What medication inhibits adenosine diphosphate (ADP)-induced platelet aggregation?

Adenosine Diphosphate-Induced Platelet Aggregation Inhibition

Clopidogrel is the medication that inhibits adenosine diphosphate (ADP)-induced platelet aggregation. 1, 2

Mechanism of Action of Different Antiplatelet Agents

Clopidogrel

• Clopidogrel irreversibly binds its active metabolite to the P2Y12 ADP receptor on platelets, thereby inhibiting ADP-induced platelet activation and aggregation 2
• The active metabolite of clopidogrel prevents the signaling cascade normally triggered by ADP binding to P2Y12, including:
  • Inhibition of adenylate cyclase
  • Decrease of cAMP levels
  • Prevention of platelet aggregation 1, 2
• This binding is covalent and irreversible, affecting platelets for their entire lifespan (7-10 days) 2

Aspirin

• Aspirin (acetylsalicylic acid) works by inhibiting cyclooxygenase-1 (COX-1) and blocking the formation of thromboxane A2 1
• This inhibits platelet aggregation induced via the thromboxane pathway, not the ADP pathway 1
• Aspirin has no direct effect on ADP-induced platelet aggregation 1

Heparin

• Heparin is an anticoagulant that works by binding to antithrombin III and enhancing its activity
• It has no direct effect on platelet aggregation or the ADP pathway
• It primarily affects the coagulation cascade rather than platelet function

Dipyridamole

• Dipyridamole inhibits the uptake of adenosine into platelets, endothelial cells, and erythrocytes 3
• It increases local concentrations of adenosine which stimulates platelet adenylate cyclase and increases platelet cAMP levels 3
• While dipyridamole can indirectly affect platelet function, it does not directly inhibit ADP-induced platelet aggregation 4, 5
• Dipyridamole's effect on ADP-induced aggregation is weak and requires high doses 6

Coumadin (Warfarin)

• Warfarin inhibits vitamin K-dependent coagulation factors (II, VII, IX, and X) and proteins C, S, and Z 1
• It has no direct effect on platelet function or ADP-induced platelet aggregation

Clinical Relevance

The inhibition of ADP-induced platelet aggregation by clopidogrel is particularly important in:

• Patients with coronary artery disease
• Those undergoing percutaneous coronary intervention
• Patients with acute coronary syndromes
• Prevention of thrombotic events in patients with moderate to severe coronary artery aneurysms 1

Clopidogrel is often used in combination with aspirin (dual antiplatelet therapy) to provide more comprehensive platelet inhibition through different pathways 1.

Monitoring and Response

• With daily 75 mg dosing of clopidogrel, 25-30% inhibition of platelet aggregation occurs from the second day of treatment, reaching steady state between days 3-7 2
• Maximum inhibition at steady state is 50-60% 2
• 5-10% of patients are completely resistant to clopidogrel's effects, and up to 25% show only partial responsiveness 2

Therefore, based on the evidence presented, the answer is (c) clopidogrel (which belongs to the same class as dipyridamole but directly inhibits the P2Y12 ADP receptor).