation, gastric and duodenal ulcers, headache (7.6%), epistaxis (2.9%), dizziness (6.2%), paraesthesia, leucopenia, decreased platelets (very rarely severe thrombocytopenia), eosinophilia, rash (4.2%), pruritus (3.3%), vertigo, colitis, pancreatitis, hepatitis (<1%), acute liver failure, hypertension (4.3%), chest pain (8.3%), oedema (4.1%), vasculitis, confusion, hallucinations, taste disturbance, cough (3.9%), fatigue (4.8%) stomatitis, bronchospasm, interstitial pneumonitis, pyrexia (2.2%), blood disorders including thrombocytopenic purpura (5.3%), agranulocytosis, neutropenia (0.04%) and pancytopenia and hypersensitivity-like reactions (<0.1%)including fever, glomerulonephritis, arthralgia, Stevens-Johnson syndrome, toxic epidermal necrolysis, lichen planus.
|-
|-
|Acute myocardial infarction
|Acute myocardial infarction
|300mg daily initially then 75mg once/day
|300mg daily initially then 75mg once/day
|Post STEMI: Class IA <cite>Esc5</cite>
|Post STEMI: Class IA <cite>Esc4</cite>
|-
|-
|Acute coronary syndrome
|Acute coronary syndrome
|300mg daily initially then 75mg once/day
|300mg daily initially then 75mg once/day
|ACS: Class IIaC <cite>Esc29</cite>
|ACS: Class IIaC <cite>Esc2</cite>
|-
|-
|Prasugrel
|Prasugrel
|Prevention of thrombotic events.
|Prevention of thrombotic events.
|60mg bolus then 5-10mg once daily
|60mg bolus then 5-10mg once daily
|Prevention in Symptomatic (NYHA class II-IV) HF and AF: Class IIA <cite>Esc24</cite>
|Prevention in Symptomatic (NYHA class II-IV) HF and AF: Class IIA <cite>Esc1</cite>


Acute phase of coronary artery syndrome: Class IB <cite>Esc30</cite>
Acute phase of coronary artery syndrome: Class IB <cite>Esc3</cite>
|Haemorrhage (11.3%) (including gastro-intestinal (1.5%) and intracranial), haematoma, haematuria, hypertension (7.5%), hypotension (3.9%), headache (5.5%), back pain (5.0%), dyspnoea (4.9%), nausea (4.6%), dizziness (4.1%), cough (3.9%), fatigue (3.7%), chest pain (3.1%), arrhythmias including atrial fibrillation (2.9%) and bradycardia (2.9%), rash (2.8%), pyrexia (2.7%), oedema (2.7%), diarrhoea (2.3%), hypercholesterolaemia/hyperlipidaemia (7.5%), anaemia, rash,hypersensitivity reactions including angioedema (0.06%), thrombocytopenia (0.06%), thrombotic thrombocytopenic purpura.
|Haemorrhage (11.3%) (including gastro-intestinal (1.5%) and intracranial), haematoma, haematuria, hypertension (7.5%), hypotension (3.9%), headache (5.5%), back pain (5.0%), dyspnoea (4.9%), nausea (4.6%), dizziness (4.1%), cough (3.9%), fatigue (3.7%), chest pain (3.1%), arrhythmias including atrial fibrillation (2.9%) and bradycardia (2.9%), rash (2.8%), pyrexia (2.7%), oedema (2.7%), diarrhoea (2.3%), hypercholesterolaemia/hyperlipidaemia (7.5%), anaemia, rash,hypersensitivity reactions including angioedema (0.06%), thrombocytopenia (0.06%), thrombotic thrombocytopenic purpura.
|-
|-
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|Prevention of thrombotic events.
|Prevention of thrombotic events.
