What are the inhibitors of platelet aggregation?

From the Guidelines

The most effective inhibitors of platelet aggregation are dual antiplatelet therapy (DAPT) combining aspirin with a P2Y12 inhibitor like ticagrelor, which has been shown to be more potent than clopidogrel in preventing platelet aggregation 1. The choice of antiplatelet agent depends on the clinical context, including the presence of acute coronary syndromes, percutaneous coronary interventions, or coronary stent placement.

• Aspirin (75-325 mg daily) is the most commonly used antiplatelet agent and works by irreversibly inhibiting cyclooxygenase-1.
• P2Y12 inhibitors, such as clopidogrel (75 mg daily), prasugrel (10 mg daily), and ticagrelor (90 mg twice daily), block ADP receptors on platelets and are often used in combination with aspirin.
• Glycoprotein IIb/IIIa inhibitors, such as tirofiban, eptifibatide, or abciximab, prevent the final common pathway of platelet aggregation and are typically used short-term in acute coronary syndromes or percutaneous coronary interventions. It is essential to consider the potential risks and benefits of each antiplatelet agent, including the increased risk of bleeding, and to monitor patients regularly for side effects such as bruising, bleeding gums, or gastrointestinal bleeding 1. In patients with coronary stent placement, the duration of DAPT varies from 1-12 months depending on stent type and bleeding risk, with ticagrelor being a preferred option due to its higher potency and efficacy in preventing platelet aggregation 1.

From the FDA Drug Label

The active thiol metabolite binds rapidly and irreversibly to platelet receptors, thus inhibiting platelet aggregation for the lifespan of the platelet. Clopidogrel is a prodrug and is metabolized to a pharmacologically active metabolite and inactive metabolites. P2Y12 inhibitors (thienopyridines), including clopidogrel, increase the risk of bleeding. P2Y12 inhibitors (thienopyridines), inhibit platelet aggregation for the lifetime of the platelet (7 to 10 days)

Inhibitors of platelet aggregation are medications that prevent platelets from clumping together to form blood clots.

• Clopidogrel is an example of a platelet aggregation inhibitor, which works by binding to platelet receptors and preventing them from aggregating.
• The active metabolite of clopidogrel is responsible for its antiplatelet effects, and its formation can be affected by genetic variations in the CYP2C19 gene.
• Concomitant use of certain medications, such as omeprazole or esomeprazole, can reduce the antiplatelet activity of clopidogrel by inhibiting the CYP2C19 enzyme 2.
• Bleeding risk is a potential side effect of platelet aggregation inhibitors, including clopidogrel, and can be increased by concomitant use of other medications that affect bleeding risk 2.

From the Research

Inhibitors of Platelet Aggregation

• The mainstay therapy in patients with acute coronary syndrome is dual antiplatelet therapy, which combines aspirin and a P2Y12 inhibitor to reduce the rate of stent thrombosis and major adverse cardiovascular events 3.
• Newer P2Y12 inhibitors, such as prasugrel and ticagrelor, have better efficacy than clopidogrel, with prasugrel providing greater inhibition of platelet aggregation and a rapid onset of action 3, 4.
• In patients with acute cerebrovascular disease, aspirin combined with clopidogrel reduces subsequent risk, while in acute coronary syndrome, dual antiplatelet therapy comprising aspirin and a P2Y12 inhibitor confers greater protection than aspirin monotherapy 4.
• A systematic review and meta-analysis of randomized trials found that prasugrel and ticagrelor were associated with similar cardiovascular outcomes and adverse bleeding events in patients with acute coronary syndrome undergoing percutaneous coronary intervention 5.
• Antiplatelet agents, such as aspirin and clopidogrel, play a fundamental role in the treatment and management of secondary thrombotic events, with aspirin reducing the risk of thrombotic events by approximately 25% and clopidogrel providing an additional 8.7% relative risk reduction in the primary composite endpoint of ischemic stroke, myocardial infraction or vascular death compared with aspirin 6.
• The choice of antiplatelet agent to add to aspirin in the treatment of patients with acute coronary syndromes depends on various factors, and a practical guide to clinicians for determining which antiplatelet to use is necessary 7.

Types of Inhibitors

• Aspirin: reduces the risk of thrombotic events by approximately 25% 6.
• Clopidogrel: provides an additional 8.7% relative risk reduction in the primary composite endpoint of ischemic stroke, myocardial infraction or vascular death compared with aspirin 6.
• Prasugrel: provides greater inhibition of platelet aggregation and a rapid onset of action 3, 4.
• Ticagrelor: has better efficacy than clopidogrel, with similar cardiovascular outcomes and adverse bleeding events as prasugrel 4, 5.

Clinical Applications

• Dual antiplatelet therapy is recommended for patients with acute coronary syndrome, with the combination of aspirin and a P2Y12 inhibitor reducing the rate of stent thrombosis and major adverse cardiovascular events 3, 4.
• Aspirin combined with clopidogrel is recommended for patients with acute cerebrovascular disease 4.
• The choice of antiplatelet agent depends on various factors, including the patient's medical history and the specific clinical scenario 7.