Antiplatelet drugs, aspirin

Common indications

1. For treatment of acute coronary syndrome and acute ischaemic stroke, where rapid inhibition of platelet aggregation can prevent or limit arterial thrombosis and reduce subsequent mortality.
2. For long-term secondary prevention of thrombotic arterial events in patients with cardiovascular, cerebrovascular and peripheral arterial disease.
3. To reduce the risk of intracardiac thrombus and embolic stroke in atrial fibrillation where warfarin and novel oral anticoagulants are contraindicated.
4. To control mild-to-moderate pain and fever (see Non-steroidal anti-inflammatory drugs, although other drugs are usually preferred, particularly in patients with inflammatory conditions).

 

Mechanisms of action

• Thrombotic events occur when platelet-rich thrombus forms in atheromatous arteries and occludes the circulation. Aspirin irreversibly inhibits cyclooxygenase (COX) to reduce production of the pro-aggregatory factor thromboxane from arachidonic acid, reducing platelet aggregation and the risk of arterial occlusion. The antiplatelet effect of aspirin occurs at low doses and lasts for the lifetime of a platelet (which does not have a nucleus to allow synthesis of new COX) and thus only wears off as new platelets are made.

 

Important adverse effects

• The most common adverse effect of aspirin is gastrointestinal irritation. More serious effects include gastrointestinal ulceration and haemorrhage and hypersensitivity reactions including bronchospasm. In regular high-dose therapy aspirin causes tinnitus. Aspirin is life-threatening in overdose. Features include hyperventilation, hearing changes, metabolic acidosis and confusion, followed by convulsions, cardiovascular collapse and respiratory arrest.

 

Warnings

• Aspirin should not be given to children aged under 16 years due to the risk of Reye’s syndrome, a rare but life-threatening illness that principally affects the liver and brain. It should not be taken by people with aspirin hypersensitivity, i.e. who have had bronchospasm or other allergic symptoms triggered by exposure to aspirin or another NSAID. However, aspirin is not routinely contraindicated in asthma. Aspirin should be avoided in the third trimester of pregnancy when prostaglandin inhibition may lead to premature closure of the ductus arteriosus. Aspirin should be used with caution in people with peptic ulceration (e.g. prescribe gastroprotection) or gout, as it may trigger an acute attack.

 

Important interactions

• Aspirin acts synergistically with other antiplatelet agents, which although therapeutically beneficial can lead to increased risk of bleeding. Thus, although it may be given with antiplatelet drugs (e.g. clopidogrel, dipyridamole) and anticoagulants (e.g. heparin, warfarin) in some situations (e.g. acute coronary syndrome), caution is required.