Clopidogrel 600-mg double loading dose achieves stronger platelet inhibition than conventional regimens -: Results from the PREPAIR randomized study

Objectives The objective of this study was to compare the level of platelet inhibition achieved by 3 different clopidogrel loading regimens in patients undergoing elective angiography and percutaneous coronary intervention when appropriate. Background Optimal platelet inhibition is a key therapeutic goal for patients undergoing percutaneous coronary intervention. Although 600 mg has been described as the maximum absorbed dose when given as a single bolus, the effects of 2 boluses given 24 h apart have not been described. Methods Patients (n = 148) were randomly assigned to one of 3 regimens: Group A, clopidogrel 300 mg the day before (>= 15 h) + 75 mg the morning of the procedure; Group B, clopidogrel 600 mg the morning of the procedure (>= 2 h); and Group C, clopidogrel 600 mg the day before (>= 15 h) and 600 mg the morning of the procedure (>= 2 h). Blood samples were obtained at baseline and immediately before angiography. Peak and late platelet aggregation were measured in platelet rich plasma, with researchers blinded to treatment allocation. Results There was a consistent difference favoring Group C in all aggregation parameters. Percent inhibition in Groups A, B, and C was 31.4%, 29.0%, and 49.5%, respectively, for peak aggregation (5 mu mol/l adenosine diphosphate; p < 0.0001) and 54.1%, 57.7%, and 811%, respectively, for late aggregation (p < 0.0001). Similar striking reductions were observed when 20 mu mol/l adenosine diphosphate was used. All comparisons between Group C and the other 2 groups were statistically significant, and those between Groups A and B were not. Conclusions Clopidogrel 600-mg double bolus achieves greater platelet inhibition than conventional single loading doses.