4 Antiplatelet Drugs

Purpose and uses

Antiplatelet drugs reduce platelet activation or aggregation. They are used mainly to prevent arterial clots in acute coronary syndrome (ACS), after coronary stent placement, and after selected ischemic strokes. They are not interchangeable with anticoagulants, which act on the blood-clotting cascade.

Aspirin and platelet pathways

Aspirin irreversibly inhibits platelet cyclooxygenase-1 (COX-1), reducing thromboxane A₂ production and platelet aggregation. Because platelets cannot make new COX-1, the antiplatelet effect lasts for the affected platelet’s lifespan.

Aspirin is commonly used for secondary prevention of cardiovascular events, but it should not be assumed appropriate for primary prevention in every patient. Important adverse effects include gastrointestinal irritation, ulceration, and bleeding; hypersensitivity reactions can also occur.

P2Y₁₂ inhibitors

P2Y₁₂ inhibitors block ADP-mediated platelet activation. Common oral agents are clopidogrel, prasugrel, and ticagrelor. Clopidogrel and prasugrel are prodrugs that irreversibly inhibit the P2Y₁₂ receptor, whereas ticagrelor directly and reversibly inhibits it.

Clopidogrel activation partly depends on CYP2C19. Omeprazole and esomeprazole can reduce its antiplatelet activity, and the FDA label advises avoiding that combination.

Dual therapy and treatment decisions

Dual antiplatelet therapy (DAPT) usually combines aspirin with an oral P2Y₁₂ inhibitor, commonly clopidogrel, prasugrel, or ticagrelor. It is used to reduce recurrent ischemic events and stent thrombosis, including after ACS and coronary stent placement.

For ACS patients who are not at high bleeding risk, 12 months is the default strategy in the 2025 U.S. guideline. Treatment duration and drug choice are individualized when bleeding risk or other clinical factors differ.

Stopping antiplatelet therapy, especially soon after stent placement, can increase the risk of stent thrombosis and serious ischemic events. Before changing or stopping aspirin and clopidogrel for a dental procedure, the patient should contact the prescribing clinician and dentist. Decisions depend on the procedure, its timing, and individual clotting and bleeding risks.

Important safety distinctions

Prasugrel is contraindicated in patients with a prior stroke or transient ischemic attack (TIA), and in patients with active pathological bleeding. It can cause serious bleeding and is generally not recommended for adults aged 75 years or older except in selected high-risk circumstances.

Ticagrelor-associated dyspnea is a recognized adverse effect, and bleeding is also an important risk. New or severe shortness of breath requires clinical assessment rather than automatic attribution to the medication.

Other antiplatelet agents

Aspirin plus extended-release dipyridamole is used to reduce recurrent stroke risk after selected ischemic strokes or TIAs. Headache and gastrointestinal symptoms are common adverse effects, and bleeding is also a risk.

Cilostazol can reduce symptoms of intermittent claudication in peripheral arterial disease. It is contraindicated in heart failure of any severity; potential adverse effects include headache, palpitations, and tachycardia.

Glycoprotein IIb/IIIa inhibitors, such as eptifibatide and tirofiban, are intravenous agents used in selected acute coronary or PCI settings. They block the final common pathway of platelet aggregation and can cause bleeding and thrombocytopenia.

Comparing major risks

Bleeding is a central risk across antiplatelet drugs. Key drug-specific distinctions include avoiding prasugrel in patients with a prior stroke or TIA, recognizing possible dyspnea with ticagrelor, and avoiding cilostazol in heart failure.

• Antiplatelet drug