Background: Although platelet inhibition is key to successful percutaneous coronary intervention (PCI), the optimal loading dose of clopidogrel (Plavix) remains unknown. Studies have used doses up to 900 mg and various dosing schedules. L’Allier and colleagues performed a randomized study comparing three common clopidogrel loading regimens to determine the optimal level of platelet inhibition in patients undergoing elective angiography and PCI.

The Study: Patients admitted to a Canadian hospital for elective coronary angiography and PCI were eligible for the study. They were excluded if they had unstable angina, recent myocardial infarction or stroke, bleeding disorders, or severe liver disease, or were receiving anticoagulation therapy. Participants were randomly assigned to one of the following treatment regimens: (1) clopidogrel 300 mg the day before the procedure (at least 15 hours) and 75 mg on the morning of the procedure (Group A); (2) clopidogrel 600 mg the morning of (at least two hours before) the procedure (Group B); or (3) clopidogrel 600 mg the day before the procedure (at least 15 hours) and 600 mg the morning of (at least two hours before) the procedure (Group C). Blood was collected at randomization, immediately before the procedure, and on the morning after the procedure. Participants were assessed before hospital discharge and were contacted by telephone one month later about any adverse events.

The primary outcome was the inhibition of peak aggregation (Agg_peak) at the time of angiography. Other end points included inhibition of aggregation six minutes after the procedure (Agg_6min); the percentage of patients nonresponsive to therapy; significant hemorrhagic complications; and death, myocardial infarction, or target vessel revascularization within 30 days of the procedure.

Results: Diabetes was significantly more prevalent in the 49 patients in Group A and the 49 patients in Group B than the 50 patients in Group C. The three groups were well matched in all other relevant variables. The average age was 61 years, and the average left ventricular ejection fraction was 61 percent. Approximately 78 percent of participants in each group were men. In each group, more than 95 percent were taking aspirin; 78 to 88 percent used statins; more than one half used beta blockers; and 46 to 64 percent used angiotensin-converting enzyme inhibitors or angiotensin receptor agonists.

The baseline Agg_peak levels did not differ among the three groups. Platelet aggregation inhibition was significantly better in Group C than the other two groups. The inhibition of Agg_peak were 31.4, 29.0, and 49.5 percent in Groups A, B, and C, respectively. Comparisons between Groups A and B were not statistically significant. Similarly, differences in Agg_6min levels between Group C and the other groups were highly significant, but Groups A and B did not differ significantly. No patients in Group C were clopidogrel resistant, but nine patients in Group A and eight in Group B were. No major bleeding episodes, deaths, myocardial infarction, or revascularizations were recorded in the month of follow-up. Minor bleeding (mainly related to puncture sites) occurred in three Group A patients, eight Group B patients, and four Group C patients. No serious adverse effects or allergic reactions were noted during the study.

Conclusion: The authors conclude that significantly greater platelet inhibition results from clopidogrel 600 mg given the day before and the morning of the procedure.