Antiplatelet Therapy with Aspirin and Clopidogrel

Mechanism of Action

Aspirin irreversibly inactivates cyclooxygenase (COX-1) enzyme, preventing formation of thromboxane A2, a potent vasoconstrictor and platelet aggregator, acting on the arachidonic acid pathway of platelet activation 1, 2
Clopidogrel irreversibly binds the platelet surface P2Y12 adenosine diphosphate (ADP) receptor, inhibiting ADP-induced platelet activation through a completely different pathway than aspirin 3, 4
Clopidogrel is a prodrug requiring metabolic activation 4

In the CAPRIE trial, clopidogrel 75 mg daily reduced the relative risk of MI, ischemic stroke, or vascular death by 8.7% compared to aspirin 325 mg daily in 19,185 high-risk patients (9.8% vs 10.6%, p=0.045) 5
The American College of Chest Physicians recommends clopidogrel as an alternative to aspirin for secondary prevention in patients with cerebrovascular disease, with a strength of evidence grade of 1B 5

The American Heart Association recommends adding clopidogrel to aspirin in patients with acute coronary syndrome, as it reduces cardiovascular death, MI, or stroke by 20% (9.3% vs 11.4%, p<0.001) over 9 months 5, 3
In the COMMIT trial, adding clopidogrel 75 mg to aspirin 162 mg reduced in-hospital death by 7% and death/MI/stroke by 9% in 45,852 patients with ST-elevation myocardial infarction 5, 3

The incidence of thrombocytopenia with clopidogrel is identical to aspirin 5, 6
The combination of aspirin and clopidogrel significantly increases bleeding risk compared to either agent alone, with a major bleeding rate of 3.7% compared to 2.7% with aspirin alone (p<0.001) 5, 7

Thrombotic thrombocytopenic purpura (TTP) can occur with clopidogrel, typically within the first 2 weeks of therapy, with an incidence of approximately 11 cases per 3 million patients treated 5, 6, 7
TTP requires urgent plasmapheresis when identified 6

Low-dose aspirin (75-100 mg daily) provides effective antithrombotic protection while minimizing gastrointestinal toxicity 7
The standard clopidogrel maintenance dose is 75 mg daily 5

The American College of Cardiology recommends that patients with stable cardiovascular disease without recent events should not receive DAPT due to increased bleeding without mortality benefit 8
DAPT should not be used for stroke prevention in atrial fibrillation when anticoagulation is appropriate, as warfarin has demonstrated clear superiority over clopidogrel plus aspirin 8