What is the preferred antiplatelet therapy, Clopidogrel (Plavix) versus Ticagrelor (Brilinta), for patients with symptomatic Peripheral Artery Disease (PAD) and End-Stage Renal Disease (ESRD) on Peritoneal Dialysis (PD)?

Clopidogrel is Preferred Over Ticagrelor for Symptomatic PAD in ESRD Patients on PD

For patients with symptomatic Peripheral Artery Disease (PAD) and End-Stage Renal Disease (ESRD) on Peritoneal Dialysis (PD), clopidogrel 75 mg daily is the preferred antiplatelet therapy over ticagrelor. This recommendation is based on current guidelines and consideration of the unique risks in this specific patient population.

Rationale for Recommendation

Guideline Support for Clopidogrel in PAD

• The 2024 ACC/AHA/Multisociety PAD Guidelines recommend single antiplatelet therapy with either aspirin (75-100 mg daily) or clopidogrel (75 mg daily) for patients with symptomatic PAD 1.
• The 2024 ESC Guidelines for PAD specifically state that "the routine use of ticagrelor in patients with PAD is not recommended" 1.
• The ACCP Guidelines (Chest) provide a strong Grade 1A recommendation for clopidogrel 75 mg daily as a preferred antiplatelet therapy for secondary prevention in symptomatic PAD 1.

Special Considerations for ESRD Patients

• Patients with ESRD on dialysis have significantly higher bleeding risks compared to the general population.
• The K/DOQI Guidelines note that clopidogrel should be prescribed for patients with established atherosclerotic cardiovascular disease, which includes PAD 1.
• Patients with ESRD were not well represented in major trials establishing antiplatelet therapy benefits, suggesting caution when applying general population data 2.

Efficacy Comparison

• In the CAPRIE trial, clopidogrel showed a 24% relative risk reduction in cardiovascular events specifically in the PAD subgroup compared to aspirin 1.
• The EUCLID trial showed that ticagrelor had similar efficacy to clopidogrel in PAD patients, but with higher rates of adverse events 1, 3.
• A network meta-analysis confirmed that clopidogrel significantly decreases the risk of major adverse cardiovascular events compared with aspirin without increasing bleeding risk 4.

ESRD-Specific Concerns

• While ticagrelor may provide greater platelet inhibition in ESRD patients 5, this theoretical benefit must be balanced against:
  • Higher bleeding risk in ESRD patients
  • Higher cost of ticagrelor
  • Twice-daily dosing requirement (vs. once-daily for clopidogrel)
  • Lack of specific evidence showing superior outcomes in ESRD patients on PD

Clinical Algorithm for Antiplatelet Selection in PAD with ESRD

1. First-line therapy: Clopidogrel 75 mg daily

   • Well-established efficacy in PAD
   • Once-daily dosing improves adherence
   • Lower cost
   • Extensive clinical experience in ESRD patients

2. Alternative if clopidogrel contraindicated: Aspirin 75-100 mg daily

   • Consider if patient has history of clopidogrel hypersensitivity
   • Consider adding proton pump inhibitor for GI protection

3. When to avoid ticagrelor:

   • ESRD patients with history of dyspnea (common ticagrelor side effect)
   • Patients taking medications that interact with CYP3A4 inhibitors
   • Patients with compliance concerns (twice-daily dosing)
   • Patients with financial constraints

Important Caveats and Monitoring

• Monitor for bleeding complications, which are more common in ESRD patients
• Assess for drug interactions, particularly with other medications that affect platelet function
• Be aware that 50-80% of ESRD patients may have high on-treatment residual platelet reactivity with clopidogrel 2
• No routine platelet function testing is required for patients on clopidogrel 6
• For patients undergoing procedures, clopidogrel typically needs to be held for 5-7 days, whereas ticagrelor requires only 3-5 days

In conclusion, despite theoretical advantages of ticagrelor in terms of platelet inhibition, current guidelines and evidence support clopidogrel as the preferred antiplatelet agent for patients with symptomatic PAD and ESRD on peritoneal dialysis, primarily due to its established efficacy, once-daily dosing, lower cost, and acceptable safety profile in this high-risk population.