What are the guidelines for using low-dose aspirin (acetylsalicylic acid) in patients with Chronic Kidney Disease (CKD) stage 4?

Low-Dose Aspirin Use in CKD Stage 4

Low-dose aspirin is generally not recommended for primary prevention in CKD stage 4 patients due to increased bleeding risk without clear cardiovascular benefit, but it should be used for secondary prevention in those with established cardiovascular disease. 1

Primary vs. Secondary Prevention Guidelines

Primary Prevention (No Existing Cardiovascular Disease)

• Current guidelines recommend avoiding aspirin for primary prevention in CKD patients, including those with stage 4 disease 1
• The KDIGO 2024 guidelines do not support aspirin use for primary prevention in CKD 1
• The risk-benefit ratio is unfavorable due to:
  • Nearly doubled risk of major bleeding (RR 2.04; 95% CI 1.05-3.96) 1
  • No statistically significant reduction in major cardiovascular events (RR 0.92; 95% CI 0.49-1.73) 2

Secondary Prevention (Existing Cardiovascular Disease)

• KDIGO 2024 strongly recommends oral low-dose aspirin for secondary prevention in CKD patients with established ischemic cardiovascular disease (Grade 1C) 1
• Multiple guidelines (NICE, KDIGO, ACC/AHA/ASA) consistently support aspirin for secondary prevention in CKD 1

Evidence Analysis

Bleeding Risk Considerations

• CKD stage 4 patients have significantly increased bleeding risk with antiplatelet therapy:
  • Major bleeding risk increases progressively with worsening kidney function 3
  • CKD stage 4 patients had 6.1% risk of major bleeding within the first month of antiplatelet therapy compared to 3.4% in those with normal kidney function 3
  • Meta-analysis showed aspirin nearly doubled the risk of major bleeding events in CKD (RR 1.98; 95% CI 1.11-3.52) 2

Cardiovascular Benefit Evidence

• The Hypertension Optimal Treatment trial suggested a potential 66% relative risk reduction in major cardiovascular events for patients with eGFR <45 ml/min/1.73m² 1
• However, this finding was not consistent across studies, with a meta-analysis showing no statistically significant reduction in cardiovascular events 2
• The AASER study suggested potential benefits for coronary events and renal outcomes, but was limited by small sample size 4

Special Considerations for CKD Stage 4

• Concomitant medications: Avoid combining aspirin with other medications that increase bleeding risk when possible 1
• Dose: If aspirin is indicated for secondary prevention, use the lowest effective dose (75-100 mg daily) 1
• Monitoring: Regular assessment for bleeding complications is essential, especially gastrointestinal bleeding 5
• Alternative antiplatelet agents: Consider P2Y12 inhibitors when there is aspirin intolerance 1

Ongoing Research

The Aspirin To Target Arterial Events in Chronic Kidney Disease (ATTACK) trial is currently investigating daily aspirin for primary prevention in CKD patients (excluding stage 5/dialysis). Results are expected in 2025 and may provide more definitive guidance 1, 6.

Clinical Decision Algorithm

1. Determine if patient has established cardiovascular disease:

   • If YES (secondary prevention) → Prescribe low-dose aspirin (75-100 mg daily)
   • If NO (primary prevention) → Generally avoid aspirin

2. For primary prevention cases, assess individual risk factors:

   • Very high cardiovascular risk + low bleeding risk → Consider aspirin on case-by-case basis
   • Any significant bleeding history → Avoid aspirin
   • Concomitant use of other medications increasing bleeding risk → Avoid aspirin

3. For secondary prevention cases with high bleeding risk:

   • Consider gastroprotection with proton pump inhibitors
   • Monitor closely for bleeding complications
   • Consider alternative antiplatelet therapy if aspirin is contraindicated

Remember that the risk of bleeding increases substantially in CKD stage 4, and the evidence for cardiovascular benefit in primary prevention remains insufficient to outweigh this risk.