Why is aspirin (acetylsalicylic acid) recommended for patients with coronary artery disease?

Why Aspirin is Recommended for Coronary Artery Disease

Aspirin is recommended for patients with coronary artery disease because it irreversibly inhibits platelet cyclooxygenase-1, blocking thromboxane A2 production and reducing the risk of coronary thrombosis, thereby decreasing death and major adverse cardiovascular events by approximately 20-25%. 1

Mechanism of Action and Clinical Benefit

Aspirin works by irreversibly acetylating platelet cyclooxygenase-1, which prevents the formation of thromboxane A2—a potent platelet aggregator and vasoconstrictor. 2 This antiplatelet effect is critical because:

• Platelets play a central role in atherothrombotic coronary events, forming the initial thrombus at sites of plaque rupture or erosion 3
• Aspirin reduces serious vascular events (myocardial infarction, stroke, or cardiovascular death) by approximately 20-25% across a broad range of high-risk patients with established coronary disease 1, 2
• The absolute benefit substantially outweighs bleeding risks in patients with established coronary artery disease 1, 4

Evidence-Based Indications in Coronary Artery Disease

Acute Coronary Syndromes

For patients presenting with acute coronary syndromes, aspirin should be administered immediately with a loading dose of 162-325 mg, followed by daily low-dose maintenance therapy (75-100 mg). 1

• Aspirin reduces vascular death by 23% and non-fatal vascular events by 50% when started within 24 hours of acute myocardial infarction 1
• The loading dose ensures rapid and complete inhibition of thromboxane A2-dependent platelet aggregation, which is critical during the acute thrombotic phase 1, 5
• Aspirin must be combined with a P2Y12 inhibitor (clopidogrel, ticagrelor, or prasugrel) as dual antiplatelet therapy during the first year after acute coronary syndrome to reduce major adverse cardiovascular events and stent thrombosis 1

Chronic Coronary Disease (Stable CAD)

For patients with established coronary artery disease—including those >1 year post-acute coronary syndrome, with prior revascularization, coronary stenoses >50% on angiography, or evidence of cardiac ischemia—long-term single antiplatelet therapy with aspirin 75-100 mg daily is recommended. 1, 4

• Low-dose aspirin (75-100 mg daily) decreases infarction and sudden death by more than 30% in patients with stable angina 5
• The absolute risk reduction is 36 per 1,000 patients treated for 2 years among those with previous myocardial infarction 1
• This dose exceeds the minimal effective dose for complete thromboxane A2 suppression while minimizing gastrointestinal toxicity 1

After Percutaneous Coronary Intervention

Aspirin is mandatory during and after PCI with stent placement to prevent stent thrombosis, which can be catastrophic. 1

• Aspirin combined with a P2Y12 inhibitor reduces stent thrombosis risk during the critical period after stent implantation 1
• For bare-metal stents, dual antiplatelet therapy is recommended for at least 1 month; for drug-eluting stents, 3-6 months minimum, with continuation to 12 months suggested 1
• After completing dual antiplatelet therapy, aspirin monotherapy (75-100 mg daily) should be continued lifelong 4, 6

Optimal Dosing Strategy

The evidence supports a two-phase dosing approach:

Acute Phase (ACS or PCI):

• Loading dose: 162-325 mg to achieve rapid platelet inhibition 1, 5
• This higher initial dose ensures complete and immediate blockade during acute thrombotic events 5

Chronic Maintenance Phase:

• Daily dose: 75-100 mg for long-term secondary prevention 1, 4
• Doses below 100 mg are as effective as higher doses while causing significantly fewer gastrointestinal adverse effects 1, 5
• The most common low-dose tablet in the US is 81 mg 4

Critical Caveats and Common Pitfalls

When to Use Dual Antiplatelet Therapy vs. Aspirin Alone

A common error is continuing dual antiplatelet therapy indefinitely or stopping it too early. The evidence-based approach is:

• First 12 months after ACS or PCI with stent: Dual antiplatelet therapy (aspirin + P2Y12 inhibitor) 1
• After 12 months in stable patients: Transition to aspirin monotherapy unless specific high-risk features warrant continuation 1, 4
• Exception: Patients on oral anticoagulation should discontinue aspirin after 1-4 weeks post-PCI while maintaining P2Y12 inhibitor plus anticoagulant to reduce bleeding risk 1

Aspirin Intolerance or Allergy

For patients with true aspirin allergy not amenable to desensitization, clopidogrel 75 mg daily is the recommended alternative. 4, 6

• Aspirin desensitization is preferred whenever possible to allow initial dual antiplatelet therapy 1
• P2Y12 inhibitors alone are less effective than aspirin for long-term secondary prevention in most patients 1

Bleeding Risk Management

While aspirin increases major gastrointestinal bleeding risk (relative risk 1.6), the absolute increase is small (2-4 per 1,000 middle-aged adults over 5 years) and is far outweighed by cardiovascular benefits in patients with established coronary disease. 4, 6

• Routine proton pump inhibitor use is not recommended for patients taking low-dose aspirin (75-100 mg) due to lack of evidence supporting this strategy 1
• Proton pump inhibitors should be reserved for patients at higher than average risk of gastrointestinal bleeding 7
• Absolute contraindications include: active gastrointestinal bleeding, severe thrombocytopenia, or hemophilia 6

Drug Interactions

Traditional NSAIDs (particularly ibuprofen) can interfere with aspirin's antiplatelet effect through competitive inhibition of the cyclooxygenase-1 binding site. 1

• Patients requiring NSAID therapy while on aspirin may benefit from selective COX-2 inhibitors to avoid this interaction 1
• NSAIDs should not be used routinely in patients with coronary disease due to increased cardiovascular risk 1

Why Not Higher Doses?

Higher aspirin doses (>100 mg daily) do not provide additional cardiovascular benefit but significantly increase bleeding complications. 1, 5

• The antiplatelet effect plateaus at doses of 75-100 mg because this completely suppresses thromboxane A2 production 1
• Gastrointestinal toxicity increases substantially with doses above 100 mg, reducing compliance 1, 5
• The evidence consistently supports 75-100 mg as the optimal balance of efficacy and safety for chronic therapy 1, 4