What it is
Acetylsalicylic acid (ASA, aspirin) is one of the oldest and most studied medicines in history. Synthesised by Bayer in 1897, it remains essential in cardiology because of its antiplatelet effect.
At low doses (75–300 mg) it is used for cardiovascular prevention. At high doses (500–1000 mg) it acts as an analgesic and antipyretic. In Spain it is available without a prescription at analgesic doses, but antiplatelet doses require a prescription.
Irreversible inhibition of platelet COX
Aspirin has a unique mechanism that sets it apart from all other NSAIDs:
- It acetylates platelet COX-1 IRREVERSIBLY → it blocks thromboxane A2 (TXA2) production for the whole life of the platelet.
- Platelets have no nucleus: they cannot make new COX. The effect lasts the platelet's whole life (7–10 days).
- At low doses (75–100 mg): mainly an antiplatelet effect, with minimal gastric effect.
- At high doses (>500 mg): it also inhibits COX-2 → analgesic, antipyretic and anti-inflammatory effect.
- Paradoxical effect at very high doses: it can inhibit endothelial prostacyclin (a vasodilator) and lose part of the antiplatelet effect.
At the counter
When to recommend it
- Secondary cardiovascular prevention (after a heart attack, after an ischaemic stroke, stable angina): low doses (75–100 mg a day)
- Suspected heart attack: a chewed loading dose when the emergency service instructs it
- Pain relief and fever in adults (500–1000 mg): headache, dental pain, fever
- Remind the patient to take the daily antiplatelet dose even when they 'feel fine': it is preventive, not for symptoms
When not to
- Children and adolescents under 16 with a viral fever: risk of Reye's syndrome (serious hepatic encephalopathy)
- Pregnancy: contraindicated in the third trimester (like all NSAIDs)
- Allergy to NSAIDs or aspirin-induced asthma
- Haemophilia or other clotting disorders
- Active peptic ulcer without gastric protection
- Combination with anticoagulants without a specific medical indication
Warnings
- Important REYE'S SYNDROME: aspirin in under-16s with viral febrile illnesses (flu, chickenpox) can cause Reye's syndrome: encephalopathy and acute liver failure, potentially fatal. Absolutely contraindicated in this group.
- Important BLEEDING: the antiplatelet effect is irreversible and lasts 7–10 days. If the patient is going to have surgery or a tooth extraction, whether to stop it is their doctor's decision: in secondary prevention it is often NOT stopped, because stopping it carries risk too. Never stop it on their own initiative.
- Caution INTERACTION WITH IBUPROFEN: ibuprofen taken before aspirin can block the acetylation site on COX and cancel the antiplatelet effect. If both are needed, take the aspirin at least 30 minutes before the ibuprofen.
- Caution ANTICOAGULANTS: aspirin + an anticoagulant (warfarin, acenocoumarol, direct oral anticoagulants) multiplies the risk of bleeding. It is only done on an explicit medical indication.
- Worth knowing VARIABLE RESPONSE: some patients respond less well to aspirin (so-called 'resistance', a concept still debated). In any case, the most frequent reason behind a treatment failure is not taking it.
Pharmacokinetics
- Absorption
- Oral: rapid and almost complete absorption. Peak plasma level at 30–40 minutes. Effervescent forms act faster. Gastro-resistant tablets are absorbed more slowly but cause less gastric irritation.
- Distribution
- High plasma protein binding (80–90%). Wide distribution. It crosses the placenta and passes into breast milk.
- Metabolism
- Hepatic: it is hydrolysed to salicylic acid (an active metabolite) and then to several metabolites. Metabolism is saturable at high doses: at antiplatelet doses the kinetics are first-order; at high doses they can become zero-order.
- Elimination
- Renal, dependent on urine pH. Half-life: 15–20 minutes (aspirin) / 2–3 hours (salicylate) at low doses; 15–30 hours at high doses. Alkalinising the urine speeds up elimination (useful in poisoning).
Antiplatelet aspirin vs clopidogrel
| Aspect | Antiplatelet aspirin | Clopidogrel |
|---|---|---|
| Mechanism | Inhibits TXA2 (via COX-1) | Blocks the ADP P2Y12 receptor |
| Onset of action | 30–60 min (loading dose: chewed) | 2–6 hours |
| Duration of effect | Platelet lifespan (7–10 days) | Platelet lifespan (7–10 days) |
| Gastric risk | Moderate (gastro-resistant forms) | Lower |
| Main indication | Secondary prevention (in primary prevention, only selected cases) | After a stent, acute coronary syndrome |
| Dual antiplatelet therapy | Aspirin + clopidogrel in the acute phase after a stent | For 6–12 months after a stent |
Aspirin is the baseline antiplatelet for most cardiovascular patients. Clopidogrel is added or substituted in specific situations. Dual antiplatelet therapy increases the risk of bleeding and needs monitoring.
Self-assessment
Three questions. When you check your answers you will see the explanation for each one.
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Reye's syndrome is a serious and potentially fatal hepatic encephalopathy associated with aspirin use in under-16s during viral febrile illnesses. It is absolutely contraindicated. Paracetamol is the safe alternative (in chickenpox, ibuprofen is not an option either).
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Ibuprofen can block the acetylation site on platelet COX and prevent aspirin from exerting its antiplatelet effect. If both are taken, the aspirin should be taken at least 30 minutes before the ibuprofen. The safest alternative is paracetamol, which does not have this interaction.
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Aspirin irreversibly acetylates platelet COX-1. Having no nucleus, platelets cannot make new COX to replace the blocked enzyme. The effect lasts the platelet's whole life (7–10 days), far longer than the drug stays in the plasma.
Training content. It does not replace the summary of product characteristics or clinical judgement.