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CLINICAL RESEARCH: INTERVENTIONAL CARDIOLOGY

Clopidogrel 600-Mg Double Loading Dose Achieves Stronger Platelet Inhibition Than Conventional Regimens

Results From the PREPAIR Randomized Study

Department of Medicine, Montreal Heart Institute and Université de Montréal, Montreal, Quebec, Canada.

Manuscript received August 3, 2007; revised manuscript received November 23, 2007, accepted December 2, 2007.

^_* Reprint requests and correspondence: Dr. Philippe L. L’Allier, Department of Medicine, Montreal Heart Institute, 5000 Belanger Street, Montreal, Quebec, Canada, H1T 1C8. (Email: philippe.lallier{at}icm-mhi.org).

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 µmol/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 µmol/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.

Abbreviations and Acronyms   ADP = adenosine diphosphate   Aggpeak = peak aggregation   Agg6min = late aggregation   PCI = percutaneous coronary intervention   PPP = platelet-poor plasma   PRP = platelet-rich plasma

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