Objectives: This study was designed to evaluate the effects of long-term clopidogrel and aspirin administration on platelet aggregation, activation, and inflammation.
Background: Clopidogrel resistance was described in 15% to 30% of patients with short-term therapy, but its antiplatelet effects with long-term therapy is unknown.
Methods: We performed a prospective study of patients undergoing coronary stenting who were on aspirin for > or =5 days but not previously on clopidogrel. Clopidogrel 600 mg was given before stenting. Clopidogrel 75 mg/day and aspirin 325 mg/day were continued for 1 year. Light-transmittance aggregometry with 5-micromol/l adenosine diphosphate and 1-mmol/l arachidonic acid stimulation; VerifyNow clopidogrel and aspirin assays; platelet activation receptor expression of CD40L, CD62P, and PAC-1 (antibody against activated glycoprotein IIb/IIIa); and inflammatory markers of soluble CD40L and P-selectin, high-sensitivity C-reactive protein, interleukin-10, and interleukin-18 were measured at baseline; 1 day; and 1, 6, and 12 months. Our primary analysis compared light-transmittance aggregometry aggregation at 1 versus 12 months.
Results: We enrolled 26 patients who completed a 1-year follow-up. Maximal platelet adenosine diphosphate-stimulated aggregation was 61.8 +/- 25.9% at baseline, 22.1 +/- 18.3% at 1 day, 30.6 +/- 16.8% at 1 month, 29.0 +/- 13.3% at 6 months, and 26.7 +/- 13.6% at 12 months (p = 0.099 for 12 months vs. 1 month). VerifyNow clopidogrel platelet inhibition was similar at 12 months versus 1 month (38.9 +/- 19.7% vs. 45.6 +/- 26.7%, p = 0.578). Likewise, there was no difference in aspirin's effects on platelet aggregation at 12 months versus 1 month. In contrast, platelet activation receptor expression of CD40L, CD62P, and PAC-1 were higher at 12 months versus 1 month.
Conclusions: Our pilot study showed no attenuation of clopidogrel's effects on platelet aggregation with long-term administration. However, platelet activation receptor expression increased with time and should be further evaluated.