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

Author(s): L'Allier PL, Ducrocq G, Pranno N, Noble S, Ibrahim R, Gregoire JC, Azzari F, Nozza A, Berry C, Doucet S, Labarthe B, Theroux P, Tardif JC, PREPAIR Study Investigators

Affiliation(s): Department of Medicine, Montreal Heart Institute and Universite de Montreal, Montreal, Quebec, Canada. philippe.lallier@icm-mhi.org

Publication date & source: 2008-03-18, J Am Coll Cardiol., 51(11):1066-72.

Publication type: Research Support, Non-U.S. Gov't

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 (>or=15 h) + 75 mg the morning of the procedure; Group B, clopidogrel 600 mg the morning of the procedure (>or=2 h); and Group C, clopidogrel 600 mg the day before (>or=15 h) and 600 mg the morning of the procedure (>or=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 micromol/l adenosine diphosphate; p < 0.0001) and 54.1%, 57.7%, and 81.1%, respectively, for late aggregation (p < 0.0001). Similar striking reductions were observed when 20 micromol/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.