Antiplatelets: aspirin, clopidogrel & DAPT

Antiplatelets: aspirin, clopidogrel and DAPT

Antiplatelets reduce platelet activation and arterial thrombus formation. They are central to acute coronary syndrome (ACS), coronary stents and secondary prevention after atherothrombotic events, but they also increase bleeding. Safe decisions therefore depend on five questions: what is the indication, which agent is appropriate, is combination therapy needed, for how long, and what is the person's bleeding risk?

Quick answer: aspirin is usually continued indefinitely after myocardial infarction unless contraindicated. Dual antiplatelet therapy (DAPT) combines aspirin with a P2Y12 inhibitor after ACS or PCI, commonly for up to 12 months, but the exact regimen is individualised. Never stop DAPT after a recent coronary stent without specialist advice.

Platelets and arterial thrombosis

When an atherosclerotic plaque ruptures, platelets adhere, activate and aggregate. This platelet-rich clot can obstruct a coronary, cerebral or peripheral artery. Antiplatelets are therefore used mainly against arterial thrombosis. Anticoagulants target the coagulation cascade and are generally more important for fibrin-rich venous thrombosis and cardioembolic stroke, such as stroke prevention in atrial fibrillation.

This distinction prevents a common error: aspirin is not an adequate substitute for anticoagulation in atrial fibrillation.

The main antiplatelets

Drug	Main action	Practical points
Aspirin	Irreversibly inhibits platelet COX-1 and thromboxane A2 formation	Rapid, inexpensive and usually the long-term agent after MI. Dyspepsia, ulceration, bleeding and hypersensitivity are important harms.
Clopidogrel	Irreversibly blocks the platelet P2Y12 ADP receptor	A prodrug activated partly by CYP2C19. Used in DAPT and as single-agent secondary prevention in several vascular indications.
Ticagrelor	Direct, reversible P2Y12 inhibitor	More potent than clopidogrel in ACS settings. Can cause bleeding, dyspnoea and bradyarrhythmia; usually taken twice daily.
Prasugrel	Irreversible P2Y12 inhibitor; prodrug	Potent and used around PCI. Bleeding risk is important, particularly in older or low-weight patients; previous stroke or TIA is a major contraindication.
Dipyridamole	Inhibits platelet function and has vasodilator activity	Used in selected stroke/TIA secondary-prevention pathways when preferred agents are unsuitable. Headache is common.

Because aspirin, clopidogrel and prasugrel affect platelets for their lifespan, recovery after stopping is not immediate. Ticagrelor is reversible, but its clinical effect also persists after the last dose. Peri-procedural decisions must follow the proceduralist or cardiology plan rather than an improvised fixed interval.

Primary prevention is not secondary prevention

Primary prevention

Do not recommend routine aspirin simply because someone has cardiovascular risk factors. In people without established cardiovascular disease, the reduction in vascular events may be offset by major bleeding. Risk-factor management normally centres on smoking cessation, blood-pressure control, lipid modification, diabetes care, activity and diet.

Secondary prevention

Once someone has established atherothrombotic disease, the balance changes. Typical indications include:

• previous myocardial infarction or ACS;
• PCI with coronary stent insertion;
• previous non-cardioembolic ischaemic stroke;
• peripheral arterial disease; and
• multivascular disease.

The correct antiplatelet is not identical across all of these conditions. For example, NICE recommends clopidogrel as an option after ischaemic stroke and for peripheral arterial or multivascular disease. After MI, aspirin is generally continued indefinitely, with clopidogrel considered when aspirin is contraindicated or not tolerated.

DAPT after ACS and PCI

DAPT means aspirin plus a P2Y12 inhibitor. It reduces recurrent ischaemic events and stent thrombosis but causes more bleeding than one antiplatelet alone.

NICE's ACS pathway distinguishes the clinical setting:

• STEMI treated with primary PCI: prasugrel with aspirin is normally offered when the person is not already taking oral anticoagulation. In people aged 75 or over, bleeding risk may favour ticagrelor or clopidogrel. If ongoing anticoagulation is already required, clopidogrel is the usual P2Y12 partner.
• Unstable angina or NSTEMI proceeding to angiography/PCI: prasugrel or ticagrelor with aspirin may be used when there is no separate anticoagulation indication. Prasugrel is given only after coronary anatomy is known and PCI is intended. Clopidogrel is used when ongoing anticoagulation is required.
• Unstable angina or NSTEMI managed without PCI: ticagrelor with aspirin is normally offered unless bleeding risk is high; clopidogrel with aspirin or aspirin alone may be considered when bleeding risk is high.

DAPT is commonly continued for up to 12 months after MI, unless contraindicated. However, duration is not a number to apply blindly. The cardiology plan may shorten therapy for high bleeding risk or extend antiplatelet therapy in selected people with high ischaemic risk. Always verify the discharge letter, PCI report and intended stop date.

Why adherence after a stent matters

A coronary stent is thrombogenic until endothelial healing occurs. Premature antiplatelet interruption can cause acute stent thrombosis, myocardial infarction or death. If a patient with a recent stent reports bruising, dental work or planned surgery, do not simply advise them to stop treatment. Establish:

1. the date and reason for PCI;
2. the stent and ACS history if available;
3. the prescribed DAPT duration;
4. which clinician is coordinating the procedure; and
5. whether bleeding is minor, clinically relevant or an emergency.