|180mg bolus then 90mg twice daily
|180mg bolus then 90mg twice daily
|Prevention in Symptomatic (NYHA class II-IV) HF and AF: Class IIA <cite>Esc24</cite>
|Prevention in Symptomatic (NYHA class II-IV) HF and AF: Class IIA <cite>Esc1</cite>


Acute phase of coronary artery syndrome: Class IB <cite>Esc30</cite>
Acute phase of coronary artery syndrome: Class IB <cite>Esc3</cite>
|Dyspnoea (13.8%), haemorrhage, bruising; nausea (4.3%), vomiting, diarrhoea (3.7%), hypertension (3.8%), hypotension (3.2%), back pain (3.6%), abdominal pain, dyspepsia, gastritis, dizziness (4.5%), chest pain (3.7%), headache (6.5%), cough (4.9%), rash, pruritus, fatigue (3.2%),  constipation, arrhythmias including atrial fibrillation (4.2%), paraesthesia, confusion, hyperuricaemia, raised serum creatinine (7.4%), vertigo.
|Dyspnoea (13.8%), haemorrhage, bruising; nausea (4.3%), vomiting, diarrhoea (3.7%), hypertension (3.8%), hypotension (3.2%), back pain (3.6%), abdominal pain, dyspepsia, gastritis, dizziness (4.5%), chest pain (3.7%), headache (6.5%), cough (4.9%), rash, pruritus, fatigue (3.2%),  constipation, arrhythmias including atrial fibrillation (4.2%), paraesthesia, confusion, hyperuricaemia, raised serum creatinine (7.4%), vertigo.
|-
|-
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|Primary hyper-cholesterolaemia, combined hyperlipidaemia
|Primary hyper-cholesterolaemia, combined hyperlipidaemia
|Simvastatin: 10-20mg once daily
|Simvastatin: 10-20mg once daily
|Dyslipidaemia: Class IA; Low HDL-C: Class IIbB; Elderly patients with CVD: IB; Elderly patients with no CVD but CV risk factors: IIbB; Type I diabetes: IC; Patients with CKD: IIaC; Transplant patients: Class IIaB; PAD: Class IA; HIV patients: IIaC <cite>Esc31</cite>
|Dyslipidaemia: Class IA; Low HDL-C: Class IIbB; Elderly patients with CVD: IB; Elderly patients with no CVD but CV risk factors: IIbB; Type I diabetes: IC; Patients with CKD: IIaC; Transplant patients: Class IIaB; PAD: Class IA; HIV patients: IIaC <cite>Esc2</cite>


Hypertension in diabetics: Class IA; ACS: Class IA <cite>Esc32</cite>
Hypertension in diabetics: Class IA; ACS: Class IA <cite>Esc3</cite>
|rowspan="3" valign="top"|Oedema (2.7%), abdominal pain (5.9%), nausea (5.4%), atrial fibrillation (5.7%), constipation (2.2%), gastritis (4.9%), diabetes mellitus (4.2%), myalgia (3.7%), headache (2.5%), insomnia (4.0%), vertigo (4.5%), bronchitis (6.6%), sinusitis (2.3%), eczema (4.5%), urinary tract infection (3.2%)
|rowspan="3" valign="top"|Oedema (2.7%), abdominal pain (5.9%), nausea (5.4%), atrial fibrillation (5.7%), constipation (2.2%), gastritis (4.9%), diabetes mellitus (4.2%), myalgia (3.7%), headache (2.5%), insomnia (4.0%), vertigo (4.5%), bronchitis (6.6%), sinusitis (2.3%), eczema (4.5%), urinary tract infection (3.2%)
|-
|-
|Familial hyper-cholesterolaemia
|Familial hyper-cholesterolaemia
|Simvastatin: 40mg once daily
|Simvastatin: 40mg once daily
|HeFH: Class IC <cite>Esc33</cite>
|HeFH: Class IC <cite>Esc2</cite>
|-
|-
|Prevention of cardiovascular events
|Prevention of cardiovascular events
|20-40mg once daily
|20-40mg once daily
|Class IA <cite>Esc34</cite>
|Class IA <cite>Esc2</cite>
|-
|-
|rowspan="2"|Fibrates
|rowspan="2"|Fibrates
Line 583: Line 585:
|Hyperlipidaemias of types IIa, IIb, III, IV and V  
