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Antiplatelet treatment

Aspirin -AKA acetylsalicylic acid Non -selective cyclooxygenase inhibitor ( inhibits thromboxane A2 -this has role in the complications of the atheromatosis lesions ) It binds to and acetylates serine residues in cyclooxygenases leading to 
○ decreased synthesis of prostaglandin , platelet aggregation and inflammation Another mechanism has been described : the induction of production of aspirin-triggered lipoxins ( ATLs ) It is believed that ATL resolves inflammation and acts as antioxidant & immunomodulator Aspirin has analgesic , antipyretic and anticoagulant properties It does not alter coagulation tests TXA2 inhibition is irreversible ie the effect persists for the lifespan of the thrombocyte ie 7-10 days Extends bleeding time

 

THIENOPRIDINE DERIVATIVES Clopidogrel , prasugrel and ticagrelor are thienopyridine derivatives Block binding of ADP to its platelet receptor ( ADP is powerful inducer of platelet aggregation ) Interfere with ADP mediated activation of glycoprotein IIb-IIIa complex Irreversibly inhibit platelet aggregation No effect on prostaglandin metabolism Do not affect coagulation profile
( ie PT and PTT monitoring is not required )

 

DIPYRIDAMOLE – synthetic derivative of pyrimido-pyrimidine with anti-platelet properties inhibits the uptake of adenosine into erythrocytes , platelets and endothelial cell -increased adenosine conc locally to act on platelet A2 receptors which stimulates platelet adenyl cyclase and hence increase in intraplatelet cAMP -this increase in cAMP leads to inhibition of platelet aggregation in response to various stimuli as PAF ( platelet activating factor ) , collagen and ADP is inhibited It has both antiplatelet and vasodilatory properties ( vasodilatory action may lead to side effects as headache , flushing , dizziness ) It may also act by inhibiting the breakdown of cyclic guanosine monophosphate

 

examples include abciximab , eptifibatide , tirofiban Glycoprotein IIb/IIIa is a receptor located on platelet membrane -mediates platelet aggregation 
(final common pathway of platelet aggregation ) The receptors recognise an Arginine-glycine-aspartic acid sequence ( RGD ) contained in adhesive molecules as Fibrinogen and Von-villerbrand Factor Used IV in secondary care

 

INDICATIONS FOR ANTIPLATELET TREATMENT

 -CKS RECOMMENDATIONS Main indications for treatment are
 primary prevention of atherothrombotic events in people who are at high risk secondary prevention of atherothrombotic events in people with
○ acute coronary syndrome ( ACS )
○ angina
○ peripheral arterial disease
○ atrial fibrillation ( CKS add here -although anticoagulants are usually used ) secondary prevention of cardiovascular events in people after
○ myocardial infarction
○ stent implantation
○ stroke or TIA prevention of atherothrombotic events in people undergoing percutaneous coronary intervention.

 

CKS also mentions ( last reviewed August 2020 ) that do not routinely prescribe antiplatelet treatment for the primary prevention of cardiovascular disease BUT
 they may be considered in people at high risk of stroke or myocardial infarction

 

Angina aspirin 75 mg / day clopidogrel for those who cannot take aspirin

 

Atrial fibrillation – dual antiplatelet therapy ( DAPT ) can be suitable for those who are unwilling to take anticoagulants
this should be aspirin 75 mg + clopidogrel 75 mg ( daily )

 

Acute coronary syndrome – ACS which is managed medically aspirin 75 mg + ticagrelor 90 bd ( daily for 12 months )

 

Percutaneous coronary intervention ( PCI ) for ACS aspirin 75 mg with either ticagrelor 90 mg bd pr prasugrel 10 mg od use clopidogrel 75 mg if prasugrel or ticagrelor are not suitable

 

PCI in people with stable CAD aspirin 75 mg + clopidogrel 75 mg daily consider ticagrelor or prasugrel instead of clopidogrel where inappropriate

 

 

 

ACS -who are undergoing CABG aspirin 75 mg in combination with ticagrelor 90 mg bd or prasugrel 10 mg daily clopidogrel 75 mg daily -if prasugrel or ticagrelor are not suitable

 

Stroke or TIA – clopidogrel 75 mg is the choice modified release ( MR ) dipyridamole ( 200 mg bd ) combined with low dose aspirin or is unable to take MR dipyridamole -aspirin alone

 

Peripheral arterial disease or multivascular disease clopidogrel 75 mg is the agent of choice consider aspirin 75 mg if clopidogrel is unsuitable

REFERENCES

  1. CKS NHS antiplatelet treatment Antiplatelet treatment | Health topics A to Z | CKS | NICE
  2. UK Guidelines aspirin UK Guidelines for Aspirin | The International Aspirin Foundation (aspirin-foundation.com)
  3. Arif H, Aggarwal S. Salicylic Acid (Aspirin) [Updated 2021 Jul 15]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK519032/
  4. Dipyridamole | C24H40N8O4 – PubChem (nih.gov)
  5. Aspirin | HC9H7O4 – PubChem (nih.gov)
  6. CLOPIDOGREL | Drug | BNF content published by NICE

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