What is the role of low-dose aspirin (acetylsalicylic acid) in patients with chronic kidney disease (CKD), particularly those with a history of hypertension, diabetes, or cardiovascular disease?

Role of Low-Dose Aspirin in Chronic Kidney Disease

Primary Prevention: Generally Not Recommended

Low-dose aspirin should NOT be routinely used for primary prevention of cardiovascular disease in patients with CKD, as current evidence shows no significant cardiovascular benefit while substantially increasing bleeding risk. 1, 2

Evidence Against Primary Prevention

• Meta-analysis of primary prevention trials in CKD patients (n=7,852) demonstrated no statistically significant reduction in cardiovascular events (HR 0.76,95% CI 0.54-1.08), all-cause mortality (HR 0.94), coronary heart disease (HR 0.66), or stroke (HR 0.87) 2

• Major bleeding events increased by approximately 50% (HR 1.53,95% CI 1.13-2.05) and minor bleeding events more than doubled (HR 2.64,95% CI 1.64-4.23) with aspirin use 2

• The Hypertension Optimal Treatment trial showed near doubling of major bleeding risk (RR 2.04,95% CI 1.05-3.96) in CKD patients without significant stroke reduction 1

Limited Exception for Moderate CKD

• ACC/AHA guidelines suggest aspirin may be considered for primary prevention only in patients with GFR 30-45 ml/min who have additional high-risk features, though this remains controversial 1

• This recommendation predates recent negative trial data and should be applied with extreme caution 1

Harmful Effects in Advanced CKD

• In predialysis advanced CKD patients with anemia, aspirin use was associated with 15% increased risk of entering dialysis (HR 1.15,95% CI 1.10-1.21) and 46% increased risk of death before dialysis (HR 1.46,95% CI 1.25-1.71) 3

• Patients with low body weight (<60 kg) showed particularly increased cardiovascular event risk with aspirin (HR 4.014) 4

Secondary Prevention: Recommended with Caution

Low-dose aspirin SHOULD be used for secondary prevention in all CKD patients with established ischemic cardiovascular disease (prior MI, stroke, or coronary revascularization), as cardiovascular benefits outweigh bleeding risks in this specific population. 1, 5

Guideline Consensus

• NICE, KDIGO, and ACC/AHA all recommend aspirin for secondary prevention in CKD, though with explicit caution about increased bleeding risk 1

• This recommendation applies across all CKD stages including stage 4 (GFR 15-29 ml/min), but requires careful bleeding risk assessment 1, 5

Alternative Antiplatelet Agents

• If aspirin is not tolerated, switch to P2Y12 inhibitors (clopidogrel or ticagrelor) 5

• However, avoid P2Y12 inhibitors in CKD stage 5 (eGFR <15 ml/min) due to insufficient safety data 5

• Be aware that 50-80% of ESKD patients demonstrate clopidogrel resistance, though clinical significance remains uncertain 1, 5

Dialysis-Dependent Patients

For patients on hemodialysis or peritoneal dialysis, aspirin should only be continued if already prescribed for documented secondary prevention; do not initiate aspirin for primary prevention in dialysis patients. 1

• The bleeding risk is particularly elevated in dialysis-dependent CKD without clear cardiovascular benefit for primary prevention 1

• Platelet dysfunction is already present due to uremia, making additional antiplatelet therapy more hazardous 6

Monitoring and Safety Considerations

Bleeding Risk Assessment

• Monitor renal function (eGFR, serum creatinine) at baseline, 1-2 weeks after initiating aspirin, then every 3-6 months 5

• Increase monitoring frequency when clinical circumstances change or when adding medications that affect coagulation 5, 7

• Assess for history of gastrointestinal bleeding, peptic ulcer disease, or concurrent use of medications that increase bleeding risk (NSAIDs, anticoagulants) 1

Absolute Contraindications

• Never prescribe NSAIDs or COX-2 inhibitors concurrently with aspirin in CKD patients due to compounded risks of acute kidney injury, worsened heart failure, and exacerbated platelet dysfunction 5

• Use acetaminophen at conservative doses for pain management instead 5

• Avoid combining aspirin with anticoagulants unless absolutely necessary for specific indications (e.g., mechanical heart valve with atrial fibrillation) 5

Common Pitfalls to Avoid

• Do not assume all CKD patients are at uniformly high cardiovascular risk - use validated risk prediction tools like the UK Prospective Diabetes Study Risk Engine or ARIC CHD Risk Calculator to stratify risk 1

• Do not empirically withhold aspirin in patients with documented prior MI, stroke, or coronary revascularization - the secondary prevention benefit is established even with increased bleeding risk 5, 7

• Do not prescribe aspirin for primary prevention in younger CKD patients (men <50 years, women <60 years) without additional major cardiovascular risk factors, as bleeding risks clearly outweigh benefits 1

• Do not continue aspirin during active bleeding episodes - immediately discontinue all antiplatelet therapy until bleeding is controlled 6

Ongoing Research

• The ATTACK trial (Aspirin To Target Arterial Events in Chronic Kidney Disease) is currently recruiting 25,210 CKD patients (stages G1-G4, excluding stage 5 and dialysis) to definitively assess aspirin for primary prevention, with results anticipated in 2025 1, 8

• Until these results are available, current guideline recommendations against routine primary prevention remain appropriate 1