Is aspirin (acetylsalicylic acid) recommended for primary prevention of cardiovascular disease?

Aspirin for Primary Prevention of Cardiovascular Disease

Aspirin is generally NOT recommended for routine primary prevention of cardiovascular disease in most adults, as recent evidence demonstrates that bleeding risks equal or exceed cardiovascular benefits in contemporary populations receiving modern preventive therapies.

General Population Without Diabetes

Low-dose aspirin (75-100 mg daily) should NOT be routinely prescribed for primary prevention in the general population. 1

Key Evidence:

• The 2019 ACC/AHA guidelines downgraded aspirin to a Class IIb recommendation (may be considered, not routinely recommended) for adults aged 40-70 years at higher ASCVD risk but without increased bleeding risk 1
• Recent meta-analyses show aspirin reduces nonfatal MI by 21% but provides no reduction in cardiovascular death and increases major bleeding by 48% 2
• The number of cardiovascular events prevented equals the number of bleeding episodes induced in patients with ASCVD risk >1% per year 1

Absolute Contraindications (Do NOT Prescribe):

• Age >70 years - harm exceeds benefit for primary prevention 1, 3
• History of gastrointestinal bleeding or peptic ulcer disease 1, 3
• Concurrent anticoagulation (warfarin, DOACs) 1, 3
• Thrombocytopenia or coagulopathy 1, 3
• Chronic kidney disease 1, 3
• Uncontrolled hypertension 3
• Concurrent NSAID or steroid use 1, 3
• Age <21 years (Reye syndrome risk) 1

Patients With Diabetes

Aspirin may be considered (not routinely recommended) for select diabetic patients aged ≥50 years with additional cardiovascular risk factors and low bleeding risk, but only after comprehensive shared decision-making. 1

Selection Criteria for Consideration:

• Age ≥50 years with diabetes AND at least one additional major risk factor: 1
  • Family history of premature ASCVD
  • Hypertension
  • Dyslipidemia
  • Smoking
  • CKD/albuminuria
• AND no increased bleeding risk 1

Evidence in Diabetes:

• The ASCEND trial showed a 12% reduction in serious vascular events (8.5% vs 9.6%) but major bleeding increased from 3.2% to 4.1% (29% relative increase) 1
• Meta-analyses demonstrate no significant reduction in nonfatal MI or cardiovascular death in diabetic patients, with a 49% increase in bleeding risk 2
• For diabetic patients, aspirin had no effect on cardiovascular outcomes in recent trials 2, 4

Do NOT Prescribe in Diabetes:

• Age <50 years without other major risk factors 1
• Age >70 years (risk exceeds benefit) 1
• Any increased bleeding risk factors 1

Dosing When Aspirin Is Prescribed

Use 75-100 mg daily (81 mg in US) - the lowest effective dose to minimize bleeding risk. 1, 3

• Doses of 75-162 mg daily are acceptable 1, 3
• No evidence supports higher doses, and lower doses reduce side effects 1

Bleeding Risk Quantification

Major bleeding occurs in 2-4 per 1,000 middle-aged adults over 5 years (4-12 per 1,000 in older adults). 3

• Hemorrhagic stroke increases by 0-2 per 1,000 persons over 5 years 3
• Relative risk of major GI bleeding is 1.6 even with low doses 5
• Most excess bleeding is gastrointestinal and extracranial 1

Clinical Decision Algorithm

Step 1: Establish if Secondary Prevention

• YES → Aspirin 75-100 mg daily is strongly recommended 5, 3
• NO → Proceed to Step 2

Step 2: Screen for Absolute Contraindications

• Age >70 years? 1, 3
• History of GI bleeding? 1, 3
• On anticoagulation? 1, 3
• Uncontrolled hypertension? 3
• ANY YES → Do NOT prescribe aspirin

Step 3: Assess Cardiovascular Risk

• Low risk (age <50 without risk factors) → Do NOT prescribe 1
• Intermediate-High risk (age ≥50 with diabetes + ≥1 additional risk factor) → Proceed to Step 4 1

Step 4: Shared Decision-Making

• Discuss that bleeding risk equals or exceeds cardiovascular benefit 1, 2
• Consider coronary calcium scoring to refine risk assessment 1
• Document patient understanding and preference 1
• If patient accepts risks → May prescribe 75-100 mg daily 1

Common Pitfalls to Avoid

Do not prescribe aspirin based solely on diabetes diagnosis - recent trials show no benefit in diabetic patients without additional risk factors 2, 4

Do not ignore age >70 years as a contraindication - the ASPREE trial demonstrated increased mortality and bleeding without cardiovascular benefit in elderly patients 4, 6

Do not prescribe for "intermediate risk" without careful bleeding risk assessment - the ARRIVE trial showed no cardiovascular benefit but increased bleeding in intermediate-risk patients 4, 6

Do not use aspirin as a substitute for evidence-based therapies - statins and antihypertensives provide greater benefit with better safety profiles 1

Special Populations

Hypertensive Patients:

• Consider aspirin only if age ≥50 years with controlled BP (<150/90 mmHg), target organ damage, and 10-year CVD risk >15% 5
• Uncontrolled hypertension is an absolute contraindication 3

Alternative for Aspirin Allergy:

• Clopidogrel 75 mg daily may be used in documented aspirin allergy 5