Impaired responsiveness to clopidogrel and aspirin in patients with recurrent stent thrombosis following percutaneous intervention for peripheral artery disease

Abstract

Patients with peripheral artery disease (PAD) following peripheral percutaneous transluminal angioplasty (PTA) with stent implantation are prone to stent thrombosis despite treatment with aspirin and clopidogrel. Impaired clopidogrel responsiveness is associated with increased risk of ischemic events in patients following coronary stent implantation. We sought to assess platelet responsiveness to clopidogrel and aspirin in patients with PAD and recurrent stent thrombosis. Platelet aggregation induced by 5 and 20 µmol/l adenosine diphosphate (ADP) and 0.5 mmol/l arachidonic acid (AA), together with platelet reactivity index (PRI) and serum thromboxane B(2) (TXB(2)), were determined in 11 patients with PAD and a history of stent thrombosis (mean, 3.1 ± 1.14) after PTA and in 15 patients with PAD with no such history, also in 11 controls with coronary artery disease (CAD) and previous stent thrombosis. Platelet aggregation to 5 µmol/l ADP was higher in subjects with PAD and stent thrombosis than in those without stent thrombosis (p = 0.0003) and CAD subjects (p = 0.002). Aggregation induced by 20 µmol/l ADP was higher in PAD group with stent thrombosis than in PAD subjects without thrombosis (p = 0.004). The PAD group with stent thrombosis had higher AA-induced platelet aggregation than CAD controls (p = 0.007) and serum TXB(2) concentrations higher than PAD group without thrombosis (p = 0.002) and CAD group (p = 0.02). Concluding, platelet responsiveness to clopidogrel and aspirin is impaired in patients with PAD and recurrent stent thrombosis following PTA, as compared with similar individuals with CAD, and PAD with no history of stent thrombosis. This indicates that atherosclerosis burden affects platelet function and might contribute to stent thrombosis following percutaneous intervention in peripheral arteries.

Review of aspirin and clopidogrel resistance in peripheral arterial disease

“…15 A 2013 study involving patients with PAD (26 patients) and CAD (11 patients) taking aspirin and clopidogrel compared platelet function in PAD patients with recurrent peripheral stent thrombosis, PAD patients without stent thrombosis, and CAD patients with a history of stent thrombosis. 14 On platelet function assays, the PAD patients with stent thrombosis had significantly higher AA-induced platelet aggregation compared with the CAD group (P ¼ .007) and higher thromboxane B 2 compared with the nonstent thrombosis PAD patients (P ¼ .002), indicative of a poorer response to aspirin compared to the other two groups. This demonstrated that AR is higher among PAD patients with stent thrombosis compared with both CAD patients with stent thrombosis and PAD patients without stent thrombosis, highlighting the propensity for adverse vascular events in patients with resistance to aspirin.…”

“…This demonstrated that AR is higher among PAD patients with stent thrombosis compared with both CAD patients with stent thrombosis and PAD patients without stent thrombosis, highlighting the propensity for adverse vascular events in patients with resistance to aspirin. 14,15 A study of 50 PAD patients taking 100 mg of aspirin found that 18% of patients were AR. Increasing aspirin dose to 300 mg improved platelet inhibition on PFA in 44% of affected patients, although platelet inhibition was not maximal.…”

“…[11][12][13] More recently, there appears to be an emerging, limited body of literature analyzing a relationship between AR and CR and ischemic events in PAD. [14][15][16] However, almost all studies and reviews into AR or CR in PAD analyze only one antiplatelet in isolation rather than both. 16,17 Current research shows that more and more PAD patients are being treated with dual antiplatelet therapy.…”

Antiplatelet Therapy for Peripheral Arterial Disease and Critical Limb Ischemia

“…Additionally, patients with stent thrombosis had higher serum arachidonic acid and thromboxane B2 levels. 50…”

Assessment of platelet function and resistance to aspirin and clopidogrel in patients with peripheral arterial disease undergoing percutaneous transluminal angioplasty

“…in patients who underwent stent implantation into peripheral arteries [7,8]. Despite the use of such therapy, adverse events, including stent thrombosis, are still observed [2,7,9,10]. In patients with PAD, there is a tendency to increased platelet activity, which may be resistant to the antiplatelet effect of ASA [11,12].…”