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. 2023 Dec;31(6):1110-1116.
doi: 10.1177/17085381221103417. Epub 2022 May 19.

Response to clopidogrel in patients undergoing lower extremity revascularization

Michael Tawil  1 , Thomas S Maldonado  2 , Yuhe Xia  3 , Todd Berland  2 , Neal Cayne  2 , Glenn Jacobowitz  2 , Joanelle Lugo  2 , Patrick Lamparello  2 , Mikel Sadek  2 , Caron Rockman  2 , Jeffrey S Berger  1   2   4
Affiliations

Response to clopidogrel in patients undergoing lower extremity revascularization

Michael Tawil et al. Vascular. 2023 Dec.

Abstract

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 μm 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 μ 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.

Keywords: clopidogrel; peripheral artery disease; platelets; revascularization.

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Conflict of interest statement

Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
Percent aggregation to (a) ADP 2.0 μM and (b) arachidonic acid 1600 μM in patients with and without an incident major adverse limb event.
Figure 2.
Figure 2.
MALE incidence in subjects with (a) platelet aggregation greater than 22.5% (median aggregation) and (b) platelet aggregation greater than 50%.
See this image and copyright information in PMC

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