In an asymptomatic adult with elevated cholesterol (total 7.1 mmol/L, LDL‑C 4.7 mmol/L) and no history of cardiovascular disease, diabetes, or chronic kidney disease, should I start low‑dose aspirin for primary prevention?

Should You Start Aspirin for Primary Prevention?

No, you should not start aspirin for primary prevention in your case—an asymptomatic adult with elevated cholesterol but no established cardiovascular disease, diabetes, or chronic kidney disease. Contemporary guidelines have downgraded aspirin to a conditional recommendation (may be considered in highly selected cases only) because recent high-quality trials demonstrate that bleeding risk equals or exceeds cardiovascular benefit when patients receive modern statin and blood pressure therapy. 1

Why the Recommendation Has Changed

The 2019 ACC/AHA guidelines downgraded aspirin from routine use to a Class IIb recommendation (may be considered) based on three landmark 2018 trials—ASCEND, ARRIVE, and ASPREE—that collectively enrolled over 46,000 participants and showed that modest cardiovascular benefit was offset by increased major bleeding risk. 1 In unselected populations, the number needed to treat to cause a major bleed (210) is actually lower than the number needed to prevent an ASCVD event (265), indicating net harm. 1

Modern populations have lower baseline cardiovascular risk due to widespread statin use (34–75% in recent trials versus minimal use in older studies), improved blood pressure control, and reduced smoking rates—these factors make aspirin's absolute benefit smaller while bleeding risk remains unchanged. 1

When Aspirin Might Be Considered (Narrow Exceptions)

Aspirin may be considered only if you meet all of the following criteria simultaneously: 1

• Age 40–59 years
• Calculated 10-year ASCVD risk ≥10%
• Low bleeding risk (no history of GI bleeding, peptic ulcer, bleeding disorder, thrombocytopenia, concurrent NSAID use, anticoagulation, uncontrolled hypertension, chronic kidney disease, or age >70)
• Willingness for lifelong daily therapy
• At least one additional high-risk feature such as:
  • Current smoking
  • Strong family history of premature ASCVD
  • Inadequately controlled cholesterol despite therapy
  • Coronary artery calcium (CAC) score ≥100 2, 1
  • Chronic kidney disease with albuminuria
  • Markedly elevated lipoprotein(a) 2

Even when these criteria are met, shared decision-making is essential because the benefit-to-harm margin is narrow: treating 100 patients for 5–10 years prevents roughly one cardiovascular event while causing roughly one major bleeding event. 1

Coronary Artery Calcium Score as a Risk Stratifier

If you are considering aspirin and fall into the intermediate-risk category, CAC scoring is the preferred tool to guide the decision: 2, 1

• CAC = 0: Do not use aspirin—minimal atherosclerotic burden means very low near-term event risk even with elevated cholesterol. 1
• CAC ≥100: Aspirin (75–100 mg daily) may be considered after shared decision-making, as this score reflects significant coronary plaque burden and shifts the benefit-to-harm ratio favorably. 2, 1, 3
• CAC 1–99: Evidence is mixed; generally aspirin is not recommended unless multiple additional high-risk features are present. 3

Multiple international societies (ACC/AHA, ESC, NLA) endorse CAC as the preferred risk-stratification tool when uncertainty remains after initial ASCVD risk calculation. 2

Absolute Contraindications to Aspirin

Do not use aspirin if you have any of the following: 1

• Prior gastrointestinal bleeding or active peptic ulcer disease
• Known bleeding disorder or thrombocytopenia
• Severe liver disease
• Concurrent anticoagulation (warfarin or DOACs)
• Regular NSAID use
• Uncontrolled hypertension
• Chronic kidney disease (increases bleeding risk)
• Age >70 years

Age-Specific Guidance

• Age 40–59 years with ≥10% 10-year ASCVD risk: Aspirin may be considered only in highly selected patients meeting all criteria above. 1, 4
• Age 60–70 years: Aspirin should generally not be initiated; the 2022 USPSTF statement concludes with moderate certainty that there is no net benefit (Grade D). 1, 4
• Age >70 years: Aspirin should not be used for primary prevention—the ASPREE trial showed increased bleeding and mortality without cardiovascular benefit, with extended follow-up reporting higher major adverse cardiovascular events (HR 1.17) and persistent bleeding risk (HR 1.24). 1

Special Populations

Diabetes

Aspirin is not routinely recommended for primary prevention in patients with diabetes. 2, 1 The ASCEND trial (15,480 diabetic participants without prior ASCVD) showed only a 12% relative reduction in serious vascular events (8.5% vs 9.6%) but a 29% relative increase in major bleeding (4.1% vs 3.2%). 1 For diabetic individuals ≥50 years with at least one additional major cardiovascular risk factor (family history of premature ASCVD, hypertension, dyslipidemia, smoking, or chronic kidney disease), aspirin may be considered only after shared decision-making and if bleeding risk is low. 2, 1

Familial Hypercholesterolemia

In asymptomatic patients with familial hypercholesterolemia at higher risk of ASCVD (those with markedly elevated lipoprotein(a), diabetes, or adverse findings on cardiovascular imaging), low-dose aspirin may be considered as a primary prevention measure provided there are no bleeding contraindications. 2

What You Should Do Instead

Your priority should be aggressive lipid management, not aspirin. With total cholesterol 7.1 mmol/L (274 mg/dL) and LDL-C 4.7 mmol/L (182 mg/dL), you meet criteria for statin therapy: 2

• Initiate maximally tolerated high-potency statin (atorvastatin, rosuvastatin, or pitavastatin) with target LDL-C <100 mg/dL (2.6 mmol/L) if you have ≥2 risk factors. 2
• If LDL-C goal is not achieved after 12 weeks of therapeutic lifestyle changes and statin therapy, add ezetimibe and/or bempedoic acid. 2
• Therapeutic lifestyle changes include: <7% of calories from saturated fat, cholesterol <200 mg/day, increased viscous fiber (10–25 g/day), plant stanols/sterols (up to 2 g/day), weight reduction, and at least 30 minutes of moderate-intensity physical activity on most days. 2

Common Pitfalls to Avoid

• Do not prescribe aspirin automatically based solely on a 10% 10-year ASCVD risk threshold—contemporary trials show an unfavorable risk-benefit ratio at this cutoff without additional high-risk features. 1
• Do not rely solely on calculated ASCVD risk—the pooled cohort equations tend to overestimate actual risk in contemporary populations receiving optimal statin and blood-pressure therapy. 1
• Do not exceed 100 mg daily aspirin dose for primary prevention—higher doses have not shown additional cardiovascular benefit and increase bleeding risk. 1, 5
• Gastrointestinal bleeding risk in real-world settings may be as high as 5 per 1,000 person-years—this risk must be incorporated into net-benefit calculations. 1

When Aspirin IS Strongly Indicated

Aspirin 75–162 mg daily (most commonly 81 mg in the U.S.) remains strongly recommended for all patients with established ASCVD (history of myocardial infarction, stroke, coronary revascularization, or documented coronary artery disease), where the benefit substantially outweighs bleeding risk. 1, 5, 6