There are conflicting opinions regarding the timing of steady state as it relates to dosing clopidogrel (Plavix) as well as the role of this agent in acute coronary syndrome and percutaneous coronary intervention (PCI). Studies show that a 300-mg loading dose should reach steady state (at 40%-50% platelet inhibition) within 14 hours and a 600-mg dose in about seven hours. Is this correct? How effective is this drug in the acute setting if a patient is likely to have an intervention within a couple of hours? Is clopidogrel intended to be an acute agent or a chronic agent that is more useful postintervention? — AMY L. RUTT, PA-C, Swoyersville, Pa.
The time frames you note are correct. Subsequent analysis of the Clopidogrel for the Reduction of Events During Observation (CREDO) trial revealed that clinical events were not significantly reduced compared with placebo unless 300 mg clopidogrel was given at least 15 hours prior to PCI. More rapid platelet inhibition is achieved with larger loading doses, and at least two to six hours is needed before adequate antiplatelet therapy is achieved. The Intracoronary Stenting and Antithrombotic Regimen-Rapid Early Action for Coronary Treatment (ISAR-REACT) trial looked at giving 600-mg loading doses at different time intervals prior to PCI. For low- to intermediate-risk patients, increasing the dosing interval beyond two to three hours did not yield an incremental benefit. Clopidogrel should be used prior to PCI and in higher-risk patients if pretreatment isn’t possible. Consider using platelet glycoprotein IIb/IIIa inhibition for more immediate antiplatelet effect during PCI. — Norma M. Keller, MD (145-9)