Coronary artery disease
Influence of Aspirin Resistance on Platelet Function Profiles in Patients on Long-Term Aspirin and Clopidogrel After Percutaneous Coronary Intervention

https://doi.org/10.1016/j.amjcard.2005.07.106Get rights and content

Increased platelet inhibition is achieved when clopidogrel is added to aspirin (acetylsalicylic acid [ASA]). A broad variability in platelet inhibition profiles during the early phases of treatment has been demonstrated and may be attributed to ASA resistance. However, the influence of ASA sensitivity on platelet function profiles of patients on long-term dual antiplatelet therapy has yet to be explored. A total of 135 patients who had previously undergone percutaneous coronary intervention on long-term (>1 month) ASA and clopidogrel therapy was included. The PFA-100 system was used to define ASA resistance. Platelet aggregation, after adenosine diphosphate (6 and 20 μmol/L) and collagen (6 μg/ml) stimuli, and platelet activation (glycoprotein IIb/IIIa activation and P-selectin expression), after adenosine diphosphate (2 μmol/L) and thrombin receptor-activating peptide (50 μmol/L) stimuli, were assessed by light transmittance aggregometry and flow cytometry, respectively. Patient variability in response to treatment was defined by the coefficient of variability. ASA resistance was found in 60 of 135 patients (44%). Patients with diabetes were more frequently ASA resistant. Collagen/epinephrine- and collagen/adenosine diphosphate-coated cartridges on the PFA-100 had shorter closure times in the ASA-resistant population compared with ASA-sensitive patients. Platelet aggregation and activation were significantly higher in ASA-resistant patients. A broad variability (coefficient of variation >0.25) in patient response to treatment was observed in ASA-resistant and -sensitive patients. In conclusion, ASA resistance is associated with increased platelet reactivity in patients on long-term dual antiplatelet treatment.

Section snippets

Study population

A total of 135 patients who had previously undergone elective percutaneous coronary intervention and were on ASA (100 mg/day) and clopidogrel (75 mg/day) therapy for ≥1 month were included. Patients were screened during their routine clinical follow-up visits at our outpatient clinic. All patients were clinically stable after percutaneous coronary intervention. Patient compliance to antiplatelet treatment was assessed by interview and pill counting. Patients were enrolled consecutively if these

Results

In the overall study population, 60 of 135 patients (44%) were ASA resistant and 75 (56%) were ASA sensitive. The rate of ASA resistance was even higher among diabetics (57%). The characteristics of ASA-resistant and -sensitive patients are shown in Table 1. No differences were observed between groups, except for a higher number of diabetic patients in the ASA-resistant group (p = 0.001).

Hematocrit, platelet count, and mean platelet volume values were similar between the groups (Table 1).

Discussion

This is the first study to investigate the influence of ASA resistance on platelet function profiles of patients concomitantly treated with clopidogrel. In particular, ASA-resistant patients showed increased platelet activation and aggregation compared with ASA-sensitive patients, regardless of the concomitant use of clopidogrel. In addition, the results of the present study also demonstrated the presence of a significant patient variability in platelet response in ASA-resistant and -sensitive

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