|Hyperlipidaemias of types IIa, IIb, III, IV and V  
|Gemfibrozil: 0.9-1.2mg daily
|Gemfibrozil: 0.9-1.2mg daily
|Low HDL-C: Class IIbB; Transplant patients (with HTG, low HDL-C): Class IIbC <cite>Esc36</cite>
|Low HDL-C: Class IIbB; Transplant patients (with HTG, low HDL-C): Class IIbC <cite>Esc6</cite>
|Gastro-intestinal disturbances including dyspepsia (19.6%), nausea (4%), abdominal pain (9.8%), diarrhoea (7.2%), vomiting (1.2%); headache (1.2%), fatigue (3.8%), vertigo (1.5%), eczema, rash (1.7%), atrial fibrillation (0.7%), pancreatitis, appendicitis, disturbances in liver function including hepatitis and cholestatic jaundice, dizziness, paraesthesia, sexual dysfunction, thrombocytopenia, anaemia, leucopenia, eosinophilia, bone-marrow suppression, myalgia, myopathy, myasthenia, myositis accompanied by increase in creatine kinase, blurred vision, exfoliative dermatitis, alopecia, and photosensitivity
|Gastro-intestinal disturbances including dyspepsia (19.6%), nausea (4%), abdominal pain (9.8%), diarrhoea (7.2%), vomiting (1.2%); headache (1.2%), fatigue (3.8%), vertigo (1.5%), eczema, rash (1.7%), atrial fibrillation (0.7%), pancreatitis, appendicitis, disturbances in liver function including hepatitis and cholestatic jaundice, dizziness, paraesthesia, sexual dysfunction, thrombocytopenia, anaemia, leucopenia, eosinophilia, bone-marrow suppression, myalgia, myopathy, myasthenia, myositis accompanied by increase in creatine kinase, blurred vision, exfoliative dermatitis, alopecia, and photosensitivity
|-
|-
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|Primary and familial hyper-cholesterolaemia
|Primary and familial hyper-cholesterolaemia
|10mg once daily
|10mg once daily
|Transplant patients (with high LDL-C): Class IIbC <cite>Esc35</cite>
|Transplant patients (with high LDL-C): Class IIbC <cite>Esc6</cite>
|Gastro-intestinal disturbance including diarrhoea (4.1%) and abdominal pain (3.0%); headache, fatigue (2.4%); myalgia, arthralgia (3.0%), sinusitis (3.6%), pharyngitis (2.3%), viral infection (2.2%), coughing (2.3%), hypersensitivity reactions including rash, angioedema, and anaphylaxis, hepatitis,pancreatitis, cholelithiasis, cholecystitis, thrombocytopenia, raised creatine kinase, myopathy, and rhabdomyolysis
|Gastro-intestinal disturbance including diarrhoea (4.1%) and abdominal pain (3.0%); headache, fatigue (2.4%); myalgia, arthralgia (3.0%), sinusitis (3.6%), pharyngitis (2.3%), viral infection (2.2%), coughing (2.3%), hypersensitivity reactions including rash, angioedema, and anaphylaxis, hepatitis,pancreatitis, cholelithiasis, cholecystitis, thrombocytopenia, raised creatine kinase, myopathy, and rhabdomyolysis
|}
|}
Line 595: Line 597:
==References==
==References==
<biblio>
<biblio>
#Esc1 ESC Guidelines (European Heart Journal doi:10.1093/eurheartj/ehs104): Hypertension in symptomatic (NYHA class II-IV) HF and LVD: Class IC
#Esc1 pmid=22611136
#Esc2 ESC and EASD Guidelines (European Heart Journal doi: 10.1093/eurheart/ehl261): Hypertension: Class IA
#Esc2 pmid=17220161
#Esc3 ESC Guidelines (European Heart Journal doi:10.1093/eurheartj/ehs104): Hypertension in symptomatic (NYHA class II-IV) HF and LVD: Class IA
#Esc3 pmid=22555213
#Esc4 ESC Guidelines: (European Heart Journal doi:10.1093/eurheartj/ehs092):Hypertension in diabetics: Class IA
