In the arteries (fast flowing vessels), blood clots (thrombi) are composed mainly of platelets with little fibrin. Antiplatelet treatment decreases platelet aggregation and inhibits thrombosis formation in the arteries. Many factors can cause damage to the vascular endothelium contributing to the formation of atherosclerotic plaques, such as smoking, diabetes and raised LDL-cholesterol levels. If plaques are disrupted, platelets aggregate and form thrombi which can lead to narrowing or occlusion of the vessel. Antiplatelet agents are indicated in cardiovascular disease, including myocardial infarction (MI), unstable and stable angina, peripheral arterial disease, stroke and transient ischaemic attack (TIA). Antiplatelet agents can also be used in atrial fibrillation and patients undergoing cardiac interventions such as stenting and angiography. Often aspirin is combined with a ADP/P2Y12 inhibitor to obtain greater effectiveness and this is known as dual antiplatelet therapy (DAPT). DAPT is indicated for the first year after a MI in the UK. This article will outline the different antiplatelets used in practice, their mechanism of action, cautions and contraindications of their use, side effects and any clinically significant drug interactions. By TeachMeSeries Ltd (2026)Fig 1: Different types of antiplatelets and their mechanism of action Aspirin Aspirin (acetylsalicylic acid) irreversibly blocks cyclo-oxygenase (COX) through acetylation, and therefore inhibits the production of thromboxane A2 (TxA2). Thromboxane is a powerful vasoconstrictor that lowers cyclic AMP (cAMP) and initiates the platelet release reaction. Aspirin has many cautions for its use. It is available as an enteric-coated tablet, which protects the stomach, as aspirin increases the risk of dyspepsia and rarely causes gastrointestinal haemorrhage. Aspirin is not recommended for use in children under 16 years of age unless the benefits outweigh risks, as it can cause Reye’s syndrome. Aspirin may promote bronchospasm and asthma attacks and should be used with caution in patients with asthma. This effect is due to inhibition of the COX enzymes; other antiplatelets do not have this effect. At low doses, aspirin reduces uric acid excretion, which can increase chance of gout attacks. By TeachMeSeries Ltd (2026) Fig 2: Mechanism of actionAspirin Clopidogrel and prasugrel Clopidogrel and prasugrel are thienopyridines. They irreversibly inhibit the binding of adenosine diphosphate (ADP) to its platelet P2Y12 receptor, blocking platelet activation and aggregation via activation of the IIb/IIIa complex. Platelets exposed to these drugs are affected for the remainder of their lifespan (approximately 7-10 days), and recovery of normal platelet function occurs at a rate consistent with platelet turnover. For this reason, clopidogrel is often discontinued 7 days prior to elective surgery where bleeding risk outweighs the risk of pausing therapy. Cross sensitivity among thienopyridines has been reported; therefore, monitoring for signs of hypersensitivity in patients with a known allergy to this class is advised. Clopidogrel is metabolised by CYP2C19 and is a prodrug. Use of strong inducers of CYP2C19 such as rifampicin with clopidogrel should be discouraged as this may potentiate the risk of bleeding. Use of strong or moderate CYP2C19 inhibitors (e.g. omeprazole, esomeprazole, fluoxetine, voriconazole, fluconazole and carbamazepine) with clopidogrel may result in reduced drug levels of the active metabolite and is therefore discouraged. Omeprazole is often indicated for patients who take clopidogrel when gastro-protection is indicated, especially if on DAPT, therefore it is common practice to switch to an alternative PPI, such as lansoprazole, to avoid the interaction. Prasugrel is also a prodrug and is metabolised primarily by CYP3A4 and CYP2B6, however inhibitors and inducers of CYP enzymes are not anticipated to have a significant effect on the pharmacokinetics of its active metabolite. Ticagrelor Ticagrelor is an adenosine triphosphate (ATP) analogue which reversibly blocks the P2Y12 receptor and prevents ADP-mediated P2Y12 dependent platelet activation and aggregation. Ticagrelor and its active metabolite (AR-C124910XX) are both active at the site of action. Ticagrelor may cause a rise in creatinine levels via an unknown mechanism; creatinine should be checked 1 month after treatment commences. Ticagrelor may also increase uric acid levels, therefore caution is advised if patients have a history of hyperuricaemia Ticagrelor also have several clinically significant interactions due to being a CYP3A4 substrate: Co-administration of ticagrelor with strong CYP3A4 inhibitors (e.g. ketoconazole & clarithromycin) is contraindicated, as this may substantially increase exposure to ticagrelor Co-administration of ticagrelor with potent CYP3A4 inducers (e.g. rifampicin) reduces ticagrelor levels; concomitant use is discouraged. Dipyridamole and cilostazol Dipyridamole and cilostazol are phosphodiesterase (PDE) III inhibitors which have antiplatelet and vasodilatory effects. They