Urgent active bleeding requires immediate clinical assessment. Elective interruption requires agreement between the procedural team and the clinician responsible for the antiplatelet plan.

Antiplatelets plus anticoagulation

Combining an anticoagulant with one or two antiplatelets sharply increases bleeding. Long-term triple therapy—an anticoagulant, aspirin and a P2Y12 inhibitor—is therefore avoided where possible.

After ACS or PCI in someone who also needs anticoagulation, the regimen and duration are specialist decisions based on thromboembolic, ischaemic and bleeding risks. NICE advises anticoagulation plus clopidogrel for up to 12 months after PCI in relevant patients and warns that long-term triple therapy significantly increases bleeding. Do not add aspirin to an anticoagulant for vague “extra protection”.

Bleeding-risk assessment

Before starting or reviewing treatment, ask about:

• previous GI ulcer, GI bleeding or intracranial haemorrhage;
• unexplained anaemia, melaena, haematemesis, haematuria or prolonged bleeding;
• age, frailty, falls and alcohol intake;
• renal or hepatic impairment;
• planned surgery, invasive procedures or dental treatment; and
• other medicines that increase bleeding.

Important interacting groups include anticoagulants, NSAIDs, corticosteroids and SSRIs/SNRIs. The combination may still be clinically necessary, but it should trigger a clear indication check, gastroprotection assessment, counselling and monitoring plan.

Gastroprotection and the clopidogrel–PPI interaction

A PPI should be considered when GI risk is increased—for example older age, previous ulcer or GI bleed, Helicobacter pylori, or concomitant medicines that raise bleeding risk.

Clopidogrel requires CYP2C19 for conversion to its active metabolite. Omeprazole and esomeprazole inhibit CYP2C19 and should generally be avoided with clopidogrel. If a PPI is required, NHS Specialist Pharmacy Service recommends lansoprazole, pantoprazole or rabeprazole in preference.

Separating omeprazole and clopidogrel by several hours does not reliably solve the interaction. Also ask about over-the-counter omeprazole because it may not appear on the repeat list.

Adverse effects and counselling

Explain the purpose first: the medicine prevents a serious clot even though the benefit is not something the patient can feel day to day.

Counselling should include:

• take the medicine consistently and do not stop it without advice;
• minor bruising or slightly prolonged bleeding can occur;
• seek urgent help for vomiting blood, black tarry stools, coughing blood, severe or persistent headache after a head injury, sudden neurological symptoms, or bleeding that will not stop;
• check before using ibuprofen, naproxen or aspirin-containing over-the-counter products;
• tell clinicians, dentists and pharmacists about all antiplatelets and anticoagulants; and
• for ticagrelor, mention that breathlessness can occur, but new or severe breathlessness still needs assessment rather than automatic attribution to the drug.

There is no routine laboratory test used to titrate aspirin or clopidogrel in ordinary practice. Review focuses on indication, intended duration, adherence, adverse effects, interacting medicines and relevant full blood count or organ-function results when clinically indicated.

A structured OSCE approach

1. Confirm the indication

Ask what happened—MI, stroke, PAD or PCI—and when. Identify whether the patient is in the acute DAPT phase or on long-term single therapy.

2. Reconcile every antithrombotic

List aspirin, P2Y12 inhibitors and all anticoagulants. Confirm doses and the intended stop date rather than assuming duplicate therapy is accidental.

3. Screen for harm

Ask directly about bleeding, dyspepsia, adherence, falls, recent head injury and planned procedures. Check haemoglobin, platelets, renal function and liver function if the scenario provides them.

4. Check interactions

Look specifically for NSAIDs, anticoagulants, SSRIs/SNRIs, corticosteroids and omeprazole/esomeprazole with clopidogrel.

5. Make a safe plan

Preserve essential antithrombotic protection, address modifiable bleeding risks, add or optimise gastroprotection when indicated, document duration and escalate uncertainty to cardiology or the responsible specialist.

Common mistakes

• Recommending aspirin for routine primary prevention.
• Treating all vascular indications as if they use the same antiplatelet.
• Starting DAPT for undifferentiated chest pain before ACS is diagnosed.
• Stopping DAPT after recent PCI without specialist agreement.
• Missing an anticoagulant and unintentionally creating prolonged triple therapy.
• Pairing clopidogrel with omeprazole or esomeprazole without reviewing alternatives.
• Reassuring severe headache after a fall as “just bruising”.

Active recall

1. Why is aspirin generally unsuitable for routine primary prevention?
2. What does DAPT mean, and what competing risks determine its duration?
3. Which PPI interaction should you actively check in a patient taking clopidogrel?
4. Why must antiplatelets after a recent coronary stent not be stopped casually?
5. Which additional medicine turns DAPT into triple antithrombotic therapy?

Authoritative sources

• NICE NG185: Acute coronary syndromes
• NICE TA210: Clopidogrel and modified-release dipyridamole
• NHS SPS: Using clopidogrel with proton pump inhibitors
• MHRA: Clopidogrel and PPIs—updated interaction advice

Educational material for UK pharmacy learners. Apply the current BNF, local antithrombotic policy and the patient's specialist plan in practice.