Timing, dosing and length of clopidogrel therapy
In the light of more recent results on the use of a 600 mg loading dose, 10-12 the authors of this analysis concluded that pretreatment with a 300 mg loading dose should be given at least 15-24 hours before the intervention and, if such long pretreatment period is not possible, pretreatment with 600 mg should be used at least 2 hours before PCI. 9
Pretreatment with a 600 mg loading dose Platelet function studies have shown that, in contrast to administration of a 300 mg loading dose of clopidogrel, administration of a 600 mg loading dose results in platelet function inhibition similar to that achieved with chronic therapy within 2 hours. 13,14 In a randomized (albeit small) trial, administration of a 600 mg loading dose significantly reduced the incidence of periprocedural MI in patients treated with PCI as compared with administration of a 300 mg loading dose. 15 Moreover, the results of the ISARREACT (Intracoronary Stenting and Antithrombotic Regimen-Rapid Action for Coronary Treatment) trial are highly suggestive for a benefit resulting from pretreatment with a 600 mg loading dose in low-to intermediate-risk patients. 10 In this double-blind randomized trial including 2159 patients, it was tested whether administration of the GPIIb/IIIa antagonist abciximab reduces the incidence of ischemic complications in patients undergoing elective stent placement after pretreatment with a 600 mg loading dose of clopidogrel at least 2 hours before the intervention. The composite endpoint (death, MI, and urgent target-vessel revascularization at 30 days after PCI) was reached in 4%
coronary disease prior to cardiac catheterization (20 patients treated with 300, 600, and 900 mg, respectively). 22 In this trial, ADP-induced platelet aggregation was assessed before and 4 hours after administration of clopidogrel. In addition, clopidogrel and its metabolites (the active thiol metabolite and the carboxyl metabolite that lacks any antiplatelet activity) were measured before and serially after administration of clopidogrel. The main results of this trial were that administration of a 600 mg loading dose results in more intense inhibition of platelet aggregation than administration of a 300 mg loading dose and that no further significant inhibition of platelet aggregation can be achieved with administration of a single 900 mg dose ( Figure 6.3 ).