#Esc4 pmid=22922416
#Esc5 ESC Guidelines (European Heart Journal (2012) 33, 2569–2619 doi:10.1093/eurheartj/ehs215): Post STEMI: Class IA
#Acc5 pmid=14557344
#Esc6 ESC and EASD Guidelines (European Heart Journal doi: 10.1093/eurheart/ehl261): Diabetic patients: Class IC
#Esc6 pmid=21712404
#Esc7 ESC Guidelines (European Heart Journal doi:10.1093/eurheartj/ehs104): Symptomatic (NYHA class II-IV) HF: Class IA; Acute heart failure with ACS: Class IA
#Esc8 ESC Guidelines (European Heart Journal (2012) 33, 2569–2619 doi:10.1093/eurheartj/ehs215): LVH: Class IB
#Esc9 ESC and EASD Guidelines (European Heart Journal doi: 10.1093/eurheart/ehl261) ACS: Class IIaB
#Esc10 ESC Guidelines (European Heart Journal doi:10.1093/eurheartj/ehs104): Angina in symptomatic (NYHA class II-IV) HF and LVD: Class IA
#Esc11 ESC Guidelines (European Heart Journal (2012) 33, 2569–2619 doi:10.1093/eurheartj/ehs215): Atrial fibrillation: Class IA; Polymorphic VT: Class IB
#Esc12 ESC Guidelines (European Heart Journal doi:10.1093/eurheartj/ehs104): Symptomatic (NYHA class II-IV) HF, LVD and AF: Class IA; Management of VA in HF: Class IA
#Acc13 ACC/AHA/ESC Guidelines (Blomström-Lundqvist and Scheinman et al. 2003): SVT: Class IIbC; Wide QRS-complex tachycardia of unknown origin: Class IIIC; Sinus tachycardia: Class IC; Poorly tolerated AVNRT with haemodynamic intolerance: Class IIaC; Recurrent symptomatic AVNRT: Class IC; Documented PSVT with only dual AV-nodal pathways or single echo beats demonstrated during electrophysiological study and no other identified cause of arrhythmia: Class IC; Infrequent, well tolerated AVNRT: Class IB; Focal junction tachycardia: Class IIaC; Nonparoxysmal junctional tachycardia: Class IIaC; WPW Syndrome: Class IIaC; AVRT, poorly tolerated: Class IIbC; Since or infrequent AVRT episode(s): Class IIaB; Acute treatment of Focal Atrial Tachycardia: Class IIaC; Prophylactic therapy for AT: Class IC; AF (Poorly tolerated): Class IIaC; AF (Stable flutter): Class IC; Prophylaxis of SVT during pregnancy: Class IIaB
#Esc14 ESC Guidelines (European Heart Journal doi:10.1093/eurheartj/ehs104): Angina in symptomatic (NYHA class II-IV) HF and LVD: Class IIaA
#Esc15 ESC Guidelines(European Heart Journal (2012) 33, 2569–2619 doi:10.1093/eurheartj/ehs215): Sustained VT and VF: Class IIbC
#Acc16 ACC/AHA/ESC Guidelines (Blomström-Lundqvist and Scheinman et al. 2003): Pre-excited SVT/AF: Class IB; Wide QRS-complex tachycardia of unknown origin: Lidocaine (Class IIbB) / Procainamide (Class IB); Wide QRS-complex tachycardia of unknown origin with LVD: Class IB; Focal junction tachycardia: Class IIaC; WPW Syndrome: IIaC; AVRT, poorly tolerated: IIaC; Single or infrequent AVRT episode(s): Class IIbC; Acute treatment of Focal Atrial Tachycardia: Class IIaC; Prophylactic therapy for AT: Class IIaC; AF (Stable flutter): Class IIbA; Prophylaxis of SVT during pregnancy: Class IIbB
#Esc17 ESC Guidelines(European Heart Journal (2012) 33, 2569–2619 doi:10.1093/eurheartj/ehs215): Sustained VT and VF: Class IIaC; Polymorphic VT: Class IC
#Esc18 ESC Guidelines (European Heart Journal doi:10.1093/eurheartj/ehs104): Management of VA in HF: Class IA; Prevention of VA in HF: Class IIbB
