What are Acetylsalicylic Acids (ASAs), or aspirin, used for in patients with a history of cardiovascular disease?

What are ASAs (Acetylsalicylic Acid/Aspirin)?

ASAs (Acetylsalicylic Acid, commonly known as aspirin) are antiplatelet medications that irreversibly inhibit cyclooxygenase-1 (COX-1) enzyme in platelets, preventing thromboxane A2 formation and thereby reducing platelet aggregation and thrombosis risk. 1

Primary Mechanism and Clinical Use

ASAs work by permanently blocking the COX-1 enzyme in the arachidonic acid cascade, which prevents platelet aggregation through the thromboxane pathway 1. This antiplatelet effect has made aspirin a cornerstone medication in cardiovascular disease management for over 50 years 2.

Established Indications in Cardiovascular Disease

Secondary Prevention (Strongest Evidence)

For patients with established atherosclerotic cardiovascular disease, aspirin 75-162 mg daily is definitively recommended as secondary prevention. 3 The FDA has approved aspirin specifically for:

• Reducing vascular mortality in patients with suspected myocardial infarction 3
• Decreasing risk of death and nonfatal MI in patients with known coronary disease 3
• Prevention after stroke or transient ischemic attack 3

The evidence is compelling: among high-risk patients with established disease, antiplatelet therapy decreases nonfatal MI by approximately one-third, nonfatal stroke by one-fourth, and vascular death by one-sixth 3. For every 1,000 patients treated, aspirin prevents 10-20 vascular events 3.

Acute Coronary Syndrome Management

In acute coronary syndrome, administer a loading dose of 162-325 mg immediately (chewed for faster absorption), followed by 75-100 mg daily maintenance. 4, 5 The earlier aspirin is given during acute MI, the greater the mortality benefit 2.

For ongoing management after acute coronary syndrome, dual antiplatelet therapy (aspirin plus a P2Y12 inhibitor like clopidogrel) is reasonable for one year and may provide benefits beyond this period 3.

Optimal Dosing Strategy

The recommended maintenance dose is 75-100 mg daily, as higher doses increase gastrointestinal bleeding without additional cardiovascular benefit. 4 Key dosing evidence:

• Doses from 75 mg to >1500 mg provide similar cardiovascular benefits in secondary prevention 4
• The ADAPTABLE trial showed no difference in cardiovascular events between 81 mg and 325 mg daily doses 4
• Doses >100 mg increase GI bleeding risk proportionally without enhanced efficacy 4
• In the U.S., the most common low-dose tablet is 81 mg 3

Primary Prevention (Limited Role)

Aspirin is NOT routinely recommended for primary prevention due to bleeding risk exceeding cardiovascular benefit in most populations. 6 Recent high-quality evidence has fundamentally changed recommendations:

• The ARRIVE trial (12,546 patients) showed no cardiovascular benefit but doubled GI bleeding risk 6
• The ASPREE trial (19,114 elderly patients) demonstrated no cardiovascular benefit but 38% increased major hemorrhage 6
• The European Society of Cardiology states aspirin cannot be recommended for primary prevention even in individuals with multiple risk factors 6

Narrow Exception for High-Risk Diabetes

Aspirin 75-162 mg daily may be considered (not routinely recommended) only in highly selected diabetic patients who meet ALL criteria: 3, 6

• Age ≥50 years with type 1 or type 2 diabetes
• At least one additional major cardiovascular risk factor (family history of premature ASCVD, hypertension, dyslipidemia, smoking, or albuminuria)
• 10-year ASCVD risk ≥10%
• NOT at increased bleeding risk

Aspirin is contraindicated in patients <21 years due to Reye syndrome risk. 3

Critical Bleeding Risk Considerations

The major adverse effect is gastrointestinal bleeding, occurring at approximately 5 per 1,000 patients per year 3, 4, 5. Bleeding risk substantially increases with:

• Age >70 years 6
• Doses >100 mg daily 4
• Uncontrolled hypertension 5
• Concurrent anticoagulation or NSAIDs 5
• History of GI bleeding or ulcers 4

The European Society of Cardiology specifically recommends against aspirin in patients >70 years for primary prevention, as bleeding risk exceeds cardiovascular benefit. 6

Aspirin Allergy Management

For patients with documented aspirin allergy who require antiplatelet therapy, substitute clopidogrel 75 mg daily. 3, 4, 6 Alternatively, a rapid desensitization protocol under medical supervision may be considered, starting with 40.5 mg and increasing to 81 mg after 90 minutes 5.

Common Pitfalls to Avoid

• Do not prescribe aspirin for primary prevention in elderly patients (>70 years) - bleeding risk is prohibitive 6
• Do not use aspirin for primary prevention in patients with uncontrolled hypertension - hemorrhagic stroke risk increases markedly 6
• Do not combine aspirin with anticoagulation for primary prevention - bleeding risk becomes unacceptable 6
• Do not use enteric-coated aspirin for acute loading doses - chewable non-enteric formulations provide faster antiplatelet effect 5
• Do not assume traditional cardiovascular risk factors predict acute ischemic events - symptoms, ECG findings, and cardiac biomarkers are far more important for acute presentations 3

Additional Potential Benefits

Beyond cardiovascular protection, observational data suggest aspirin may reduce risk of esophageal, gastric, and colorectal cancer with regular use, though these effects are not uniform across all cancer types 3. However, cardiovascular indications remain the primary evidence-based use.