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Response to clopidogrel in patients undergoing lower extremity revascularization
Michael Tawil1, Thomas S Maldonado2, Yuhe Xia3
1Leon H. Charney Division of Cardiology, Department of Medicine, New York University Grossman School of Medicine, New York, NY, USA.
Insights
Higher platelet aggregation in patients on clopidogrel increases the risk of major adverse limb events (MALE) after lower extremity revascularization. Poor response to clopidogrel is linked to a greater MALE incidence.
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.
Objectives:
Clopidogrel is effective at decreasing cardiovascular events in patients with peripheral artery disease (PAD); however, its effect on limb outcomes are less known. This study investigated the variability in response to clopidogrel and its relationship with clinical limb outcomes.
Methods:
Three hundred subjects were enrolled in the Platelet Activity and Cardiovascular Events (PACE) study prior to lower extremity revascularization, of whom 104 were on clopidogrel. Light transmission platelet aggregation was measured in response to ADP 2 m immediately prior to revascularization. Patients were followed longitudinally for a median follow-up of 18 months. The primary endpoint was major adverse limb events (MALE) defined by major amputation or reoperation of the affected limb. Patients were stratified into groups according to percent ADP-induced aggregation. Poor response to clopidogrel was defined by >50% aggregation.
Results:
Overall, the median age was 70 (63, 76) and 35.6% were female. Twenty-nine (27.9%) patients experienced MALE during their follow-up. Median aggregation to ADP 2 m was 22.5% (Q1-Q3: 10%, 50%) and 27 subjects (26%) were clopidogrel poor responders. Baseline aggregation was higher in subjects who went on to develop a MALE than those without MALE (43% vs 20%, p = .017). Subjects with aggregation > median (22.5%) were more likely to experience MALE than aggregation < median (38.5% vs 17.3%, p = .029). After multivariable adjustment for age, sex, race/ethnicity, BMI, diabetes, coronary artery disease, and aspirin use, aggregation > median was associated with MALE (adjusted HR [aHR] 2.67, 95% CI 1.18-6.01, p = .018). When stratified by established cut-offs for responsiveness to clopidogrel (50% aggregation), poor responders were more likely to experience MALE than normal responders (44.4% vs 22.1%, aHR 2.18, 95% CI 1.00-4.78, p = .051).
Conclusions:
Among patients undergoing lower extremity revascularization on clopidogrel, higher baseline percent aggregation is associated with increased risk for major adverse limb events.
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