Clopidogrel resistance: Role of body mass and concomitant medications

Introduction: Platelets have a central role in the development of arterial thrombosis and subsequent cardiovascular events. An appreciation of this has made antiplatelet therapy the cornerstone of cardiovascular disease management. Recent studies have described the phenomenon of clopidogrel resistance but the possible mechanisms are still unclear. Patients and methods: The aim of this study was to compare the characteristics (risk profile, previous diseases, medications, hemorheological variables and plasma von Willebrand factor and soluble P-selectin levels) of patients in whom clopidogrel provided effective platelet inhibition with those in whom clopidogrel was not effective in providing platelet inhibition. 157 patients with chronic cardio- and cerebrovascular diseases (83 males, mean age 61 +/- 11 yrs, 74 females, 63 +/- 13 yrs) taking 75 mg clopidogrel daily (not combined with aspirin) were included in the study. Results: Compared with clopidogrel-resistant patients (35 patients (22%), patients who demonstrated effective clopidogrel inhibition had a significantly lower BMI (26.1 vs. 28.8 kg/m(2), p < 0.05). Patients with ineffective platelet aggregation were significantly more likely to be taking benzodiazepines (25% vs. 10%) and selective serotonin reuptake inhibitors (28% vs. 12%) ( p < 0.05). After an adjustment to the risk factors and medications BMI (OR 2.62; 95% CI: 1.71 to 3.6; p < 0.01), benzodiazepines (OR 5.83; 95% CI: 253 to 7.1; p < 0.05) and SSRIs (OR 5.22; 95% CI: 2.46 to 6.83; p < 0.05) remained independently associated with CLP resistance. There was no significant difference in the rheological parameters and in the plasma levels of adhesive molecules between the two examined groups. Conclusion: The background of ineffective clopidogrel medication is complex. Drug interactions may play a role on clopidogrel bioavailability, on the other hand, the significant difference in BMI between the two examined groups suggests that clopidogrel therapy should be weight-adjusted. (c) 2006 Elsevier Ireland Ltd. All rights reserved.