In chronic kidney disease patients, is low‑dose aspirin recommended only for secondary cardiovascular prevention and not for primary prevention, especially when eGFR is below 30 mL/min/1.73 m² or bleeding risk is high?

Aspirin Use in Chronic Kidney Disease

In patients with CKD, aspirin should be reserved for secondary cardiovascular prevention only; avoid aspirin for primary prevention, particularly when eGFR is below 45 mL/min/1.73 m² or bleeding risk is elevated, as the increased bleeding risk outweighs uncertain cardiovascular benefit. 1

Guideline-Based Recommendations by CKD Stage and Indication

Secondary Prevention (Established CVD)

• Continue low-dose aspirin (75-162 mg daily) in CKD patients with prior myocardial infarction, stroke, or established coronary artery disease, as cardiovascular mortality reduction outweighs bleeding risk. 1, 2
• NICE, KDIGO, and ACC/AHA/ASA guidelines uniformly recommend aspirin for secondary prevention across all CKD stages, though with heightened caution about bleeding risk. 1
• This recommendation holds even in advanced CKD (eGFR <30 mL/min/1.73 m²) and dialysis-dependent patients when established atherosclerotic disease is present. 2

Primary Prevention (No Prior CVD)

• KDIGO and NICE guidelines explicitly state that aspirin is NOT indicated for primary prevention in CKD patients. 1
• ACC/AHA/ASA guidelines suggest aspirin may be considered for primary prevention only in the narrow window of eGFR 30-45 mL/min/1.73 m², but this is not a strong recommendation. 1
• For eGFR <30 mL/min/1.73 m², avoid aspirin for primary prevention entirely due to prohibitive bleeding risk without proven cardiovascular benefit. 1, 2

Evidence Supporting Guideline Recommendations

Primary Prevention Evidence

The most recent high-quality evidence comes from the TIPS-3 trial (2023), which showed aspirin reduced cardiovascular events in CKD patients with eGFR <60 mL/min/1.73 m² (HR 0.57,95% CI 0.34-0.94), but this benefit disappeared at higher eGFR levels. 3 However, this finding must be balanced against:

• A 2016 meta-analysis of 4,468 CKD patients found no statistically significant reduction in major cardiovascular events (RR 0.92,95% CI 0.49-1.73) but nearly doubled major bleeding risk (RR 1.98,95% CI 1.11-3.52). 1, 4
• The 2022 CRIC observational study of 3,664 CKD patients found aspirin was not associated with reduction in primary CVD events (HR 0.97,95% CI 0.77-1.23) or mortality. 5
• Current guidelines appropriately prioritize the meta-analysis showing harm over potential benefit, particularly given the high heterogeneity (I² = 71%) in cardiovascular outcomes. 1, 4

Bleeding Risk Quantification

• Major bleeding risk increases 2-fold (RR 2.04,95% CI 1.05-3.96) in CKD patients with eGFR <45 mL/min/1.73 m² taking aspirin. 1, 6
• Minor bleeding risk increases 2.7-fold (RR 2.70,95% CI 1.66-4.39) across all CKD stages. 1
• When aspirin is combined with anticoagulants, bleeding risk increases 3-6 fold, making combination therapy particularly hazardous in CKD. 6, 2

Practical Algorithm for Aspirin Decision-Making in CKD

Step 1: Determine Prevention Category

• Secondary prevention (prior MI, stroke, or established CAD): Proceed to Step 2
• Primary prevention (no prior CVD): Generally avoid aspirin; proceed to Step 3 only if eGFR 30-45 mL/min/1.73 m²

Step 2: Assess Bleeding Risk (for Secondary Prevention)

Aspirin is contraindicated if ANY of the following are present: 1, 6, 2

• Active bleeding or recent uncontrolled gastrointestinal bleeding
• Severe coagulopathy or disseminated intravascular coagulation
• Concurrent anticoagulant therapy (warfarin, DOACs)
• Aspirin allergy or clinically active hepatic disease
• Cirrhosis with ascites (absolute contraindication)

If no contraindications exist, prescribe aspirin 75-100 mg daily for secondary prevention regardless of eGFR level. 1, 2

Step 3: Primary Prevention in eGFR 30-45 mL/min/1.73 m² (Narrow Exception)

Only consider aspirin if ALL of the following criteria are met: 1, 3

• eGFR 30-45 mL/min/1.73 m²
• 10-year ASCVD risk ≥20%
• Age <70 years
• No bleeding risk factors (see Step 2)
• Patient preference after shared decision-making

For eGFR <30 mL/min/1.73 m², avoid aspirin for primary prevention entirely. 1, 2

Dosing and Monitoring

Optimal Dosing

• Use 75-100 mg daily; no dose adjustment is required for renal function. 1, 6, 2
• Doses above 100 mg increase bleeding risk without additional cardiovascular benefit. 2
• The UK-HARP-I trial used 100 mg daily, HOT trial used 75 mg daily, and JPAD trial used 81-100 mg daily, all showing similar efficacy. 1

Monitoring Requirements

• Establish baseline renal function (serum creatinine, eGFR) before initiating aspirin. 6
• Monitor for bleeding signs: gastrointestinal symptoms, bruising, epistaxis, melena. 6
• Check renal function periodically, particularly if other nephrotoxic medications are used. 6

Special Populations and Common Pitfalls

Dialysis-Dependent CKD (Stage 5D)

• Continue aspirin for secondary prevention in dialysis patients with established CAD. 2
• Never prescribe aspirin to prevent dialysis access thrombosis—a randomized trial was terminated early due to excessive GI bleeding without efficacy for preventing AV graft thrombosis. 7
• The DOPPS observational study showed aspirin increased MI risk (RR 1.21,95% CI 1.06-1.38) in hemodialysis patients without established CVD. 1

Emerging Evidence: Lipoprotein(a)

• A 2025 CRIC substudy found aspirin reduced MI by 38% (HR 0.62,95% CI 0.42-0.91) and ESRD by 28% (HR 0.72,95% CI 0.59-0.89) in CKD patients with Lp(a) ≥50 mg/dL, but not in those with lower Lp(a) levels. 8
• This represents hypothesis-generating data that may inform future guidelines, but current recommendations do not incorporate Lp(a) stratification. 8

Antiplatelet Resistance

• 50-80% of ESKD patients exhibit high on-treatment residual platelet reactivity (clopidogrel resistance), which may partially explain poorer aspirin efficacy in advanced CKD. 1
• This pharmacodynamic limitation further supports avoiding aspirin for primary prevention in advanced CKD. 1

Key Caveats

• The ongoing ATTACK trial (NCT03796156) is recruiting 25,210 CKD patients to definitively answer the primary prevention question; results are expected in 2025. 1, 9
• Until definitive trial data emerge, current guideline recommendations to avoid primary prevention aspirin in CKD remain reasonable and evidence-based. 1
• Do not discontinue aspirin solely because of declining renal function in patients with established CAD—the secondary prevention benefit persists across all CKD stages. 2
• Never combine aspirin with other NSAIDs in CKD patients, as this dramatically increases acute kidney injury risk. 2