Response to clopidogrel in patients undergoing lower extremity revascularization

Area of Science:

• Vascular Surgery
• Pharmacology
• Cardiology

Background:

• Clopidogrel is vital for reducing cardiovascular events in peripheral artery disease (PAD).
• Its impact on limb-specific outcomes in PAD patients remains less understood.
• Understanding clopidogrel response variability is crucial for managing limb outcomes.

Purpose of the Study:

• To investigate clopidogrel response variability in patients undergoing lower extremity revascularization.
• To determine the relationship between clopidogrel responsiveness and clinical limb outcomes.
• To assess the risk of major adverse limb events (MALE) based on platelet aggregation levels.

Main Methods:

• The Platelet Activity and Cardiovascular Events (PACE) study enrolled 300 subjects prior to lower extremity revascularization.
• Light transmission platelet aggregation was measured in response to ADP in 104 clopidogrel-treated patients.
• Patients were followed for 18 months, with MALE defined as major amputation or reoperation; poor response was >50% aggregation.

Main Results:

• 27.9% of patients experienced MALE. Higher baseline aggregation was observed in patients who developed MALE (43% vs 20%, p=.017).
• Patients with aggregation above the median (22.5%) had a higher MALE likelihood (38.5% vs 17.3%, p=.029).
• High aggregation (>median) was associated with MALE (aHR 2.67), and poor responders (>50% aggregation) had increased MALE risk (aHR 2.18).

Conclusions:

• Elevated baseline platelet aggregation in patients on clopidogrel undergoing lower extremity revascularization correlates with a higher risk of MALE.
• Poor responders to clopidogrel exhibit a significantly increased risk for MALE.
• Assessing clopidogrel response may aid in stratifying MALE risk in PAD patients.