inhibit the uptake of adenosine, leading to a higher concentration of adenosine available to act on platelet A2 receptors. This increases platelet cAMP levels and inhibits platelet aggregation. Adenosine is also a vasodilator, contributing to the vasodilatory effect. Due to these vasodilatory effects, when dipyridamole is used with blood pressure-lowering drugs, it may increase hypotensive effects, so blood pressure should be monitored. Cilostazol is indicated in intermittent claudication. It is contraindicated in patients with unstable angina or MI/coronary intervention within the last 6 months. Cilostazol is extensively metabolised by CYP3A4 and CYP2C19. Patients taking strong inhibitors of CYP3A4 (e.g. erythromycin, clarithromycin, ketoconazole, itraconazole) or CYP2C19 (e.g. omeprazole) should take half the dose of cilostazol (reduce usual dose of 100mg twice daily to 50mg twice daily). Glycoprotein IIb/IIIa inhibitors Glycoprotein IIb/IIIa inhibitors (e.g. abciximab, eptifibatide, tirofiban) block the binding of fibrinogen to glycoprotein IIb/IIIa receptors on the platelet, thereby inhibiting aggregation. These drugs are administered intravenously to high-risk patients undergoing percutaneous coronary interventions or to people with acute coronary syndrome to prevent MI. General cautions for use of antiplatelets Cautions for use of antiplatelets are generally related to the increased risk of bleeding. The risk of bleeding should always be weighed against the benefit of treatment, particularly in patients with bleeding disorders or history of. or active, peptic ulcer. Caution should be taken with drug interactions described above that could increase antiplatelet levels, as well as other medications that can increase risk ulceration (e.g. oral corticosteroids, SSRIs) Furthermore, caution is advised when antiplatelets are used with anticoagulants, due to additive bleeding risk. Summary table The following table summarises the antiplatelets drugs discussed in this article: Drug/Class Mechanism of Action Key Indications Cautions/Contraindications Notable Side Effects Important Interactions Aspirin Irreversible COX inhibition → ↓ thromboxane A2 MI, stroke, angina, TIA, peripheral arterial disease Children <16 (Reye’s syndrome), asthma, peptic ulcer, gout Dyspepsia, GI bleed, bronchospasm, gout flare ↑ risk with SSRIs, corticosteroids, anticoagulants Clopidogrel (thienopyridine) Irreversible P2Y12 receptor blocker → ↓ platelet aggregation MI, stroke, PCI, angina, PAD Allergy to thienopyridines; stop 7 days before surgery Bleeding, rash Interactions with CYP2C19 inhibitors (omeprazole, fluoxetine, etc.); inducers (rifampicin) Prasugrel (thienopyridine) Irreversible P2Y12 receptor blocker (prodrug) PCI, ACS History of stroke/TIA; caution in bleeding risk Bleeding Fewer significant CYP interactions than clopidogrel Ticagrelor Reversible P2Y12 receptor blocker (ATP analogue) ACS, PCI History of intracranial bleed, severe liver disease, hyperuricaemia Dyspnoea, ↑ uric acid, ↑ creatinine Strong CYP3A4 inhibitors (contraindicated), CYP3A4 inducers ↓ effect Dipyridamole PDE III inhibitor → ↑ cAMP & adenosine → antiplatelet + vasodilation Stroke/TIA prevention (often with aspirin) Hypotension, caution with antihypertensives Headache, flushing, dizziness ↑ hypotensive effect with BP-lowering drugs Cilostazol PDE III inhibitor → ↑ cAMP & vasodilation Intermittent claudication Unstable angina, MI or PCI within 6 months Headache, palpitations Dose reduction with CYP3A4/2C19 inhibitors (e.g. erythromycin, omeprazole) Glycoprotein IIb/IIIa inhibitors (abciximab, eptifibatide, tirofiban) Block IIb/IIIa receptor → prevent fibrinogen binding & aggregation High-risk PCI, ACS Active bleeding, severe uncontrolled hypertension Bleeding, thrombocytopenia Used IV in hospital settings only References Antiplatelet treatment | Health topics A to Z | CKS | NICE accessed 5/9/24 Using NSAIDs in asthma – SPS – Specialist Pharmacy Service – The first stop for professional medicines advice accessed 5/9/24 Aspirin 75mg Gastro-Resistant Tablets – Summary of Product Characteristics (SmPC) – (emc) (medicines.org.uk) accessed 5/9/24 Clopidogrel 75 mg film-coated tablets – Summary of Product Characteristics (SmPC) – (emc) (medicines.org.uk) accessed 5/9/24 Efient 10 mg film-coated tablets – Summary of Product Characteristics (SmPC) – (emc) (medicines.org.uk) accessed 5/9/24 Attia 200 mg Modified-Release Capsules, Hard – Summary of Product Characteristics (SmPC) – (emc) (medicines.org.uk) accessed 5/9/24 Cilostazol 100 mg tablets – Summary of Product Characteristics (SmPC) – (emc) (medicines.org.uk) accessed 5/9/24 Aggrastat 50 mcg/ml Solution for infusion – Summary of Product Characteristics (SmPC) – (emc) (medicines.org.uk) accessed 5/9/24 Do you think you’re ready? Take the quiz below Pro Feature - Quiz Antiplatelets Question 1 of 3 Submitting... Skip Next Rate question: You scored 0% Skipped: 0/3 More Questions Available Upgrade to TeachMePharmacy Pro Challenge yourself with over 2100 multiple-choice questions to reinforce learning Learn More Rate This Article