#Acc19 ACC/AHA/ESC Guidelines (Blomström-Lundqvist and Scheinman et al. 2003): SVT: Class IIBC; Wide QRS-complex tachycardia of unknown origin: Class IB; Wide QRS-complex tachycardia of unknown origin with LVD: Class IB; Recurrent AVNRT unresponsive to beta blocker or calcium-channel blocker and patient not desiring RF ablation: Class IIbC; Focal junction tachycardia: Class IIaC; WPW Syndrome: IIaC; AVRT, poorly tolerated: Class IIaC; Since or infrequent AVRT episode(s): Class IIbB; Acute treatment of Focal Atrial Tachycardia: Class IIaC; Prophylactic therapy for AT: Class IIaC; AF (Poorly tolerated): Class IIbC; AF (Stable flutter): Class IIbC; Prophylaxis of SVT during pregnancy: Class IIIC
#Acc20 ACC/AHA/ESC Guidelines (Blomström-Lundqvist and Scheinman et al. 2003): SVT: Class IIbC; WPW Syndrome: Class IIIC; AVRT, poorly tolerated: Class IIIC; Since or infrequent AVRT episode(s): Class IIIC; Prophylaxis of SVT during pregnancy: Class IC
#Esc21 ESC Guidelines (European Heart Journal doi:10.1093/eurheartj/ehs104): Symptomatic (NYHA class II-IV) HF: Class IIbB
#Esc22 ESC Guidelines Symptomatic (NYHA class II-IV) HF, LVD and AF: Class IB; Acute HF with AF and VT: Class IC
#Esc23 ESC and EASD Guidelines (European Heart Journal doi: 10.1093/eurheart/ehl261): Prevention in AF: Class IC; Prevention in diabetic patients: IIaB
#Esc24 ESC Guidelines (European Heart Journal doi:10.1093/eurheartj/ehs104): Prevention in Symptomatic (NYHA class II-IV) HF and AF: Class IIA
#Esc25 ESC Guidelines: (European Heart Journal doi:10.1093/eurheartj/ehs092): Prevention in hypertensive patients with CV events: Class IA; Prevention in hypertensive patients without CV history but with reduced renal function/high risk: Class IIbA
#Esc26 ESC Guidelines: (European Heart Journal doi:10.1093/eurheartj/ehs092): Post-MI: Class Ia
#Esc27 ESC and EASD Guidelines (European Heart Journal doi:10.1093/eurheart/ehl261): Prevention in diabetic patients: IIaB; Primary and secondary prevention of stroke: Class IB
#Esc28 ESC Guidelines: (European Heart Journal doi:10.1093/eurheartj/ehs092): Acute phase of coronary artery syndrome: Class IB; Non-cardioembolic cerebral ischaemic events: Class IA
#Esc29 ESC and EASD Guidelines (European Heart Journal doi: 10.1093/eurheart/ehl261): ACS: Class IIaC
#Esc30 ESC Guidelines: (European Heart Journal doi:10.1093/eurheartj/ehs092): Acute phase of coronary artery syndrome: Class IB
#Esc31 ESC and EASD Guidelines (European Heart Journal doi:10.1093/eurheart/ehl261); Dyslipidaemia: Class IA; Low HDL-C: Class IIbB; Elderly patients with CVD: IB; Elderly patients with no CVD but CV risk factors: IIbB; Type I diabetes: IC; Patients with CKD: IIaC; Transplant patients: Class IIaB; PAD: Class IA; HIV patients: IIaC
#Esc32 ESC Guidelines: (European Heart Journal doi:10.1093/eurheartj/ehs092): Hypertension in diabetics: Class IA; ACS: Class IA
#Esc33 ESC and EASD Guidelines (European Heart Journal doi: 10.1093/eurheart/ehl261): HeFH: Class IC
#Esc34 ESC and EASD Guidelines (European Heart Journal doi: 10.1093/eurheart/ehl261): Class IA
#Esc35 ESC and EAS Guidelines (European Heart Journal (2011) 32, 1769–1818 doi:10.1093/eurheartj/ehr158): Transplant patients (with high LDL-C): Class IIbC
#Esc36 ESC and EAS Guidelines (European Heart Journal (2011) 32, 1769–1818 doi:10.1093/eurheartj/ehr158): Low HDL-C: Class IIbB; Transplant patients (with HTG, low HDL-C): Class IIbC
</biblio>
</biblio>