Which is stronger in preventing blood clots, aspirin (acetylsalicylic acid) 150 mg or clopidogrel 75 mg?

Antiplatelet Potency: Clopidogrel 75 mg vs Aspirin 150 mg

Clopidogrel 75 mg is more potent than aspirin 150 mg in preventing atherothrombotic events, with a 23.8% greater relative risk reduction in patients with peripheral arterial disease and an 8.7% overall superiority across vascular disease populations. 1, 2

Direct Comparative Evidence

The CAPRIE trial provides the definitive head-to-head comparison, enrolling 19,185 patients randomized to clopidogrel 75 mg daily versus aspirin 325 mg daily (higher than the 150 mg dose in question). 2

• Clopidogrel reduced the annual risk of ischemic stroke, myocardial infarction, or vascular death to 5.3% versus 5.8% with aspirin, representing an 8.7% relative risk reduction (p=0.043). 2
• In the peripheral arterial disease subgroup specifically, clopidogrel demonstrated a 23.8% greater reduction in recurrent ischemic events compared to aspirin. 1
• Among patients with prior cardiac surgery, clopidogrel reduced vascular death, MI, stroke, or rehospitalization by 31.2% compared to aspirin (p=0.0003). 3

Mechanistic Differences Explaining Potency

The superior potency stems from fundamentally different mechanisms of action. 4

• Clopidogrel irreversibly blocks the P2Y12 ADP receptor on platelets, providing more complete platelet inhibition than aspirin's COX-1 inhibition. 4
• Aspirin at 150 mg provides no additional efficacy over 75-100 mg doses—the dose-response curve plateaus at lower doses. 1, 5
• The Antithrombotic Trialists' Collaboration meta-analysis showed aspirin 75-150 mg daily achieved 32% proportional reduction in vascular events, while 160-325 mg achieved only 26%, demonstrating no benefit to higher aspirin doses. 1

Clinical Context and Bleeding Risk Trade-offs

Both agents increase bleeding risk, but clopidogrel's superior efficacy comes with modestly higher bleeding rates. 6

• In CAPRIE, gastrointestinal hemorrhage occurred significantly less often with clopidogrel (0.52%) than aspirin 325 mg (0.72%, p<0.05), though this comparison used higher-dose aspirin. 1, 2
• Major bleeding requiring ≥2 units transfusion occurred in 0.52% with clopidogrel versus 0.72% with aspirin in CAPRIE. 2
• The FDA label warns that clopidogrel "can cause bleeding which can be serious and can sometimes lead to death," with effects lasting 7-10 days after discontinuation. 6

Important Caveats

Clopidogrel's effectiveness is compromised in 5-10% of patients with genetic polymorphisms affecting CYP2C19 metabolism, and up to 25% show partial responsiveness. 4

• Proton pump inhibitors, particularly omeprazole and esomeprazole, significantly reduce clopidogrel's antiplatelet activity and should be avoided. 6
• Clopidogrel requires hepatic CYP450 conversion to its active metabolite, creating drug-drug interaction vulnerabilities that aspirin lacks. 4

Guideline-Based Recommendations

Current guidelines position clopidogrel as superior to aspirin for specific high-risk populations. 1

• The ACC/AHA guidelines give clopidogrel a Class I, Level A recommendation as an alternative to aspirin for lifelong antiplatelet therapy in coronary artery disease patients who cannot tolerate aspirin. 4
• For peripheral arterial disease, the 22% odds reduction in cardiovascular events with antiplatelet therapy was enhanced with clopidogrel over aspirin. 1
• In acute coronary syndromes, dual antiplatelet therapy (aspirin plus clopidogrel) is standard, but when monotherapy is required, clopidogrel demonstrates superior efficacy. 1